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The incidence of co-morbidities related to obesity and overweight: A systematic review and meta-analysis Guh, Daphne P; Zhang, Wei; Bansback, Nick; Amarsi, Zubin; Birmingham, C L; Anis, Aslam H Mar 25, 2009

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ralssBioMed CentBMC Public HealthOpen AcceResearch articleThe incidence of co-morbidities related to obesity and overweight: A systematic review and meta-analysisDaphne P Guh1, Wei Zhang1, Nick Bansback1, Zubin Amarsi1, C Laird Birmingham1,2 and Aslam H Anis*1,3Address: 1Centre for Health Evaluation and Outcome Sciences, St Paul's Hospital, Vancouver, BC, Canada, 2Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada and 3School of Population and Public Health, University of British Columbia, Vancouver, BC, CanadaEmail: Daphne P Guh - daphne@sm.hivnet.ubc.ca; Wei Zhang - wzhang@cheos.ubc.ca; Nick Bansback - nbansback@cheos.ubc.ca; Zubin Amarsi - zamarsi@arthritisresearch.ca; C Laird Birmingham - clbirm@interchange.ubc.ca; Aslam H Anis* - aslam.anis@ubc.ca* Corresponding author    AbstractBackground: Overweight and obese persons are at risk of a number of medical conditions whichcan lead to further morbidity and mortality. The primary objective of this study is to provide anestimate of the incidence of each co-morbidity related to obesity and overweight using a meta-analysis.Methods: A literature search for the twenty co-morbidities identified in a preliminary search wasconducted in Medline and Embase (Jan 2007). Studies meeting the inclusion criteria (prospectivecohort studies of sufficient size reporting risk estimate based on the incidence of disease) wereextracted. Study-specific unadjusted relative risks (RRs) on the log scale comparing overweightwith normal and obese with normal were weighted by the inverse of their corresponding variancesto obtain a pooled RR with 95% confidence intervals (CI).Results: A total of 89 relevant studies were identified. The review found evidence for 18 co-morbidities which met the inclusion criteria. The meta-analysis determined statistically significantassociations for overweight with the incidence of type II diabetes, all cancers except esophageal(female), pancreatic and prostate cancer, all cardiovascular diseases (except congestive heartfailure), asthma, gallbladder disease, osteoarthritis and chronic back pain. We noted the strongestassociation between overweight defined by body mass index (BMI) and the incidence of type IIdiabetes in females (RR = 3.92 (95% CI: 3.10–4.97)). Statistically significant associations with obesitywere found with the incidence of type II diabetes, all cancers except esophageal and prostatecancer, all cardiovascular diseases, asthma, gallbladder disease, osteoarthritis and chronic back pain.Obesity defined by BMI was also most strongly associated with the incidence of type II diabetes infemales (12.41 (9.03–17.06)).Conclusion: Both overweight and obesity are associated with the incidence of multiple co-morbidities including type II diabetes, cancer and cardiovascular diseases. Maintenance of a healthyweight could be important in the prevention of the large disease burden in the future. FurtherPublished: 25 March 2009BMC Public Health 2009, 9:88 doi:10.1186/1471-2458-9-88Received: 3 July 2008Accepted: 25 March 2009This article is available from: http://www.biomedcentral.com/1471-2458/9/88© 2009 Guh et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Page 1 of 20(page number not for citation purposes)studies are needed to explore the biological mechanisms that link overweight and obesity withthese co-morbidities.BMC Public Health 2009, 9:88 http://www.biomedcentral.com/1471-2458/9/88BackgroundA substantial literature has emerged which has found thatoverweight and obesity are major causes of co-morbiditieswhich can lead to further morbidity and mortality [1-3].The related health care costs are substantial [4-6]. As thenumber of associated co-morbidities continues toincrease, systematic reviews and meta-analysis are impor-tant tools to summarize the findings and produce moreprecise estimates of risk associated with overweight andobesity.The primary objective of this study is to provide a compre-hensive review of the incidence of co-morbidities relatedto obesity and overweight. We have identified a numberof recent systematic reviews and meta-analyses on type IIdiabetes [7], cardiovascular diseases [8,9], cancer [10],breast cancer [11,12], esophageal or cardia adenocarci-noma [13], pancreatic cancer [14] and prostate cancer[15]. The rationale for re-conducting a review is threefold.Firstly, it has been reported that abdominal obesity,defined by waist circumference (WC) measurement incomparison to the more traditional obesity definition,based on Body Mass Index (BMI) measurement, is an evenbetter predictor of many cardiovascular diseases and typeII diabetes [16-24]. However, most recent reviews haveonly focused on obesity defined by BMI instead of WC.For example, a recent meta-analysis study has comparedBMI and WC as risk factors for ischaemic heart disease andstroke but it only included studies with population fromthe Asia Pacific region [8]. Also, only meta-analysis stud-ies on BMI and type II diabetes have been conducted [7].Secondly, associating the incidence of co-morbidities withoverweight and obesity can be done in many ways sincethere are many different definitions. For instance, manyprevious reviews have combined studies that have foundthe association with per unit change of BMI (kg/m2) andWC (cm) measurements [7-9,11,14,15]. We are interestedin measuring the incidence by categorization of over-weight and obesity defined by BMI and WC measure-ments, which has not been the focus of a majority ofprevious reviews.Thirdly, the previous meta-analysis studies primarilyfocused on individual co-morbidities and they were con-ducted by different authors and using different searchstrategies, inclusion criteria and analysis methods. Onlyone recent meta-analysis study conducted by Katzmarzykand Janssen comprehensively estimated the incidence ofeight different chronic diseases associated with obesity[5]. An objective of this review is to apply a consistentmethodology across all relevant co-morbidities. This ena-bles us to compare the number of studies and size of effectMethodsExposure variablesThe definition for overweight is having a BMI greater thanor equal to 25 kg/m2 and below 30 kg/m2. The definitionfor obesity is having a BMI greater than or equal to 30 kg/m2 [25,26]. According to the World Health Organization(WHO), the definition for abdominally overweight orobesity is a WC of greater than or equal to 80 cm and 88cm, respectively, for females, and 94 cm and 102 cm,respectively, for males [25,26].Disease outcomesPossible co-morbidities of overweight and obesity wereidentified from a preliminary search reviewed by an eatingdisorder and obesity expert and a review of previous sys-tematic reviews [1-3]. We also reviewed the leading causesof global burden of disease and included the diseasesreported with burden attributable to overweight and obes-ity [27]. Twenty co-morbidities were initially included inthis analysis: cancer (kidney, colorectal, prostate, ovarian,uterine/endometrial, esophageal, pancreatic, and post-menopausal breast), type II diabetes, cardiovascular dis-ease risk (hypertension, coronary artery disease, conges-tive heart failure, pulmonary embolism, stroke,dislipidaemia), gallbladder disease, chronic back pain,osteoarthritis, asthma, and sleep apnea.Literature reviewA literature search was conducted using the search terms:'Incidence, Prevalence, Risk, Risk Factors, Cohort Studies,Longitudinal Studies, Follow-up Studies, or ProspectiveStudies' in combination with 'Adipose Tissue, Obesity,Body Mass Index, or Body Composition' (all "exploded").These same search terms were applied to each co-morbid-ity (also "exploded") for both Medline and Embase searchengines to retrieve all potentially relevant English articles(until January, 2007). We also searched ISI Web of Sci-ence, Google Scholar, and the bibliographies of retrievedarticles.The articles obtained from the literature search were thenevaluated according to criteria set out in Figure 1. Criteriafor inclusion were: prospective cohort study of the generalpopulation of a Western country (countries in Europe orNorth America, Australia or New Zealand), relevant out-comes, a sample size of at least 200 subjects, and risk esti-mate based on the incidence of disease instead of themortality rate of disease. For large cohorts with multiplearticles meeting the defined criteria, the most recent articleor the article with the most usable information was used.Studies were excluded if they did not provide enough datato allow calculation of unadjusted relative risks (RRs)with 95% confidence intervals (CI) for the overweight andPage 2 of 20(page number not for citation purposes)across all co-morbidities. obese groups compared to the normal group. Dataextracted for study characteristics included study design,BMC Public Health 2009, 9:88 http://www.biomedcentral.com/1471-2458/9/88country, cohort name, duration of follow-up, number ofpatients in each study group, age range, gender and eth-nicity. Ascertainment of exposure and outcome variableswas also recorded. The literature search was conducted byZA, the decisions on inclusion and exclusion were madeby ZA, NB, DPG, CLB and the data were extracted by ZAand DPG.Meta-analysisRRs were measured by incidence rate ratios (IRRs) whenperson-time data were available and by the ratios of pro-portions (RR-Ps) when person-time data were not availa-ble. Study-specific unadjusted RRs on the log scalecomparing overweight with normal and obese with nor-mal were weighted by the inverse of their correspondingvariances to obtain a pooled RR with 95% CIs. We usedthe random-effects model to estimate the pooled RR usingthe maximum likelihood estimation method [28]. The Qstatistic was also calculated to assess the homogeneity ofRRs (log scale) [28]. Potential publication bias was visu-ally inspected by funnel plots and tested by asymmetrytests [29,30]; however it was performed only on thosemeta-analyses which included sufficient number of stud-ies (N>5). We also did various sensitivity analyses strati-fied on the length of follow-up, age criteria and country toexamine the robustness of the results.WC measurements were considered to be the better riskpredictor for some co-morbidities such as diabetes, hyper-the RRs based on WC measurements for these co-morbid-ities were available, they were pooled separately fromthose based on BMI and used as the final RRs for these co-morbidities. When both IRR and RR-P estimates wereavailable, both estimates were presented. Final results ofRRs were selected based on the number of pooled studies,the duration of study follow-up and the sample size ofincluded studiesResultsA total of 89 relevant and unique studies were identified;several studies featured for more than one co-morbidities.Of the 20 co-morbidities, 18 were identified to have atleast one study meeting the inclusion criteria. Some stud-ies were applicable to more than one co-morbidity. Nostudies were found for dislipidaemia and sleep apnea. Thetotal numbers of studies included for each co-morbidityvaried from 1 to 14. Reasons for exclusion are given inTable 1.The majority of the studies were conducted in US (55%)and in European countries (40%). Study characteristicssuch as age criteria, study follow-up, ascertainment ofexposure and outcome variables were reported by themajority of the studies. However, only a small number ofstudies reported sample ethnicity and of those, the major-ity was US studies. Among those US studies, one study(endometrial cancer) was about the black women [31]while for the remaining US studies, the proportion ofwhites ranged from 81% to 95%. The mean duration ofstudy follow-up was 12.5 (SD = 7.2) years. Over half ofthe studies (53%) were longer than 10 years while lessthan 10% of the studies were shorter than 5 years. BMIand WC measurements were clinically measured on 43%of the studies and were self-reported on 56% of the studieswhile one study did not provide such information.Regarding the ascertainment of cases, 43 (48%) studiesidentified cases from registry, database centre or clinicalevaluation; 34 (38%) studies were based on subject self-reported information with some kind of confirmationmethod such as medical records review; 6 studies werebased on medical records review and 5 studies (4 forasthma and 1 for type-2 diabetes) were relying on self-reported information alone. Note that cancer cases wereidentified from cancer registry/database on 66% of thestudies.Table 2 summarized our final results. Figures 2 to 18 pre-sented the detailed results including study-specific andpooled estimates. Results from the meta-analysis weresummarized in the following sections for each co-morbid-ity.Flowchart of article distribution for all diseasesigure 1Flowchart of article distribution for all diseases.Potentially relevant articles identified through Medline and Embase searches: n = A Articles excluded based on title and abstract review: n = B - Not prospective cohort: n = B (i) - Non-generalizable population: n = B (ii) - Irrelevant subject matter:  n = B (iii) - Drug or treatment: n = B (iv) - Food and nutrition: n = B (v) - Review article: n = B (vi) - Duplicate: n = B (vii)Articles ordered for more detailed review: n = C Articles excluded after detailed review: n = D - Population not generalizable: n = D (i) - Mortality rates used: n = D (ii) - Study too small: n = D (iii)  Articles meeting inclusion criteria and information extracted for meta-analysis: n = E Articles included in final meta-analysis calculations: n = G  Articles not amenable to meta-analysis: n = F - Required information not provided: n = F (i) - Same cohort already used: n = F (ii) Page 3 of 20(page number not for citation purposes)tension, coronary artery disease, congestive heart failure,stroke and gallbladder disease [16-24]. Therefore, whenBMC Public Health 2009, 9:88 http://www.biomedcentral.com/1471-2458/9/88Breast cancerIn total, 14 studies were identified for post menopausalbreast cancer (Figure 2) [19,32-44]. The pooled IRRs [95%CI] across categories of WC were 1.13 [1.01–1.07] foroverweight and 1.30 [1.17–1.44] for obesity while acrosscategories of BMI the IRRs were 1.08 [1.03–1.14] for over-weight and 1.13 [1.05–1.22] for obesity.Endometrial cancerIn total, 10 studies were identified to meet the inclusioncriteria for endometrial cancer (Figure 3)[19,31,35,36,42,45-49]. The study on the US blacksian population [31]. The pooled IRRs [95% CI] acrosscategories of WC were 1.15 [1.02–1.30] for overweightand 1.42 [0.80–2.49] for obesity while across categories ofBMI IRRs were 1.53 [1.45–1.61] for overweight and 3.22[2.91–3.56] for obesity.Ovarian cancerIn total, 9 studies were identified for ovarian cancer (Fig-ure 4) [19,35,36,42,45,50-53]. The single IRR [95% CI]across categories of WC were 0.61 [0.35–1.08] for over-weight and 1.35 [0.95–1.93] for obesity while pooledIRRs estimates across categories of BMI were 1.18 [1.12–Table 1: Article distribution for all diseases (see Figure 1 for explanation)Diseases A B B(i)B(ii)B(iii)B(iv)B(v)B(vi)B(vii)C D D(i)D(ii)D(iii)E F F(i)F(ii)GType II Diabetes 8142 8075 6687 18 1216 20 28 18 88 67 37 17 6 14 30 21 19 2 9Colorectal cancer 445 413 5 22 261 8 42 57 18 32 6 2 2 2 26 14 14 0 12Kidney cancer 2661 2606 55 12 2010 51 50 127 301 55 43 16 18 9 12 7 7 0 5Prostate cancer 491 462 28 1 258 0 37 52 86 29 14 5 9 0 15 7 6 1 8Breast cancer 2755 2682 145 18 1793 19 110 195 402 73 43 6 34 3 30 16 13 3 14Ovarian cancer 241 228 23 1 143 0 10 13 38 13 4 1 3 0 9 0 0 0 9Endometrial cancer 1249 1192 103 17 729 8 30 105 200 57 41 27 3 11 16 6 5 1 10Pancreatic cancer 155 131 5 0 81 0 14 7 24 24 15 5 10 0 9 3 2 1 6Esophageal cancer 230 222 23 0 103 2 13 34 47 8 6 4 2 0 2 1 1 0 1Hypertension 2882 2773 59 55 2256 53 78 81 191 109 88 23 53 12 21 17 17 0 4CAD 3041 2966 96 17 2202 42 66 82 461 75 50 10 27 13 25 14 11 3 11CHF 625 586 10 5 418 6 1 41 105 39 25 0 14 11 14 10 9 1 4PE 527 497 48 13 321 1 0 24 90 30 11 3 3 5 19 18 18 0 1Stroke 2783 2755 172 29 1747 17 24 234 532 28 17 6 5 6 11 4 4 0 7Asthma 1408 1359 89 13 598 47 47 84 481 49 36 2 25 9 13 9 9 0 4GD 319 305 29 9 175 0 7 32 53 14 5 0 2 3 9 5 5 0 4OA 853 824 43 10 390 51 38 123 169 29 14 5 2 7 15 12 12 0 3CBP 324 306 30 20 143 39 11 24 39 18 6 0 4 2 12 11 11 0 1CAD: Coronary Artery Disease; CHF: Congestive Heart Failure; PE: Pulmonary Embolism; GD: Gallbladder Disease; OA: Osteoarthritis; CBP: Chronic Back PainPage 4 of 20(page number not for citation purposes)women was not included in the final result as it showedsystematic difference from other studies mainly on Cauca-1.23] for overweight and 1.28 [1.20–1.36] for obesity.BMC Public Health 2009, 9:88 http://www.biomedcentral.com/1471-2458/9/88Page 5 of 20(page number not for citation purposes)Meta-analysis of studies for post menopausal breast cancerFigure 2Meta-analysis of studies for post menopausal breast cancer. *Q-statistic(p-value); F-up is follow-up in years; square shape: study- and gender- specific risk estimates; diamond shape: pooled risk estimates.McTiernan (2003)  [41]Barlow (2006) [43]Suzuki (2006) [39]Lukanova (2006)  [42]Sellers (2002) [32]Lukanova (2006)  [42]McTiernan (2003)  [41]Tehard (2004) [40]Suzuki (2006) [39]Chang (2006)  [38]Navarro Silvera (2006) [37]Jonsson (2003) [36]Tornberg (1994) [35]Dirx (2001)  [34]Sweeney (2004) [33]Sellers (2002) [32]Folsom (2000)  [19]Huang (1999)  [44]BMIBMIBMIBMIBMIBMIBMIBMIBMIBMIBMIBMIBMIBMIBMIWCWCWCFFFFFFFFFFFFFFFFFF50-7945-8455-7049+55-6949+50-7940-6555-7055-7440-5944-8355-7555-6956-8455-6955-6955+4.768.38.3138.34.79.78.39.316.42620.37.3161310.18USUSSwedenSwedenUSSwedenUSFranceSwedenUSCanadaSwedenSwedenNetherlandsUSUSUSUS741717291295182335362325493536274171414275182327541403181159847003625373665832573317025865RR-PRR-PRR-PRR-PRR-PIRRIRRIRRIRRIRRIRRIRRIRRIRRIRRRR-PIRRIRRStudy Obesity Sex Age F-up Country N OutcomeIRR & RR-P:IRR & RR-P:RR-P:RR-P:IRR:IRR:IRR & RR-P:RR-P:IRR:IRR & RR-P:RR-P:IRR:IRR & RR-P:RR-P:IRR:RR-P:IRR:Europe studies (6)US/Canada studies (6)Europe studies (2)US studies (3)Europe studies (6)US/Canada studies (4)min.age>=55 (6)min.age>=55 (2)min.age>=55 (5)F-up>=5 yrs (11)F-up>=5 yrs (4)F-up>=5 yrs (9)All studies (12)All studies (5)All studies (10)All studies (1)All studies (2)5.2(0.63)*20.5(0)*0.4(0.54)*13(0)*4.6(0.47)*7.3(0.06)*6.7(0.35)*2.9(0.09)*3.1(0.54)*15.6(0.21)*7.9(0.05)*7.7(0.47)*25.8(0.03)*13.8(0.01)*12(0.22)*1.6(0.21)*OverweightRRRisk Est (95% CI)0.96  (0.86  - 1.07 )1.06  (0.99  - 1.13 )1.10  (0.98  - 1.24 )1.19  (0.96  - 1.47 )1.27  (1.14  - 1.41 )0.92  (0.74  - 1.13 )0.97  (0.87  - 1.09 )1.06  (0.92  - 1.20 )1.06  (0.94  - 1.19 )1.09  (0.93  - 1.28 )1.09  (0.98  - 1.22 )1.10  (1.00  - 1.40 )1.13  (0.98  - 1.30 )1.18  (1.03  - 1.35 )1.20  (1.09  - 1.33 )1.16  (1.02  - 1.32 )1.05  (0.90  - 1.23 )1.22  (1.04  - 1.42 )1.09  (1.02  - 1.15 )1.10  (1.02  - 1.19 )1.12  (1.01  - 1.24 )1.09  (0.95  - 1.24 )1.09  (1.02  - 1.15 )1.08  (0.99  - 1.18 )1.15  (1.08  - 1.23 )1.18  (1.06  - 1.32 )1.13  (1.07  - 1.21 )1.11  (1.06  - 1.17 )1.15  (1.05  - 1.25 )1.10  (1.05  - 1.16 )1.10  (1.04  - 1.15 )1.11  (1.01  - 1.22 )1.08  (1.03  - 1.14 )1.16  (1.02  - 1.32 )1.13  (1.01  - 1.27 )0.5 1 2 4 160.5 1 2 4 16ObeseRRRisk Est (95% CI)0.98  (0.88  - 1.10 )1.09  (1.01  - 1.18 )1.17  (0.99  - 1.39 )1.40  (1.07  - 1.83 )1.38  (1.22  - 1.57 )1.06  (0.81  - 1.39 )1.02  (0.91  - 1.14 )1.38  (1.10  - 1.75 )1.15  (0.96  - 1.37 )0.99  (0.82  - 1.19 )1.04  (0.88  - 1.22 )1.20  (0.80  - 1.60 )1.21  (1.04  - 1.42 )1.07  (0.85  - 1.35 )1.30  (1.17  - 1.43 )1.34  (1.20  - 1.49 )1.31  (1.16  - 1.48 )1.26  (1.05  - 1.52 )1.30  (1.02  - 1.65 )1.14  (1.03  - 1.26 )1.23  (1.06  - 1.42 )1.14  (0.97  - 1.34 )1.30  (1.02  - 1.65 )1.10  (0.98  - 1.23 )1.20  (1.10  - 1.31 )1.28  (1.12  - 1.47 )1.17  (1.07  - 1.28 )1.17  (1.09  - 1.25 )1.23  (1.09  - 1.37 )1.15  (1.07  - 1.24 )1.15  (1.07  - 1.23 )1.17  (1.04  - 1.32 )1.13  (1.05  - 1.22 )1.34  (1.20  - 1.49 )1.30  (1.17  - 1.44 )0.5 1 2 4 16 320.5 1 2 4 16 32Meta-analysis of studies for endometrial cancerFigure 3Meta-analysis of studies for endometrial cancer. *Q-statistic(p-value); **pre-menopause, square shape: study- and gen-der- specific risk estimates; diamond shape: pooled risk estimates.Tornberg (1994) [35]Lukanova (2006) [42]Rapp (2005) [45]Folsom (2003) [49]Wise (2005) [31]Jonsson (2003) [36]Lukanova (2006) [42]Silvera (2005) [48]Bjorge (2006) [47]Schouten (2004) [46]Tornberg (1994) [35]Rapp (2005) [45]Folsom (2000) [19]Wise (2005) [31]BMIBMIBMIBMIBMIBMIBMIBMIBMIBMIBMIBMIWCWCFFFFFFFFFFFFFF25-7530-6135-5455-6921-Pre-M**44-8330-6140-5920-7455-6925-7535-5455-6921-Pre-M**20.38.310.213.14268.316.424.39.320.310.274SwedenSwedenAustriaUSUSSwedenSwedenCanadaNorwayNetherlandsSwedenAustriaUSUS47003353627848423335215061159835362343911036877173947003784843170217876RR-PRR-PRR-PIRRIRRIRRIRRIRRIRRIRRIRRIRRIRRIRRStudy Obesity Sex Age F-up Country N OutcomeIRR:IRR:IRR:IRR:RR-P:IRR:IRR:exclude black cohort (8)Europe studies (6)US/Canada studies (3)min.age>=55 (2)All studies (3)All studies (9)All studies (2)14.4(0.05)*6.3(0.28)*5.2(0.07)*3.7(0.05)*2.1(0.35)*41.5(0)*0(0.98)*OverweightRRRisk Est (95% CI)1.68  (1.33  - 2.14 )1.76  (1.15  - 2.71 )2.30  (1.61  - 3.28 )1.09  (0.84  - 1.41 )1.17  (1.05  - 1.29 )1.30  (0.90  - 1.90 )1.34  (0.87  - 2.07 )1.53  (1.22  - 1.92 )1.58  (1.50  - 1.65 )1.60  (1.19  - 2.14 )1.77  (1.40  - 2.25 )2.26  (1.58  - 3.22 )1.14  (0.79  - 1.65 )1.15  (1.01  - 1.31 )1.53  (1.45  - 1.61 )1.59  (1.52  - 1.66 )1.27  (1.13  - 1.42 )1.30  (1.00  - 1.69 )1.90  (1.53  - 2.36 )1.55  (1.42  - 1.69 )1.15  (1.02  - 1.30 )0.5 1 2 4 160.5 1 2 4 16ObeseRRRisk Est (95% CI)2.61  (2.04  - 3.34 )3.59  (2.29  - 5.62 )4.58  (3.18  - 6.60 )3.41  (2.69  - 4.31 )1.06  (0.96  - 1.18 )3.20  (2.00  - 5.20 )2.90  (1.85  - 4.54 )3.73  (2.94  - 4.72 )2.91  (2.76  - 3.06 )3.30  (2.32  - 4.69 )2.92  (2.28  - 3.74 )4.82  (3.35  - 6.95 )2.17  (1.67  - 2.82 )0.96  (0.85  - 1.08 )3.22  (2.91  - 3.56 )2.95  (2.80  - 3.10 )2.36  (1.22  - 4.54 )3.37  (2.77  - 4.10 )3.39  (2.51  - 4.58 )2.86  (2.17  - 3.78 )1.42  (0.80  - 2.49 )0.5 1 2 4 16 320.5 1 2 4 16 32BMC Public Health 2009, 9:88 http://www.biomedcentral.com/1471-2458/9/88Page 6 of 20(page number not for citation purposes)Meta-analysis of studies for ovarian cancerFigure 4Meta-analysis of studies for ovarian cancer. *Q-statistic(p-value); F-up is follow-up in years; square shape: study- and gen-der- specific risk estimates; diamond shape: pooled risk estimates.Tornberg (1994) [35]Engeland (2003) [50]Fairfield (2002) [53]Rapp (2005) [45]Lukanova (2006) [42]Fairfield (2002) [53]Tornberg (1994) [35]Jonsson (2003) [36]Schouten (2003) [52]Anderson (2004) [51]Engeland (2003) [50]Lukanova (2006) [42]Rapp (2005) [45]Folsom (2000) [19]BMIBMIBMIBMIBMIBMIBMIBMIBMIBMIBMIBMIBMIWCFFFFFFFFFFFFFF25-7520-7430-5535-5430-6030-5525-7544-8355-6955-6920-7430-6035-5455-6920.32315.610.28.315.620.3267.315238.310.28.5SwedenNorwayUSAustriaSwedenUSSwedenSwedenNetherlandsUSNorwaySwedenAustriaUS47003102446816367848435362163647003115981636313811024468353627848431702RR-PRR-PRR-PRR-PRR-PIRRIRRIRRIRRIRRIRRIRRIRRIRRStudy Obesity Sex Age F-up Country N OutcomeIRR:IRR:IRR:IRR:RR-P:IRR:IRR:Europe studies (6)US studies (2)min.age>=55 (2)min.age<55 (6)All studies (5)All studies (8)All studies (1)6.3(0.27)*0.9(0.34)*0(0.89)*9.9(0.08)*11.3(0.02)*10.2(0.18)*OverweightRRRisk Est (95% CI)0.91  (0.71  - 1.16 )1.14  (1.09  - 1.20 )1.37  (1.08  - 1.73 )1.57  (1.05  - 2.35 )1.76  (1.11  - 2.78 )0.94  (0.74  - 1.19 )0.96  (0.75  - 1.23 )1.00  (0.70  - 1.50 )1.09  (0.79  - 1.51 )1.13  (0.83  - 1.53 )1.20  (1.14  - 1.26 )1.46  (0.92  - 2.31 )1.54  (1.03  - 2.30 )0.61  (0.35  - 1.08 )1.19  (1.13  - 1.25 )1.01  (0.84  - 1.21 )1.11  (0.89  - 1.39 )1.18  (1.13  - 1.24 )1.29  (1.12  - 1.50 )1.18  (1.12  - 1.23 )0.61  (0.35  - 1.08 )0.1 0.5 1 2 4 160.1 0.5 1 2 4 16ObeseRRRisk Est (95% CI)1.15  (0.87  - 1.52 )1.14  (1.07  - 1.22 )1.92  (1.43  - 2.57 )1.88  (1.14  - 3.08 )1.98  (1.12  - 3.51 )1.08  (0.80  - 1.45 )1.29  (0.98  - 1.70 )0.30  (0.10  - 1.10 )1.44  (0.89  - 2.32 )1.17  (0.83  - 1.65 )1.28  (1.20  - 1.37 )1.73  (0.97  - 3.07 )1.97  (1.20  - 3.24 )1.35  (0.95  - 1.93 )1.29  (1.21  - 1.38 )1.12  (0.89  - 1.40 )1.26  (0.95  - 1.66 )1.28  (1.20  - 1.36 )1.47  (1.13  - 1.91 )1.28  (1.20  - 1.36 )1.35  (0.95  - 1.93 )0.1 0.5 1 2 4 16 320.1 0.5 1 2 4 16 32Meta-analysis of studies for colorectal cancer-femalesFigure 5Meta-analysis of studies for colorectal cancer-females. *Q-statistic(p-value); F-up is follow-up in years; square shape: study- and gender- specific risk estimates; diamond shape: pooled risk estimates.Pischon (2006) [57]Lin (2004) [61]Moore (2004) [56]Lukanova (2005) [42]Rapp (2005) [45]McCarl (2006) [62]Lukanova (2005) [42]Lin (2004) [61]Martinez (1997) [60]Engeland (2005) [59]Moore (2004) [56]Ford (1999) [58]Rapp (2005) [45]Moore (2004) [56]Pischon (2006) [57]Folsom (2000) [19]Moore (2004) [56]BMIBMIBMIBMIBMIBMIBMIBMIBMIBMIBMIBMIBMIWCWCWCWCFFFFFFFFFFFFFFFFF25-7045+30-7930-6135-5455-6930-6145+30-5520-7430-7925-7435-5430-7925-7055-6930-796.37.430.48.310.2158.37.45.723.730.416.610.230.46.310.230.4EuropeanUSUSSwedenAustriaUSSwedenUSUSNorwayUSUSAustriaUSEuropeanUSUS238546376714221353627848435197353623767189488103707742217914784844221238546317024221RR-PRR-PRR-PRR-PRR-PIRRIRRIRRIRRIRRIRRIRRIRRRR-PRR-PIRRIRRStudy Obesity Sex Age F-up Country N OutcomeIRR & RR-P:IRR & RR-P:RR-P:RR-P:IRR:IRR:IRR & RR-P:IRR & RR-P:RR-P:RR-P:IRR:IRR:RR-P:RR-P:IRR:IRR:RR-P:IRR:RR-P:IRR:Europe studies (4)US studies (5)Europe studies (3)US studies (2)Europe studies (3)US studies (5)max.age>=65 (6)max.age<65 (3)max.age>=65 (3)max.age<65 (2)max.age>=65 (5)max.age<65 (3)F-up>=10 yrs (1)F-up<10 yrs (4)F-up>=10 yrs (4)F-up<10 yrs (4)All studies (5)All studies (8)All studies (2)All studies (2)15.7(0.01)*5(0.55)*10.2(0.01)*0.3(0.57)*5.5(0.06)*4.4(0.36)*15.9(0.03)*9.6(0.05)*0.7(0.71)*0.6(0.43)*11.1(0.03)*6.9(0.03)*10.9(0.01)*10.3(0.02)*8.1(0.05)*10.9(0.03)*18.3(0.01)*0(0.85)*0(0.89)*OverweightRRRisk Est (95% CI)1.29  (1.09  - 1.52 )1.32  (0.97  - 1.80 )1.50  (1.09  - 2.08 )1.64  (1.06  - 2.53 )1.99  (1.61  - 2.46 )1.22  (1.05  - 1.41 )1.28  (0.83  - 1.97 )1.32  (0.96  - 1.80 )1.32  (1.04  - 1.68 )1.54  (1.50  - 1.58 )1.60  (1.15  - 2.23 )1.78  (1.16  - 2.74 )1.95  (1.58  - 2.42 )1.37  (0.76  - 2.47 )1.45  (1.23  - 1.72 )1.24  (0.95  - 1.61 )1.30  (0.72  - 2.36 )1.49  (1.32  - 1.68 )1.31  (1.18  - 1.46 )1.66  (1.29  - 2.13 )1.40  (1.12  - 1.76 )1.55  (1.50  - 1.59 )1.31  (1.18  - 1.46 )1.39  (1.27  - 1.52 )1.55  (1.22  - 1.96 )1.33  (1.16  - 1.52 )1.92  (1.58  - 2.32 )1.42  (1.27  - 1.58 )1.55  (1.22  - 1.96 )1.50  (1.09  - 2.08 )1.58  (1.27  - 1.95 )1.44  (1.27  - 1.63 )1.49  (1.22  - 1.83 )1.55  (1.30  - 1.86 )1.45  (1.30  - 1.62 )1.45  (1.23  - 1.70 )1.25  (0.98  - 1.59 )0.5 1 2 4 160.5 1 2 4 16ObeseRRRisk Est (95% CI)1.21  (1.02  - 1.43 )1.33  (0.93  - 1.92 )1.29  (0.83  - 2.01 )2.60  (1.60  - 4.23 )1.72  (1.29  - 2.30 )1.44  (1.22  - 1.70 )1.93  (1.19  - 3.14 )1.34  (0.93  - 1.93 )1.52  (1.16  - 1.97 )1.74  (1.68  - 1.81 )1.56  (1.00  - 2.45 )1.66  (1.06  - 2.61 )1.81  (1.35  - 2.42 )1.74  (0.98  - 3.08 )1.54  (1.31  - 1.81 )1.52  (1.23  - 1.87 )1.82  (1.02  - 3.25 )1.64  (1.34  - 2.00 )1.47  (1.30  - 1.66 )1.61  (1.20  - 2.16 )1.32  (0.99  - 1.75 )1.74  (1.68  - 1.81 )1.47  (1.30  - 1.66 )1.50  (1.32  - 1.70 )1.68  (1.38  - 2.03 )1.24  (1.07  - 1.43 )1.92  (1.50  - 2.46 )1.61  (1.45  - 1.78 )1.68  (1.38  - 2.03 )1.29  (0.83  - 2.01 )1.53  (1.20  - 1.94 )1.64  (1.47  - 1.83 )1.60  (1.34  - 1.91 )1.49  (1.21  - 1.82 )1.66  (1.52  - 1.81 )1.55  (1.33  - 1.82 )1.55  (1.27  - 1.88 )0.5 1 2 4 16 320.5 1 2 4 16 32BMC Public Health 2009, 9:88 http://www.biomedcentral.com/1471-2458/9/88Page 7 of 20(page number not for citation purposes)Meta-analysis of studies for colorectal cancer-malesFigure 6Meta-analysis of studies for colorectal cancer-males. *Q-statistic(p-value); F-up is follow-up in years; square shape: study- and gender- specific risk estimates; diamond shape: pooled risk estimates.Pischon (2006) [57]Lukanova (2005) [42]Moore (2004) [56]Giovannucci (1995) [55]Rapp (2005) [45]Lukanova (2005) [42]Engeland (2005) [59]MacInnis (2004) [54]Ford (1999) [58]Giovannucci (1995) [55]Moore (2004) [56]Rapp (2005) [45]Pischon (2006) [57]Moore (2004) [56]Moore (2004) [56]Giovannucci (1995) [55]MacInnis (2004) [54]BMIBMIBMIBMIBMIBMIBMIBMIBMIBMIBMIBMIWCWCWCWCWCMMMMMMMMMMMMMMMMM25-7030-6130-7940-7535-5430-6120-7440-6925-7440-7530-7935-5425-7030-7930-7940-7540-696.38.230.45.59.68.223.78.816.65.530.49.66.330.430.45.58.8EuropeanSwedenUSUSAustriaSwedenNorwayAustraliaUSUSUSAustriaEuropeanUSUSUSAustralia12973133424334547723674473342496290116556550647723334567447129731334533453105516556RR-PRR-PRR-PRR-PRR-PIRRIRRIRRIRRIRRIRRIRRRR-PRR-PIRRIRRIRRStudy Obesity Sex Age F-up Country N OutcomeIRR & RR-P:IRR & RR-P:RR-P:RR-P:IRR:IRR:IRR & RR-P:IRR & RR-P:RR-P:RR-P:IRR:IRR:RR-P:RR-P:IRR:IRR:RR-P:IRR:IRR & RR-P:IRR & RR-P:IRR:IRR & RR-P:IRR:IRR:Europe studies (4)US studies (3)Europe studies (3)US studies (2)Europe studies (3)US studies (3)max.age>=65 (6)max.age<65 (2)max.age>=65 (3)max.age<65 (2)max.age>=65 (5)max.age<65 (2)F-up>=10 yrs (1)F-up<10 yrs (4)F-up>=10 yrs (3)F-up<10 yrs (4)All studies (5)All studies (7)Europe studies (1)US studies (2)US studies (2)F-up<10 yrs (3)F-up<10 yrs (2)All studies (3)20.9(0)*0.2(1)*12.9(0)*0(0.84)*7.9(0.02)*0.1(0.95)*7.8(0.35)*6.6(0.09)*4.5(0.11)*1.6(0.21)*1.2(0.88)*4.8(0.03)*13.6(0)*0.5(0.77)*5.2(0.16)*13.7(0.01)*9.1(0.17)*0.2(0.9)*0(0.86)*4.4(0.11)*0.3(0.59)*0.7(0.7)*OverweightRRRisk Est (95% CI)1.14  (0.97  - 1.35 )1.43  (0.99  - 2.09 )1.51  (1.03  - 2.22 )1.59  (1.18  - 2.16 )1.90  (1.52  - 2.36 )1.16  (0.80  - 1.69 )1.40  (1.37  - 1.44 )1.43  (0.92  - 2.23 )1.48  (0.98  - 2.24 )1.60  (1.18  - 2.16 )1.61  (1.09  - 2.38 )1.89  (1.52  - 2.36 )1.37  (1.14  - 1.65 )1.58  (1.09  - 2.28 )1.71  (1.17  - 2.50 )1.81  (1.07  - 3.06 )2.17  (1.43  - 3.30 )1.44  (1.20  - 1.74 )1.57  (1.27  - 1.93 )1.45  (1.11  - 1.90 )1.56  (1.23  - 1.98 )1.53  (1.29  - 1.81 )1.57  (1.27  - 1.93 )1.40  (1.36  - 1.44 )1.52  (1.06  - 2.18 )1.36  (1.10  - 1.67 )1.76  (1.46  - 2.13 )1.41  (1.37  - 1.44 )1.52  (1.06  - 2.18 )1.51  (1.03  - 2.22 )1.48  (1.19  - 1.83 )1.41  (1.37  - 1.44 )1.54  (1.25  - 1.89 )1.48  (1.23  - 1.79 )1.51  (1.37  - 1.67 )1.37  (1.14  - 1.65 )1.74  (1.28  - 2.37 )1.74  (1.28  - 2.37 )1.73  (1.33  - 2.26 )2.02  (1.46  - 2.80 )1.88  (1.47  - 2.41 )0.5 1 2 4 160.5 1 2 4 16ObeseRRRisk Est (95% CI)1.38  (1.14  - 1.67 )1.91  (1.15  - 3.18 )2.04  (1.25  - 3.33 )1.87  (1.24  - 2.82 )2.84  (2.13  - 3.80 )1.65  (0.99  - 2.75 )1.67  (1.59  - 1.76 )1.90  (1.18  - 3.04 )1.28  (0.71  - 2.33 )1.88  (1.24  - 2.84 )2.38  (1.44  - 3.93 )3.08  (2.31  - 4.12 )1.72  (1.45  - 2.05 )2.11  (1.39  - 3.20 )2.45  (1.59  - 3.76 )3.38  (2.20  - 5.19 )3.03  (2.05  - 4.48 )1.77  (1.30  - 2.40 )1.86  (1.40  - 2.46 )1.94  (1.33  - 2.83 )1.94  (1.41  - 2.65 )2.00  (1.40  - 2.87 )1.86  (1.40  - 2.46 )1.66  (1.58  - 1.74 )2.34  (1.47  - 3.72 )1.65  (1.30  - 2.09 )2.58  (2.01  - 3.32 )1.68  (1.60  - 1.77 )2.34  (1.47  - 3.72 )2.04  (1.25  - 3.33 )1.93  (1.44  - 2.60 )1.68  (1.59  - 1.77 )2.13  (1.59  - 2.86 )1.95  (1.51  - 2.51 )1.95  (1.59  - 2.39 )1.72  (1.45  - 2.05 )2.87  (2.12  - 3.89 )2.87  (2.12  - 3.89 )2.49  (1.74  - 3.57 )3.18  (2.38  - 4.25 )2.93  (2.31  - 3.73 )0.5 1 2 4 16 320.5 1 2 4 16 32Meta-analysis of studies for kidney cancerFigure 7Meta-analysis of studies for kidney cancer. *Q-statistic(p-value); F-up is follow-up in years; square shape: study- and gen-der- specific risk estimates; diamond shape: pooled risk estimates.Lukanova (2006) [42]Pischon (2006) [57]Rapp (2005) [45]Lukanova (2006) [42]Flaherty (2005) [64]Bjorge (2004) [65]Rapp (2005) [45]Pischon (2006) [57]Lukanova (2006) [42]Rapp (2005) [45]Lukanova (2006) [42]Bjorge (2004) [65]Flaherty (2005) [64]Rapp (2005) [45]BMIBMIBMIBMIBMIBMIBMIBMIBMIBMIBMIBMIBMIBMIFFFFFFFMMMMMMM30-6025-7035-5430-6020-7435-5425-7030-6035-5430-6020-7435-548.3610.28.3NA2310.268.29.68.223NA9.6SwedenEuropeanAustriaSwedenUSNorwayAustriaEuropeanSwedenAustriaSwedenNorwayUSAustria3536221880578484353621181911037788784841297453342467447334249634424895367447RR-PRR-PRR-PIRRIRRIRRIRRRR-PRR-PRR-PIRRIRRIRRIRRStudy Obesity Sex Age F-up Country N OutcomeIRR & RR-P:IRR:RR-P:IRR:IRR & RR-P:IRR:RR-P:IRR:Europe studies (4)Europe studies (3)All studies (3)All studies (4)Europe studies (4)Europe studies (3)All studies (3)All studies (4)16.4(0.01)*8.9(0.01)*5(0.08)*9.1(0.03)*14.7(0.01)*3(0.23)*11(0)*3(0.39)*OverweightRRRisk Est (95% CI)1.20  (0.43  - 3.38 )1.91  (1.27  - 2.89 )3.38  (2.14  - 5.32 )0.83  (0.30  - 2.34 )1.70  (1.17  - 2.47 )1.80  (1.65  - 1.96 )3.31  (2.10  - 5.23 )0.80  (0.55  - 1.15 )1.47  (0.57  - 3.79 )1.92  (1.32  - 2.78 )1.14  (0.44  - 2.95 )1.39  (1.30  - 1.48 )1.41  (0.94  - 2.10 )1.92  (1.32  - 2.78 )1.83  (1.69  - 1.99 )1.83  (1.68  - 1.99 )2.29  (1.55  - 3.37 )1.82  (1.68  - 1.98 )1.35  (0.97  - 1.87 )1.40  (1.31  - 1.49 )1.34  (0.80  - 2.25 )1.40  (1.31  - 1.49 )0.1 0.5 1 2 4 160.1 0.5 1 2 4 16ObeseRRRisk Est (95% CI)2.39  (0.80  - 7.14 )1.91  (1.27  - 2.89 )2.04  (1.05  - 3.96 )1.83  (0.61  - 5.47 )2.70  (1.74  - 4.18 )2.65  (2.40  - 2.94 )2.15  (1.11  - 4.17 )1.25  (0.84  - 1.86 )3.91  (1.37  - 11.14)2.43  (1.45  - 4.07 )3.29  (1.15  - 9.37 )1.77  (1.56  - 2.02 )1.44  (0.72  - 2.87 )2.64  (1.57  - 4.42 )2.59  (2.35  - 2.85 )2.63  (2.38  - 2.91 )1.99  (1.42  - 2.78 )2.64  (2.39  - 2.90 )1.76  (1.32  - 2.35 )1.83  (1.62  - 2.07 )1.97  (1.20  - 3.22 )1.82  (1.61  - 2.05 )0.1 0.5 1 2 4 16 320.1 0.5 1 2 4 16 32BMC Public Health 2009, 9:88 http://www.biomedcentral.com/1471-2458/9/88Page 8 of 20(page number not for citation purposes)Meta-analysis of studies for pancreatic cancerFigure 8Meta-analysis of studies for pancreatic cancer. *Q-statistic(p-value); F-up is follow-up in years; square shape: study- and gender- specific risk estimates; diamond shape: pooled risk estimates.Sinner (2005) [69]Patel (2005) [68]Lukanova (2006) [42]Rapp (2005) [45]Sinner (2005) [69]Patel (2005) [68]Lukanova (2006) [42]Larsson (2005)[67]Michaud (2001)[66]Rapp (2005) [45]Patel (2005) [68]Rapp (2005) [45]Patel (2005) [68]Larsson (2005)[67]Michaud (2001)[66]Rapp (2005) [45]BMIBMIBMIBMIBMIBMIBMIBMIBMIBMIBMIBMIBMIBMIBMIBMIFFFFFFFFFFMMMMMM55-6950-7430-6035-5455-6950-7430-6045-8330-5535-5450-7435-5450-7445-8340-7535-541278.310.21278.36.819.410.279.676.8129.6USUSSwedenAustriaUSUSSwedenSwedenUSAustriaUSAustriaUSSwedenUSAustria380027603835362784843800276038353623714711704178484695896744769589459064664867447RR-PRR-PRR-PRR-PIRRIRRIRRIRRIRRIRRRR-PRR-PIRRIRRIRRIRRStudy Obesity Sex Age F-up Country N OutcomeRR-P:RR-P:IRR:IRR:RR-P:RR-P:IRR:IRR:IRR:IRR:RR-P:IRR:IRR:IRR:IRR:IRR:RR-P:IRR:Europe studies (2)US studies (2)Europe studies (3)US studies (3)min.age>=45 (2)min.age<45 (2)min.age>=45 (3)min.age<45 (3)F-up>=10 yrs (2)F-up<10 yrs (4)All studies (4)All studies (6)Europe studies (2)US studies (2)F-up>=10 yrs (1)F-up<10 yrs (3)All studies (2)All studies (4)0(0.93)*0.3(0.59)*0.6(0.73)*4.4(0.11)*0.3(0.59)*0(0.93)*2(0.37)*0.6(0.73)*4.4(0.04)*2(0.58)*5.7(0.13)*6.9(0.23)*3.1(0.08)*2.9(0.09)*5.4(0.07)*5(0.03)*6.6(0.09)*OverweightRRRisk Est (95% CI)0.92  (0.67  - 1.26 )1.07  (0.69  - 1.65 )1.71  (0.88  - 3.31 )1.78  (1.01  - 3.12 )0.91  (0.66  - 1.24 )1.07  (0.69  - 1.66 )1.23  (0.63  - 2.39 )1.44  (0.82  - 2.54 )1.46  (1.06  - 2.01 )1.75  (1.00  - 3.06 )0.93  (0.63  - 1.38 )2.06  (1.16  - 3.64 )0.92  (0.62  - 1.36 )1.02  (0.60  - 1.73 )1.46  (1.02  - 2.09 )2.05  (1.16  - 3.64 )1.75  (1.14  - 2.68 )0.97  (0.75  - 1.25 )1.47  (1.03  - 2.11 )1.13  (0.85  - 1.50 )0.97  (0.75  - 1.25 )1.75  (1.14  - 2.68 )1.03  (0.81  - 1.30 )1.48  (1.14  - 1.91 )1.15  (0.79  - 1.67 )1.31  (1.00  - 1.72 )1.24  (0.90  - 1.69 )1.24  (0.98  - 1.56 )1.43  (0.83  - 2.48 )1.18  (0.85  - 1.62 )1.46  (1.02  - 2.09 )1.21  (0.79  - 1.85 )1.33  (0.75  - 2.37 )1.28  (0.94  - 1.75 )0.5 1 2 4 160.5 1 2 4 16ObeseRRRisk Est (95% CI)1.06  (0.75  - 1.50 )1.49  (0.90  - 2.46 )1.44  (0.57  - 3.62 )2.82  (1.51  - 5.25 )1.07  (0.76  - 1.50 )1.50  (0.91  - 2.47 )1.00  (0.40  - 2.52 )1.32  (0.56  - 3.08 )2.10  (1.42  - 3.11 )2.97  (1.59  - 5.53 )2.06  (1.33  - 3.20 )3.92  (1.97  - 7.82 )2.04  (1.32  - 3.18 )1.99  (1.00  - 3.98 )1.78  (1.01  - 3.11 )4.25  (2.13  - 8.48 )2.28  (1.36  - 3.82 )1.18  (0.89  - 1.57 )1.73  (0.97  - 3.09 )1.48  (1.03  - 2.13 )1.18  (0.89  - 1.57 )2.28  (1.36  - 3.82 )1.20  (0.92  - 1.57 )2.11  (1.54  - 2.88 )1.48  (0.90  - 2.44 )1.68  (1.16  - 2.44 )1.57  (1.06  - 2.33 )1.60  (1.17  - 2.20 )2.91  (1.53  - 5.54 )1.94  (1.37  - 2.74 )1.78  (1.01  - 3.11 )2.55  (1.62  - 3.99 )2.74  (1.60  - 4.67 )2.29  (1.65  - 3.19 )0.5 1 2 4 16 320.5 1 2 4 16 32Meta-analysis of studies for prostate cancerFigure 9Meta-analysis of studies for prostate cancer. *Q-statistic(p-value); F-up is follow-up in years; square shape: study- and gender- specific risk estimates; diamond shape: pooled risk estimates.Lund Nilsen (1999) [71]Lukanova (2006) [42]Habel (2000) [74]Rapp (2005) [45]Giovannucci (1997) [73]Lukanova (2006) [42]Jonsson (2003) [36]Zeegers (2005) [72]Lund Nilsen (1999) [71]Engeland (2003) [70]Rapp (2005) [45]BMIBMIBMIBMIBMIBMIBMIBMIBMIBMIBMIMMMMMMMMMMM40+30-6018-8435-5440-7530-6044-8355-6940+20-7435-5410.48.219.59.67.28.2229.310.4219.6NorwaySwedenUSAustriaUSSwedenSwedenNetherlandsNorwayNorwayAustria2411334247071267447466943342489982335241195145967447RR-PRR-PRR-PRR-PIRRIRRIRRIRRIRRIRRIRRStudy Obesity Sex Age F-up Country N OutcomeRR-P:IRR:IRR:IRR:RR-P:RR-P:IRR:IRR:RR-P:IRR:Europe studies (3)Europe studies (6)min.age>=40 (4)min.age<40 (3)F-up>=10 yrs (2)F-up<10 yrs (2)F-up>=10 yrs (3)F-up<10 yrs (4)All studies (4)All studies (7)15.7(0)*61.7(0)*2.2(0.52)*20.7(0)*2.6(0.11)*5.9(0.02)*16.9(0)*49.1(0)*16.6(0)*102.4(0)*OverweightRRRisk Est (95% CI)1.10  (0.92  - 1.31 )1.24  (1.03  - 1.51 )1.30  (1.17  - 1.45 )1.65  (1.46  - 1.86 )0.95  (0.85  - 1.06 )0.97  (0.80  - 1.17 )1.00  (0.80  - 1.20 )1.05  (0.94  - 1.17 )1.08  (0.91  - 1.29 )1.40  (1.37  - 1.43 )1.65  (1.45  - 1.86 )1.32  (1.08  - 1.62 )1.17  (1.01  - 1.36 )1.02  (0.94  - 1.11 )1.28  (1.01  - 1.61 )1.24  (1.12  - 1.37 )1.45  (1.19  - 1.78 )1.18  (0.99  - 1.40 )1.12  (0.90  - 1.41 )1.32  (1.14  - 1.53 )1.14  (1.00  - 1.31 )0.5 1 2 4 160.5 1 2 4 16ObeseRRRisk Est (95% CI)1.20  (0.98  - 1.48 )0.96  (0.69  - 1.33 )1.15  (1.02  - 1.31 )1.30  (1.06  - 1.60 )0.76  (0.62  - 0.91 )0.77  (0.56  - 1.07 )1.00  (0.60  - 1.50 )0.82  (0.60  - 1.13 )1.22  (0.99  - 1.50 )1.46  (1.40  - 1.54 )1.41  (1.14  - 1.74 )1.19  (1.03  - 1.38 )1.14  (0.93  - 1.39 )0.93  (0.75  - 1.16 )1.27  (0.92  - 1.75 )1.17  (1.05  - 1.30 )1.14  (0.88  - 1.47 )1.27  (1.10  - 1.47 )0.91  (0.69  - 1.20 )1.17  (1.06  - 1.30 )1.05  (0.85  - 1.30 )0.5 1 2 4 16 320.5 1 2 4 16 32BMC Public Health 2009, 9:88 http://www.biomedcentral.com/1471-2458/9/88Page 9 of 20(page number not for citation purposes)Meta-analysis of studies for type II diabetesFigure 10Meta-analysis of studies for type II diabetes. *Q-statistic(p-value); F-up is follow-up in years; square shape: study- and gender- specific risk estimates; diamond shape: pooled risk estimates.Meisinger (2006) [77]Weinstein (2004) [76]Meisinger (2006) [77]Folsom (2000) [19]Weinstein (2004) [76]Hu (2001) [75]Meisinger (2006) [77]Folsom (2000) [19]Meisinger (2006) [77]Carey (1997) [78]Oguma (2005) [81]Meisinger (2006) [77]Wannamethee (2005) [79]Oguma (2005) [81]Meisinger (2006) [77]Koh-Banerjee (2004) [80]Wannamethee (2005) [79]Meisinger (2006) [77]Wang (2005) [82]Meisinger (2006) [77]Wang (2005) [82]BMIBMIBMIBMIBMIBMIWCWCWCWCBMIBMIBMIBMIBMIBMIBMIWCWCWCWCFFFFFFFFFFMMMMMMMMMMM35-7445+35-7455-6945+30-5535-7455-6935-7430-5535-7440-5935-7440-7540-5935-7440-7535-7440-759.56.99.59.46.9169.59.49.57.623.89.517.623.89.53.717.69.5139.513GermanyUSGermanyUSUSUSGermanyUSGermanyUSUSGermanyUKUSGermanyUSUKGermanyUSGermanyUS29573787829573170237878849412957317022957424922018730557176201873055221727176305527270305527270RR-PRR-PIRRIRRIRRIRRRR-PIRRIRRIRRRR-PRR-PRR-PIRRIRRIRRIRRRR-PRR-PIRRIRRStudy Obesity Sex Age F-up Country N OutcomeIRR:IRR:IRR:RR-P:IRR:RR-P:IRR:IRR:IRR:IRR:RR-P:IRR:RR-P:IRR:US studies (3)F-up>=8 yrs (3)F-up<8 yrs (1)All studies (2)All studies (4)All studies (1)All studies (3)US studies (2)F-up>=10 yrs (2)F-up<10 yrs (2)All studies (3)All studies (4)All studies (2)All studies (2)24.9(0)*25.1(0)*0.8(0.37)*26.2(0)*15.4(0)*1.4(0.24)*2.3(0.13)*0.4(0.53)*2.9(0.23)*3.2(0.37)*3.8(0.05)*3.3(0.07)*OverweightRRRisk Est (95% CI)3.12  (1.90  - 5.11 )3.97  (3.34  - 4.72 )3.26  (1.97  - 5.39 )3.27  (2.77  - 3.85 )4.01  (3.37  - 4.78 )5.47  (4.82  - 6.22 )2.80  (1.67  - 4.70 )2.63  (2.12  - 3.26 )2.99  (1.76  - 5.05 )4.85  (3.89  - 6.06 )2.11  (1.88  - 2.36 )2.16  (1.36  - 3.43 )2.63  (2.09  - 3.32 )2.19  (1.95  - 2.47 )2.20  (1.37  - 3.53 )2.63  (1.99  - 3.46 )2.69  (2.12  - 3.40 )1.81  (1.26  - 2.60 )2.72  (2.24  - 3.31 )1.87  (1.29  - 2.71 )2.77  (2.27  - 3.37 )4.17  (3.24  - 5.37 )3.88  (2.84  - 5.28 )4.01  (3.37  - 4.78 )3.64  (2.93  - 4.52 )3.92  (3.10  - 4.97 )2.80  (1.67  - 4.70 )3.40  (2.42  - 4.78 )2.34  (2.03  - 2.71 )2.28  (2.06  - 2.54 )2.51  (1.98  - 3.19 )2.29  (1.98  - 2.64 )2.40  (2.12  - 2.72 )2.27  (1.67  - 3.10 )2.36  (1.76  - 3.15 )0.5 1 2 4 160.5 1 2 4 16ObeseRRRisk Est (95% CI)7.41  (4.81  - 11.42)12.83 (10.93 - 15.07)8.34  (5.37  - 12.97)9.49  (8.09  - 11.14)13.47 (11.45 - 15.86)19.58 (17.37 - 22.06)8.39  (5.38  - 13.09)8.88  (7.49  - 10.52)9.81  (6.23  - 15.43)15.26 (12.43 - 18.72)4.56  (3.74  - 5.56 )5.53  (3.52  - 8.68 )6.46  (4.97  - 8.40 )5.60  (4.51  - 6.97 )6.10  (3.84  - 9.69 )8.79  (6.34  - 12.19)7.12  (5.40  - 9.40 )4.07  (3.02  - 5.48 )6.16  (5.26  - 7.21 )4.67  (3.43  - 6.38 )6.47  (5.51  - 7.60 )13.60 (9.70  - 19.07)11.96 (7.79  - 18.37)13.47 (11.45 - 15.86)10.47 (7.31  - 15.00)12.41 (9.03  - 17.06)8.39  (5.38  - 13.09)11.10 (8.23  - 14.96)6.84  (4.96  - 9.43 )6.14  (5.17  - 7.29 )7.78  (5.96  - 10.16)5.36  (4.32  - 6.65 )6.74  (5.55  - 8.19 )5.13  (3.81  - 6.90 )5.67  (4.46  - 7.20 )0.5 1 2 4 16 320.5 1 2 4 16 32Meta-analysis of studies for hypertensionFigure 11Meta-analysis of studies for hypertension. *Q-statistic(p-value); F-up is follow-up in years; square shape: study- and gen-der- specific risk estimates; diamond shape: pooled risk estimates.Radi (2004) [84]Hu (2004) [83]Folsom (2000) [19]Huang (1998) [85]Folsom (2000) [19]Radi (2004) [84]Hu (2004) [83]BMIBMIBMIBMIWCBMIBMIFFFFFMM15-6925-6455-6930-5555-6915-6925-641115.9165.9111FranceFinlandUSUSUSFranceFinland7774913931702824733170296918302RR-PIRRIRRIRRIRRRR-PIRRStudy ObesitySex Age F-up Country N OutcomeIRR & RR-P:IRR:IRR & RR-P:IRR:IRR:IRR:RR-P:IRR:IRR:RR-P:IRR:Europe studies (2)US studies (2)min.age<55 (3)min.age>=55 (1)min.age<55 (2)F-up>=10 yrs (2)All studies (1)All studies (3)All studies (1)All studies (1)All studies (1)2.6(0.11)*148.3(0)*40.3(0)*40.1(0)*40.1(0)*175.6(0)*OverweightRRRisk Est (95% CI)2.04  (1.33  - 3.12 )1.40  (1.20  - 1.63 )1.44  (1.34  - 1.54 )2.32  (2.25  - 2.40 )1.38  (1.27  - 1.51 )2.34  (1.85  - 2.98 )1.28  (1.09  - 1.50 )1.64  (1.24  - 2.18 )1.83  (1.31  - 2.55 )1.89  (1.45  - 2.46 )1.44  (1.34  - 1.54 )1.81  (1.27  - 2.57 )1.81  (1.27  - 2.57 )2.04  (1.33  - 3.12 )1.65  (1.24  - 2.19 )1.38  (1.27  - 1.51 )2.34  (1.85  - 2.98 )1.28  (1.10  - 1.50 )0.5 1 2 4 160.5 1 2 4 16ObeseRRRisk Est (95% CI)3.48  (2.12  - 5.71 )1.59  (1.32  - 1.93 )2.06  (1.89  - 2.24 )4.01  (3.83  - 4.19 )1.90  (1.77  - 2.03 )5.93  (4.39  - 8.00 )1.84  (1.51  - 2.24 )2.23  (1.30  - 3.83 )2.88  (1.81  - 4.57 )2.76  (1.72  - 4.45 )2.06  (1.89  - 2.24 )2.54  (1.34  - 4.82 )2.54  (1.34  - 4.82 )3.48  (2.12  - 5.71 )2.42  (1.59  - 3.67 )1.90  (1.77  - 2.03 )5.93  (4.39  - 8.00 )1.84  (1.51  - 2.24 )0.5 1 2 4 16 320.5 1 2 4 16 32BMC Public Health 2009, 9:88 http://www.biomedcentral.com/1471-2458/9/88Colorectal cancerA total of 12 studies were identified for colorectal cancer(Figures 5 and 6) [19,42,45,54-62]. For men, the pooledIRRs [95% CI] across categories of WC were 1.88 [1.47–2.41] for overweight and 2.93 [2.31–3.73] for obesity andacross categories of BMI were 1.51 [1.37–1.67] for over-weight and 1.95 [1.59–2.39] for obesity. For women, thepooled IRRs across categories of WC were 1.25 [0.98–1.59] for overweight and 1.55 [1.27–1.88] for obesity andthose across categories of BMI were 1.45 [1.30–1.62] foroverweight and 1.66 [1.52–1.81] for obesity.Esophageal cancerOnly 1 study was identified for esophageal cancer [63].The study found the risk of cancer based on overweight tobe 1.15 [0.97–1.36] and 1.13 [1.02–1.26] for females andmales, respectively. The corresponding risks for obesitywere 1.20 [0.95–1.53] and 1.21 [0.97–1.52].Kidney cancerWe identified 5 studies meeting the inclusion criteriarelating overweight and obesity to kidney cancer (Figure7) [42,45,57,64,65]. The pooled IRRs [95% CI] across cat-egories of BMI for men were 1.40 [1.31–1.49] for over-weight and 1.82 [1.61–2.05] for obesity. For women thePancreatic cancerThe search identified 6 studies giving information on therisk of pancreatic cancer attributable to overweight andobesity (Figure 8) [42,45,66-69]. The pooled IRRs [95%CI] across categories of BMI for men were 1.28 [0.94–1.75] for overweight and 2.29 [1.65–3.19] for obesity. Forwomen the corresponding risks were 1.24 [0.98–1.56]and 1.60 [1.17–2.20].Prostate cancerThe search identified 8 studies giving information on therisk of prostate cancer attributable to overweight andobesity (Figure 9) [36,42,45,70-74]. The pooled IRRs[95% CI] across categories of BMI were 1.14 [1.00–1.31]for overweight and 1.05 [0.85–1.30] for obesity.Type II diabetesNine studies met the inclusion criteria and were includedin the meta-analysis (Figure 10) [19,75-82]. In general,elevated BMI and WC were significantly associated withtype II diabetes in men and women. The pooled IRRs[95% CI] across categories of BMI were 2.40 [2.12–2.72]and 6.74 [5.55–8.19] in men while the correspondingIRRs in women were 3.92 [3.10–4.97] and 12.41 [9.03–17.06]. The association between increased WC and type IIMeta-analysis of studies for strokeFigure 12Meta-analysis of studies for stroke. *Q-statistic(p-value); F-up is follow-up in years; square shape: study- and gender- spe-cific risk estimates; diamond shape: pooled risk estimates.Murphy (2006) [89]Kurth (2005) [92]Wessel (2004) [91]Rexrode (1997) [90]Murphy (2006) [89]Shaper (1997) [88]Jood (2004) [87]Kurth (2002) [86]Kurth (2002) [86]BMIBMIBMIBMIBMIBMIBMIBMIBMIFFFFMMMMM45-6445+30-5545-6440-5947-5540-8440-84209.83.914.72014.822.812.512.5UKUSUSUSUKUKSwedenUSUS835439876906874377048773574022141421414RR-PRR-PRR-PIRRRR-PRR-PRR-PRR-PIRRStudy ObesitySex Age F-up Country N OutcomeIRR & RR-P:RR-P:RR-P:IRR & RR-P:RR-P:IRR:RR-P:RR-P:IRR:US studies (3)US studies (2)F-up>=9 yrs (2)F-up>=10 yrs (3)All studies (3)All studies (1)Europe studies (3)All studies (4)All studies (1)2.1(0.34)*2.1(0.15)*0.4(0.51)*1.3(0.52)*2.9(0.24)*0.9(0.64)*3.5(0.32)*OverweightRRRisk Est (95% CI)1.09  (0.91  - 1.31 )1.20  (0.97  - 1.48 )2.69  (0.91  - 7.94 )1.29  (1.03  - 1.62 )1.07  (0.89  - 1.29 )1.19  (0.93  - 1.52 )1.19  (1.04  - 1.36 )1.34  (1.16  - 1.55 )1.34  (1.16  - 1.56 )1.26  (1.08  - 1.47 )1.24  (1.00  - 1.52 )1.13  (0.99  - 1.31 )1.18  (1.04  - 1.32 )1.15  (1.00  - 1.32 )1.29  (1.03  - 1.62 )1.16  (1.05  - 1.28 )1.23  (1.13  - 1.34 )1.34  (1.16  - 1.56 )0.5 1 2 4 160.5 1 2 4 16ObeseRRRisk Est (95% CI)1.60  (1.30  - 1.98 )1.32  (1.03  - 1.69 )2.05  (0.68  - 6.16 )1.50  (1.27  - 1.77 )1.35  (1.03  - 1.78 )1.37  (0.94  - 2.01 )1.57  (1.28  - 1.92 )1.66  (1.27  - 2.18 )1.68  (1.27  - 2.21 )1.45  (1.27  - 1.66 )1.35  (1.06  - 1.71 )1.48  (1.26  - 1.73 )1.49  (1.33  - 1.67 )1.49  (1.27  - 1.74 )1.50  (1.27  - 1.77 )1.47  (1.26  - 1.71 )1.51  (1.33  - 1.72 )1.68  (1.27  - 2.21 )0.5 1 2 4 16 320.5 1 2 4 16 32Page 10 of 20(page number not for citation purposes)corresponding risks were 1.82 [1.68–1.98] and 2.64[2.39–2.90].diabetes was similar but weaker in comparison with BMI.Only two studies were included in men. The pooled IRRsBMC Public Health 2009, 9:88 http://www.biomedcentral.com/1471-2458/9/88[95% CI] across categories of WC were 2.36 [1.76–3.15]and 5.67 [4.46–7.20] in men and the pooled RR-Ps [95%CI] based on the same two studies were 2.27 [1.67–3.10]and 5.13 [3.81–6.90], respectively. The pooled RR-Ps weremore conservative RR estimates and presented in the sum-mary table (Table 2). The pooled IRRs [95% CI] across cat-egories of WC were 3.40 [2.42–4.78] and 11.10 [8.23–14.96] in women.HypertensionFour studies met the inclusion criteria and were includedin the meta-analysis (Figure 11) [19,83-85]. The pooledIRR [95% CI] estimates for hypertension across categoriesBMI for men were 1.28 [1.10–1.50] for overweight and1.84 [1.51–2.24] for obesity. The corresponding figuresfor females were 1.65 [1.24–2.19] and 2.42 [1.59–3.67].The single IRR estimate based on WC for women was 1.38[1.27–1.51] for overweight and 1.90 [1.77–2.03] for obes-ity.StrokeSeven studies met the inclusion criteria and were includedin the meta-analysis (Figure 12) [86-92]. The pooled RR-P [95% CI] estimates for stroke across categories BMI for[1.33–1.72] for obesity. The corresponding results forfemales were 1.15 [1.00–1.32] and 1.49 [1.27–1.74].Coronary Artery DiseaseEleven studies were identified with evidence for coronaryartery disease related to obesity (Figures 13 and 14)[20,21,79,91,93-99]. The pooled RR-P estimates for coro-nary artery disease across categories of WC were more con-servative RR estimates for men than the correspondingIRR estimates and thus were presented in the summarytable (Table 2). The RR-P [95% CI] estimates for WC were1.41 [1.16–1.72] for overweight and 1.81 [1.45–2.25] forobesity. The corresponding results for BMI were 1.29[1.18–1.41] and 1.72 [1.51–1.96]. While the pooled RR-Pestimates based on BMI measurements for women weregenerated from 4 studies, the IRR estimates were gener-ated from 2 different studies with longer follow-up. Thus,the IRR estimates were the RR estimates for women pre-sented in the summary table (Table 2). The estimates were1.80 [1.64–1.98] for overweight and 3.10 [2.81–3.43] forobesity based on BMI measurements and 1.82 [1.41–2.36] and 2.69 [2.05–3.53] for WC.Congestive Heart FailureMeta-analysis of studies for coronary artery disease-femalesFigure 13Meta-analysis of studies for coronary artery disease-females. *Q-statistic(p-value); F-up is follow-up in years; square shape: study- and gender- specific risk estimates; diamond shape: pooled risk estimates.Wessel (2004) [91]Seeman (1993) [96]Tuomilehto (1987) [98]Kannel (2002) [97]Wilson (2002) [94]Li (2006) [99]Rexrode (1998) [20]Rexrode (1998) [20]BMIBMIBMIBMIBMIBMIWCWCFFFFFFFF65-9830-5930-7435-7534-5940-6540-653.96916442088USUSFinlandUSUSUSUSUS906126240372798433883934470244702RR-PRR-PRR-PRR-PIRRIRRRR-PIRRStudy Obesity Sex Age F-up Country N OutcomeIRR & RR-P:RR-P:IRR & RR-P:RR-P:RR-P:RR-P:IRR:RR-P:IRR:US studies (5)US studies (3)min.age<=40 (5)F-up>=10 yrs (1)F-up<10 yrs (3)All studies (4)All studies (2)All studies (1)All studies (1)10.7(0.03)*2.2(0.33)*5.8(0.21)*1.3(0.53)*2.4(0.49)*0.4(0.51)*OverweightRRRisk Est (95% CI)0.79  (0.27  - 2.30 )0.82  (0.44  - 1.53 )1.32  (0.69  - 2.51 )1.33  (0.93  - 1.91 )1.54  (0.97  - 2.46 )1.81  (1.65  - 1.99 )1.82  (1.40  - 2.36 )1.82  (1.41  - 2.36 )1.32  (1.02  - 1.71 )1.14  (0.85  - 1.54 )1.50  (1.25  - 1.80 )1.33  (0.93  - 1.91 )0.99  (0.66  - 1.50 )1.14  (0.88  - 1.48 )1.80  (1.64  - 1.98 )1.82  (1.40  - 2.36 )1.82  (1.41  - 2.36 )0.5 1 2 4 160.5 1 2 4 16ObeseRRRisk Est (95% CI)1.47  (0.58  - 3.72 )1.32  (0.76  - 2.30 )1.98  (0.99  - 3.94 )2.33  (1.60  - 3.39 )2.13  (1.25  - 3.65 )3.15  (2.84  - 3.48 )2.66  (2.03  - 3.49 )2.69  (2.05  - 3.53 )2.15  (1.59  - 2.91 )1.85  (1.33  - 2.58 )2.46  (1.96  - 3.09 )2.33  (1.60  - 3.39 )1.53  (1.04  - 2.27 )1.91  (1.45  - 2.50 )3.10  (2.81  - 3.43 )2.66  (2.03  - 3.49 )2.69  (2.05  - 3.53 )0.5 1 2 4 16 320.5 1 2 4 16 32Page 11 of 20(page number not for citation purposes)men were 1.23 [1.13–1.34] for overweight and 1.51 Four studies were identified with evidence for congestiveheart failure related to obesity (Figure 15) [91,100-102].BMC Public Health 2009, 9:88 http://www.biomedcentral.com/1471-2458/9/88The pooled IRR [95% CI] estimates for congestive heartfailure across categories of BMI for men were 1.31 [0.96–1.79] for overweight and 1.79 [1.24–2.59] for obesity. Thepooled RR-P estimates for females based on 3 studies were1.27 [0.68–2.37] and 1.78 [1.07–2.95], which were cho-sen as the RR estimates over the IRR estimates based on 2studies.AsthmaFour studies were identified with evidence for asthmarelated to obesity (Figure 16) [103-106]. The pooled RR-P[95% CI] estimates for asthma across categories of BMI formen were 1.20 [1.08–1.33] for overweight and 1.43[1.14–1.79] for obese. The corresponding numbers forfemales were 1.25 [1.05–1.49] and 1.78 [1.36–2.32].Chronic back painOnly 1 study was identified to meet the inclusion criteriafor chronic back pain [107]. The study identified the asso-ciation for the overweight and obesity with early retire-ment due to chronic back pain. The study found RR-P[95% CI] estimates across categories of BMI of chronicOsteoarthritisWe identified three studies meeting the inclusion criteriarelating overweight and obesity to osteoarthritis (Figure17) [108-110]. The studies identified the risk of jointreplacement attributable to being overweight and obese.The pooled IRRs [95% CI] across categories of BMI formen were 2.76 [2.05–3.70] for overweight and 4.20[2.76–6.41] for obesity. For women, the RR-P estimateswere more conservative RR estimate and they were 1.80[1.75–1.85] and 1.96 [1.88–2.04].Pulmonary embolismOnly 1 study was identified to meet the inclusion criteriafor pulmonary embolism [111]. The study found IRR[95% CI] across categories of BMI of Pulmonary embo-lism based on overweight to be 1.91 [1.39–2.64] and forobesity 3.51 [2.61–4.73].Gallbladder diseaseWe identified four studies meeting the inclusion criteriarelating overweight and obesity gallbladder disease (Fig-ure 18) [59,112-114]. The pooled IRRs [95% CI] acrossMeta-analysis of studies for coronary artery disease-malesFigure 14Meta-analysis of studies for coronary artery disease-males. *Q-statistic(p-value); F-up is follow-up in years; square shape: study- and gender- specific risk estimates; diamond shape: pooled risk estimates.Tuomilehto (1987) [98]Kannel (2002) [97]Wannamethee (2005) [79]Jonsson (2002) [93]Seeman (1993) [96]St-Pierre (2005) [95]Wannamethee (2005) [79]Wilson (2002) [94]Jonsson (2002) [93]Rexrode (2001) [21]Rexrode (2001) [21]BMIBMIBMIBMIBMIBMIBMIBMIBMIWCWCMMMMMMMMMMM30-5930-7440-5927-6165-9834-6440-5935-7527-6140-8440-8491621.32361321.344233.93.9FinlandUSUKSwedenUSCanadaUKUSSwedenUSUS3785245371752202591618247175433220251616416164RR-PRR-PRR-PRR-PRR-PIRRIRRIRRIRRRR-PIRRStudy Obesity Sex Age F-up Country N OutcomeIRR & RR-P:IRR & RR-P:RR-P:RR-P:IRR:IRR:IRR & RR-P:RR-P:RR-P:RR-P:RR-P:RR-P:IRR:RR-P:IRR:Europe studies (3)US/Canada studies (4)Europe studies (3)US studies (2)Europe studies (2)US/Canada studies (2)max.age=<65 (4)max.age=<65 (3)min.age>=65 (1)F-up>=10 yrs (3)F-up<10 yrs (2)All studies (5)All studies (4)All studies (1)All studies (1)8(0.09)*5.9(0.11)*6(0.05)*3.7(0.06)*1.4(0.24)*2(0.16)*12.5(0.03)*6(0.05)*5.1(0.08)*4.6(0.03)*10.1(0.04)*6.5(0.09)*OverweightRRRisk Est (95% CI)0.98  (0.69  - 1.39 )1.12  (0.89  - 1.41 )1.26  (1.16  - 1.37 )1.41  (1.28  - 1.56 )2.20  (1.15  - 4.22 )1.01  (0.79  - 1.30 )1.31  (1.19  - 1.44 )1.42  (0.95  - 2.11 )1.42  (1.29  - 1.57 )1.41  (1.16  - 1.72 )1.43  (1.17  - 1.75 )1.34  (1.26  - 1.44 )1.16  (1.00  - 1.35 )1.31  (1.19  - 1.43 )1.21  (0.97  - 1.50 )1.36  (1.27  - 1.46 )1.11  (0.90  - 1.38 )1.24  (1.08  - 1.42 )1.31  (1.19  - 1.43 )2.20  (1.15  - 4.22 )1.29  (1.18  - 1.42 )1.33  (0.78  - 2.24 )1.29  (1.18  - 1.41 )1.28  (1.14  - 1.45 )1.41  (1.16  - 1.72 )1.43  (1.17  - 1.75 )0.5 1 2 4 160.5 1 2 4 16ObeseRRRisk Est (95% CI)1.74  (1.21  - 2.50 )1.50  (1.13  - 1.98 )1.62  (1.44  - 1.83 )1.99  (1.71  - 2.32 )1.98  (0.96  - 4.08 )1.26  (0.88  - 1.80 )1.79  (1.54  - 2.08 )1.73  (1.04  - 2.91 )2.08  (1.77  - 2.45 )1.81  (1.45  - 2.25 )1.86  (1.49  - 2.32 )1.90  (1.71  - 2.12 )1.48  (1.22  - 1.80 )1.76  (1.53  - 2.02 )1.55  (1.20  - 2.01 )1.92  (1.72  - 2.14 )1.40  (1.04  - 1.88 )1.72  (1.43  - 2.06 )1.76  (1.53  - 2.02 )1.98  (0.96  - 4.08 )1.71  (1.47  - 1.98 )1.83  (1.31  - 2.54 )1.72  (1.51  - 1.96 )1.75  (1.44  - 2.12 )1.81  (1.45  - 2.25 )1.86  (1.49  - 2.32 )0.5 1 2 4 16 320.5 1 2 4 16 32Page 12 of 20(page number not for citation purposes)back pain based on overweight to be 1.59 [1.34–1.89] andfor obesity 2.81 [2.27–3.48].categories of WC for men were 1.63 [1.42–1.88] for over-weight and 2.51 [2.16–2.91] for obesity. The correspond-BMC Public Health 2009, 9:88 http://www.biomedcentral.com/1471-2458/9/88ing pooled RR-Ps were 1.61 [1.40–1.85] and 2.38 [2.06–2.75]. Thus, the pooled RR-Ps were more conservative RRestimates and presented in Table 2. Across categories ofBMI, the pooled IRR and RR-P estimates were presented asthe RR estimates in Table 2 and they were 1.09 [0.87–1.37] for overweight and 1.43 [1.04–1.96] for obesity. Forwomen only estimates for BMI were identified givingpooled IRR and RR-P estimates of 1.44 [1.05–1.98] foroverweight and 2.32 [1.17–4.57] for obesity.Potential publication bias was assessed for post-meno-pausal breast cancer, endometrial cancer, ovarian cancer,colorectal cancer, pancreatic cancer for females and pros-tate cancer. We found some evidence of funnel-plot asym-metry for obesity in prostate cancer where bigger studiestended to show stronger positive association than smallerstudies. No evidence of publication bias was found in theother meta-analyses.Our sensitivity analyses showed that our results were ingeneral robust with the following exceptions. For ovariancancer, associations for both overweight and obesity wereslightly weaker in US studies compared to European stud-ies. Similar country differences were found in pancreaticcancers; in addition, weaker associations were observed inolder population. Studies with shorter follow-up time andof older population showed slightly weaker association ofobesity with prostate cancer. In coronary artery disease forfemales, studies with shorter follow-up showed weakerassociations of both overweight and obese. In coronaryartery disease for males, weaker associations wereobserved in US and Canadian studies. Studies of post-menopausal and senior women on congestive heart fail-ure showed weaker associations for both overweight andobesity.DiscussionWe have comprehensively reviewed 20 co-morbidities forhigh quality cohort studies which determine risk factorsassociated with overweight or obesity. 18 co-morbiditieswere identified and meta-analysis was performed where atleast 1 study was found. A summary of the results can befound in Table 2.There are a number of alternative meta-analyses withwhich we can compare our results. For example, recentmeta-analyses have been reported in diabetes [115,116],cardiovascular diseases [117], coronary heart disease[118], hypertension [116], cancer [119], colorectal cancer[120-122], gallbladder cancer [123], pancreatic cancer[124], ovarian cancer [125] and asthma [126]. However,each study uses different definitions of overweight andobesity, includes varying quality of study designs, uses dif-ferent methods for meta-analysis and ultimately onlyfocuses on individual co-morbidities. Hence, the objec-tive of our study is not only to provide up to date esti-mates of the risk of all possible co-morbiditiesattributable to overweight and obesity, but also to do itusing consistent definitions and methodology.In assessing whether obesity is related to a given co-mor-bidity, the occurrence timing of co-morbidities withrespect to exposure of obesity is important in determiningthe causal pathway. Therefore, we included only the pro-Meta-analysis of studies for congestive heart failureFigure 15Meta-analysis of studies for congestive heart failure. *Q-statistic(p-value); **post-menopause; square shape: study- and Wessel (2004) [91]Bibbins-Domingo (2004) [102]Kenchaiah (2002) [101]Rea (2003) [100]Kenchaiah (2002) [101]Kenchaiah (2002) [101]Kenchaiah (2002) [101]BMIBMIBMIBMIBMIBMIBMIFFFFFMMPost-M**30+65+30+30+30+3.96.3147.3141414USUSUSUSUSUSUS906239131773223317727042704RR-PRR-PRR-PIRRIRRRR-PIRRStudy Obesity Sex Age F-up Country N OutcomeIRR & RR:RR-P:IRR:RR-P:IRR:post-menopause and 65+ (2)All studies (3)All studies (2)All studies (1)All studies (1)0.6(0.45)*16.8(0)*18.2(0)*OverweightRRRisk Est (95% CI)0.63  (0.30  - 1.30 )1.21  (0.87  - 1.70 )2.38  (1.81  - 3.14 )1.03  (0.79  - 1.34 )2.41  (1.81  - 3.21 )1.36  (1.01  - 1.83 )1.31  (0.96  - 1.79 )1.10  (0.89  - 1.35 )1.27  (0.68  - 2.37 )1.57  (0.86  - 2.87 )1.36  (1.01  - 1.83 )1.31  (0.96  - 1.79 )0.1 0.5 1 2 4 160.1 0.5 1 2 4 16ObeseRRRisk Est (95% CI)0.96  (0.51  - 1.83 )1.77  (1.28  - 2.43 )2.91  (2.14  - 3.95 )1.39  (1.04  - 1.84 )3.08  (2.23  - 4.25 )1.80  (1.27  - 2.56 )1.79  (1.24  - 2.59 )1.54  (1.25  - 1.90 )1.78  (1.07  - 2.95 )2.06  (1.16  - 3.66 )1.80  (1.27  - 2.56 )1.79  (1.24  - 2.59 )0.1 0.5 1 2 4 16 320.1 0.5 1 2 4 16 32Page 13 of 20(page number not for citation purposes)gender- specific risk estimates; diamond shape: pooled risk estimates.BMC Public Health 2009, 9:88 http://www.biomedcentral.com/1471-2458/9/88Page 14 of 20(page number not for citation purposes)Meta-analysis of studies for osteoarthritisFigure 17Meta-analysis of studies for osteoarthritis. *Q-statistic(p-value); F-up is follow-up in years; square shape: study- and gen-der- specific risk estimates; diamond shape: pooled risk estimates.Karlson (2003) [110]Flugsrud (2006) [109]Karlson (2003) [110]Flugsrud (2006) [109]Flugsrud (2006) [109]Flugsrud (2006) [109]Jarvholm (2005) [108]BMIBMIBMIBMIBMIBMIBMIFFFFMMM30-5518-6730-5518-6718-6718-6715-677.313.87.313.813.813.810.7USNorwayUSNorwayNorwayNorwaySweden9344262503493442625034526972526972320192RR-PRR-PIRRIRRRR-PIRRIRRStudy Obesity Sex Age F-up Country N OutcomeRR-P:IRR:RR-P:IRR:All studies (2)All studies (2)All studies (1)All studies (2)1(0.31)*13.9(0)*63.5(0)*OverweightRRRisk Est (95% CI)1.63  (1.34  - 1.97 )1.80  (1.75  - 1.86 )1.42  (1.17  - 1.73 )2.07  (2.01  - 2.14 )2.01  (1.92  - 2.09 )2.24  (2.14  - 2.34 )3.42  (3.11  - 3.76 )1.80  (1.75  - 1.85 )1.75  (1.35  - 2.26 )2.01  (1.92  - 2.09 )2.76  (2.05  - 3.70 )0.5 1 2 4 160.5 1 2 4 16ObeseRRRisk Est (95% CI)2.33  (1.89  - 2.86 )1.95  (1.87  - 2.03 )1.87  (1.52  - 2.30 )2.52  (2.42  - 2.63 )2.47  (2.27  - 2.70 )3.12  (2.86  - 3.40 )5.70  (4.90  - 6.62 )1.96  (1.88  - 2.04 )2.19  (1.77  - 2.71 )2.47  (2.27  - 2.70 )4.20  (2.76  - 6.41 )0.5 1 2 4 16 320.5 1 2 4 16 32Meta-analysis of studies for asthmaFigure 16Meta-analysis of studies for asthma. *Q-statistic(p-value); F-up is follow-up in years; square shape: study- and gender- spe-cific risk estimates; diamond shape: pooled risk estimates.Nystad (2004) [104]Ford (2004) [105]Chen (2002) [103]Camargo (1999) [106]Nystad (2004) [104]Ford (2004) [105]Nystad (2004) [104]Chen (2002) [103]Nystad (2004) [104]BMIBMIBMIBMIBMIBMIBMIBMIBMIFFFFFMMMM14-5925-7420-6426-4614-5925-7414-5920-6414-59211024211021221NorwayUSCanadaUSNorwayUSNorwayCanadaNorway68682583546798591168682362166723424166723RR-PRR-PRR-PRR-PIRRRR-PRR-PRR-PIRRStudy Obesity Sex Age F-up Country N OutcomeRR-P:RR-P:RR-P:RR-P:IRR:RR-P:RR-P:RR-P:RR-P:IRR:US/Canada studies (3)F-up>=10 yrs (2)F-up<10 yrs (2)All studies (4)All studies (1)US/Canada studies (2)F-up>=10 yrs (2)F-up<10 yrs (1)All studies (3)All studies (1)4.2(0.12)*0.2(0.7)*1.2(0.27)*22.6(0)*0.6(0.46)*1(0.31)*1.1(0.58)*OverweightRRRisk Est (95% CI)1.07  (0.97  - 1.18 )1.14  (0.84  - 1.56 )1.22  (0.81  - 1.85 )1.56  (1.38  - 1.76 )1.25  (1.13  - 1.38 )0.97  (0.63  - 1.48 )1.22  (1.09  - 1.36 )1.29  (0.69  - 2.41 )1.53  (1.37  - 1.71 )1.34  (1.11  - 1.63 )1.08  (0.98  - 1.19 )1.53  (1.36  - 1.72 )1.25  (1.05  - 1.49 )1.25  (1.13  - 1.38 )1.06  (0.75  - 1.51 )1.20  (1.08  - 1.33 )1.29  (0.69  - 2.41 )1.20  (1.08  - 1.33 )1.53  (1.37  - 1.71 )0.1 0.5 1 2 4 160.1 0.5 1 2 4 16ObeseRRRisk Est (95% CI)1.40  (1.19  - 1.65 )1.39  (1.00  - 1.93 )2.05  (1.33  - 3.17 )2.51  (2.23  - 2.82 )1.87  (1.58  - 2.21 )1.50  (0.88  - 2.56 )1.53  (1.17  - 1.99 )0.76  (0.35  - 1.63 )2.19  (1.68  - 2.87 )1.96  (1.46  - 2.63 )1.40  (1.21  - 1.62 )2.47  (2.21  - 2.77 )1.78  (1.36  - 2.32 )1.87  (1.58  - 2.21 )1.20  (0.78  - 1.86 )1.52  (1.20  - 1.93 )0.76  (0.35  - 1.63 )1.43  (1.14  - 1.79 )2.19  (1.68  - 2.87 )0.1 0.5 1 2 4 16 320.1 0.5 1 2 4 16 32BMC Public Health 2009, 9:88 http://www.biomedcentral.com/1471-2458/9/88spective cohort studies and excluded the cross-sectionalstudies and case control studies to minimize the associ-ated potential biases. In addition, WC measurements wereconsidered to be the better risk predictor for type II diabe-tes, hypertension, coronary artery disease, congestiveheart failure, stroke and gallbladder disease [16-24]. Inour studies, the risk for type II diabetes, female hyperten-sion, coronary artery disease, and male gallbladder dis-ease were estimated based on WC measurements.Some limitations are worthy of further consideration.Firstly, other variables not included in our analysis mightpotentially confound our results. Most important is theexclusion of the level of physical inactivity which is aknown risk factor for some co-morbidities and related tooverweight and obesity [127]. Physical inactivity is oftenpoorly reported and requiring its inclusion would havereduced the number of included studies. Secondly, for cer-tain co-morbidities, we only identified 1 or 2 prospectivecohort studies that adopted the WC measurements as therisk predictor. Further studies are required to determinethe association between WC and some co-morbiditiesbefore an estimate of the risk can be calculated through ameta-analysis. Thirdly, given the sizable literature andthat we were searching for non RCT studies for whichsearch filters are more complex, we determined to useMedline and Embase as the electronic databases, andcomplement the search with checking reference lists andSIS. Therefore, bias might have occurred due to our searchstrategy. However, given the nature of the studies we arelooking for, i.e., prospective cohort studies with highquality, we consider our search within Medline andEmbase sufficient. Lastly, due to the small number ofstudies for most co-morbidities, assessment of potentialpublication bias was infeasible. However, we did not findevidence of publication bias in those meta-analyses wherethe number of studies was relatively large except for pros-tate cancer.ConclusionIn conclusion, this study provides a comprehensive esti-mate of the incidence of 18 co-morbidities attributable tooverweight and obesity using standardized and consistentdefinitions and methodologies. Our findings confirm thatoverweight and obesity carry a profound health burdenand will have a significant impact on health expenditures.AbbreviationsWC: Waist Circumference; BMI: Body Mass Index; RR: Rel-ative Risk; IRR: Incidence Rate Ratio; RR-P: Relative Riskcalculated from the ratio of Proportions; CI: ConfidenceInterval; WHO: World Health Organization.Competing interestsThis manuscript is part of larger project funded by sanofi-aventis Canada Inc.Meta-analysis of studies for gallbladder diseaseFigure 18Meta-analysis of studies for gallbladder disease. *Q-statistic(p-value); F-up is follow-up in years; square shape: study- and gender- specific risk estimates; diamond shape: pooled risk estimates.Boland (2002) [113]Engeland (2005) [59]Layde (1982) [114]Boland (2002) [113]Engeland (2005) [59]Tsai (2004) [112]Tsai (2004) [112]Tsai (2004) [112]BMIBMIBMIBMIBMIBMIWCWCFFFMMMMM45-6420-7425-3945-6420-7440-7540-7540-758.223.79.18.223.78.98.98.9USNorwayUKUSNorwayUSUSUS69341037077170325839962901298472984729847RR-PIRRIRRRR-PIRRIRRRR-PIRRStudy Obesity Sex Age F-up Country N OutcomeIRR & RR-P:RR-P:IRR:IRR & RR-P:IRR & RR-P:RR-P:IRR:RR-P:IRR:All studies (3)All studies (1)All studies (2)US studies (2)All studies (3)All studies (1)All studies (2)All studies (1)All studies (1)9.8(0.01)*9(0)*3.9(0.05)*10.1(0.01)*8(0.01)*OverweightRRRisk Est (95% CI)1.20  (0.90  - 1.61 )1.27  (1.10  - 1.47 )2.15  (1.57  - 2.94 )0.91  (0.62  - 1.34 )1.00  (0.84  - 1.17 )1.37  (1.20  - 1.56 )1.61  (1.40  - 1.85 )1.63  (1.42  - 1.88 )1.44  (1.05  - 1.98 )1.20  (0.90  - 1.61 )1.64  (1.11  - 2.40 )1.15  (0.86  - 1.54 )1.09  (0.87  - 1.37 )0.91  (0.62  - 1.34 )1.18  (0.94  - 1.48 )1.61  (1.40  - 1.85 )1.63  (1.42  - 1.88 )0.5 1 2 4 160.5 1 2 4 16ObeseRRRisk Est (95% CI)1.24  (0.92  - 1.68 )1.88  (1.60  - 2.21 )5.36  (3.43  - 8.38 )0.95  (0.60  - 1.50 )1.38  (1.01  - 1.89 )1.94  (1.64  - 2.28 )2.38  (2.06  - 2.75 )2.51  (2.16  - 2.91 )2.32  (1.17  - 4.57 )1.24  (0.92  - 1.68 )3.08  (1.49  - 6.36 )1.42  (0.87  - 2.33 )1.43  (1.04  - 1.96 )0.95  (0.60  - 1.50 )1.67  (1.29  - 2.16 )2.38  (2.06  - 2.75 )2.51  (2.16  - 2.91 )0.5 1 2 4 16 320.5 1 2 4 16 32Page 15 of 20(page number not for citation purposes)thorough searching the internet. We did not search otherdatabases such as CINHAL, HealthSTAR, AMED, and BIO-BMC Public Health 2009, 9:88 http://www.biomedcentral.com/1471-2458/9/88Table 2: Relative co-morbidity risks related to being overweight or obeseCo-morbidity Measure Overweight ObesityMale Female Male FemaleType II Diabetes* BMI 2.40 (2.12–2.72) 3.92 (3.10–4.97) 6.74 (5.55–8.19) 12.41 (9.03–17.06)WC 2.27 (1.67–3.10)† 3.40 (2.42–4.78) 5.13 (3.81–6.90)† 11.10 (8.23–14.96)CancerBreast, Postmenopausal BMI - 1.08 (1.03–1.14) - 1.13 (1.05–1.22)Colorectal BMI 1.51 (1.37–1.67) 1.45 (1.30–1.62) 1.95 (1.59–2.39) 1.66 (1.52–1.81)Endometrial BMI - 1.53 (1.45–1.61) - 3.22 (2.91–3.56)Esophageal BMI 1.13 (1.02–1.26) 1.15 (0.97–1.36) 1.21 (0.97–1.52) 1.20 (0.95–1.53)Kidney BMI 1.40 (1.31–1.49) 1.82 (1.68–1.98) 1.82 (1.61–2.05) 2.64 (2.39–2.90)Ovarian BMI - 1.18 (1.12–1.23) - 1.28 (1.20–1.36)Pancreatic BMI 1.28 (0.94–1.75) 1.24 (0.98–1.56) 2.29 (1.65–3.19) 1.60 (1.17–2.20)Prostate BMI 1.14 (1.00–1.31) - 1.05 (0.85–1.30) -Cardiovascular DiseasesHypertension* BMI 1.28 (1.10–1.50) 1.65 (1.24–2.19) 1.84 (1.51–2.24) 2.42 (1.59–3.67)WC NA 1.38 (1.27–1.51) NA 1.90 (1.77–2.03)Coronary Artery Disease* BMI 1.29 (1.18–1.41)† 1.80 (1.64–1.98) 1.72 (1.51–1.96)† 3.10 (2.81–3.43)WC 1.41 (1.16–1.72)† 1.82 (1.41–2.36) 1.81 (1.45–2.25)† 2.69 (2.05–3.53)Congestive Heart Failure* BMI 1.31 (0.96–1.79) 1.27 (0.68–2.37)† 1.79 (1.24–2.59) 1.78 (1.07–2.95)†Pulmonary Embolism BMI 1.91 (1.39–2.64) 1.91 (1.39–2.64) 3.51 (2.61–4.73) 3.51 (2.61–4.73)Stroke* BMI 1.23 (1.13–1.34)† 1.15 (1.00–1.32)† 1.51 (1.33–1.72)† 1.49 (1.27–1.74)†OtherAsthma BMI 1.20 (1.08–1.33)† 1.25 (1.05–1.49)† 1.43 (1.14–1.79)† 1.78 (1.36–2.32)†Gallbladder Disease* BMI 1.09 (0.87–1.37)‡ 1.44 (1.05–1.98)‡ 1.43 (1.04–1.96)‡ 2.32 (1.17–4.57)‡WC 1.61 (1.40–1.85)† NA 2.38 (2.06–2.75)† NAOsteoarthritis BMI 2.76 (2.05–3.70) 1.80 (1.75–1.85)† 4.20 (2.76–6.41) 1.96 (1.88–2.04)†Chronic Back Pain BMI 1.59 (1.34–1.89)† 1.59 (1.34–1.89)† 2.81 (2.27–3.48)† 2.81 (2.27–3.48)†Page 16 of 20(page number not for citation purposes)BMC Public Health 2009, 9:88 http://www.biomedcentral.com/1471-2458/9/88Authors' contributionsZA conducted literature search. 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