UBC Theses and Dissertations

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UBC Theses and Dissertations

Genetic variation in lymphocyte life and death genes and risk of non-Hodgkin lymphomas Schuetz, Johanna Maria 2011

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DH4GH(h(D$332.1(H"0%1(45G1##(H)*+,-*"=(PH(h(P-##$/2#"0(H)*+,-*"∗ =(!g`!9H;(h(!"0%$&"#(g-&1( #)*+,-*"`!2/-."59..-/$"'16(H)*+,-*"(;$..21(#)*+,-*"=(!GH(h(!"&'#1(G1##(#)*+,-*"=(FHH(h( F*"##(H)*+,-/)'$/(H)*+,-*"=(HKHhH)*+,-+#".*"/)'$/(H)*+,-*"=(!$./8(45/1##(h(!$./1##"&1-2.( !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! !6(!0&/!R."D+G&/F!S'(.G-*+R0Q!>=G!'*/!E.*0&/*!G/R'*'0/F!"#!G0'L+(LQ!\+0&!Ofe!G'SRD/G!HO[mI!L*'F/!O! >=!'(F![e!G'SRD/G!HO[mI!%E!L*'F/!M!'(F!f!>=V! ∗  [i! !  45/1##(#)*+,-*"=(!P(h(!)/-.$.(P2&%-$61.=(K;GH(h(K10$+,10"#(;5G1##(H)*+,-*"=(!$./8(;5/1##(h( !$./1##"&1-2.(;5/1##(#)*+,-*".  [g! !  $9;<7'RZRZ'!7>7'@?9?A@?A:@'@CEE96D'  (( (  L925.3#/-! C62! -,\>,/3,;D! !"#$% MI(BIVUME( &'()*% JU(BeVJRE( +&,$$% MQ(BceeeE( "-+% JR(BQcJbE(  :.--./+! *,4;-! I8U]( I8U]( RM8J]( Mc8U](  :.--./+!./! <%)-!$#>/;! 6#7B! 61!*,@ A#;./+!C/#/@ <%)-!:LE! 74+<%)-! <%)-!!!!!!!!!!!!!! ;.*,37.#/-! -,\>,/3./+! -1/#/19#>-D! <./+5,7#/-! ]!S"! &425#712,-! +,/#712,;! +,/#712,;! R8Q]( JI( Q(BIE( RU(BJe]E( RU(BJQ8e]E( MR( U( b( M8I]( MQ( Q(BUE( Rb(BIR]E( Q(BMQ8I]E( e( U( U( c8e]( MV( M(BRE( RR(Bcc]E( b(BJc]E( Rb( U( U( RM8R]( JV( RR(BIE( RJ(BUJ]E( RM(BUR8U]E( MI( U( U(  ! P-0(!"#$=(b(FSK.(:101(%1&-')+16(5(U(/,-.1&(".('"%FSK.("&6(J(/,-.1&(3-0(+2'"'$71(32&/'$-&"#(01#17"&/18( (  [h! !  Table 2.3. Regression analysis in European samples for all SNPs in selected subtypes Controls SNP N N RAD50_IVS4(+19)G/A G/G 384 100 G/A 187 53 A/A 27 7 G/A & A/A 214 RAD50_IVS7(-38)C/T C/C 568 153 C/T 34 9 T/T 1 0 C/T & T/T 35 9 RAD50_IVS22(+24)A/G A/A 546 137 A/G 54 25 G/G 1 1 A/G & G/G 55 26 RAD50_IVS22(+62)A/G A/A 601 161 A/G 2 2 G/G 0 0 NBS1_5(-905)T/C T/T 266 76 T/C 267 72 C/C 64 14  DLBCL OR (95% CI)  N  FL OR (95% CI)  N  MZ/MALT OR (95% CI)  p value  p value  p value  1 1.05 (0.72 - 1.54) 0.96 (0.40 - 2.30)  0.896 0.799 0.935  107 55 10  1 1.08 (0.74 - 1.58) 1.31 (0.61 - 2.81)  0.474 0.677 0.492  43 19 3 22  1 1.01 (0.57 - 1.80) 1.01 (0.58 - 1.76)  0.975 0.967  1 1.01 (0.47 - 2.17) 0.97 (0.45 - 2.08)  0.983 0.941  166 6 1 7  1 0.63 (0.26 - 1.53) 0.71 (0.31 - 1.64)  0.304 0.422  58 8 1 9  1 3.02 (1.28 - 7.14) 3.39 (1.48 - 7.75)  0.012 0.004  1 1.77 (1.05 - 2.96) 1.81 (1.09 - 3.01)  0.031 0.022  150 24 0 24  1 1.61 (0.96 - 2.71) 1.59 (0.94 - 2.67)  0.073 0.081  59 7 0 7  1 1.30 (0.55 - 3.04) 1.29 (0.55 - 3.02)  0.550 0.560  -  -  174 0 0  -  -  67 0 0  -  -  1 0.95 (0.66 - 1.37) 0.77 (0.41 - 1.46)  0.465 0.769 0.423  87 63 24  1 0.75 (0.51 - 1.08) 1.20 (0.70 - 2.06)  0.847 0.119 0.498  28 43 7  1 1.12 (0.65 - 1.93) 1.02 (0.42 - 2.48)  0.816 0.678 0.964 !!"  "  Controls SNP N N NBS1_5UTR_(352)_del(AGTA) AGTA/AGTA 524 138 AGTA/58 16 -/2 0 AGTA/- & -/60 16 NBS1_IVS3(+208)G/A G/G 241 66 G/A 277 76 A/A 78 19 NBS1_3UTR(+273)G/A G/G 268 78 G/A 263 73 A/A 63 11 NBS1_X2_(102)_G/A G/G 266 75 G/A 272 72 A/A 59 13 NBS1_X5_(553)_G/C G/G 255 76 G/C 270 72 C/C 57 12 NBS1_X13_(2016)_A/G A/A 247 74 A/G 265 70 G/G 55 10  DLBCL OR (95% CI)  p value  N  FL OR (95% CI)  p value  N  MZ/MALT OR (95% CI)  p value  1 1.06 (0.59 - 1.92) 1.03 (0.57 - 1.85)  0.839 0.929  137 18 3 21  1 1.08 (0.61 - 1.92) 1.23 (0.71 - 2.11)  0.785 0.461  60 2 0 2  1 0.30 (0.07 - 1.29) -  0.105 -  1 1.00 (0.68 - 1.45) 0.86 (0.48 - 1.52)  0.672 0.977 0.596  84 63 27  1 0.67 (0.46 - 0.97) 1.04 (0.62 - 1.72)  0.466 0.033 0.892  26 30 10  1 0.97 (0.56 - 1.71) 1.14 (0.52 - 2.51)  0.818 0.935 0.744  1 0.97 (0.68 - 1.40) 0.60 (0.24 - 1.19)  0.256 0.885 0.142  90 54 24  1 0.65 (0.44 - 0.95) 1.12 (0.66 - 1.91)  0.509 0.026 0.669  26 33 6  1 1.28 (0.74 - 2.23) 0.89 (0.35 - 2.29)  0.807 0.381 0.813  1 0.95 (0.66 - 1.37) 0.79 (0.41 - 1.53)  0.521 0.782 0.486  87 62 24  1 0.72 (0.50 - 1.04) 1.31 (0.76 - 2.25)  0.935 0.082 0.326  28 33 7  1 1.15 (0.67 - 1.97) 1.09 (0.45 - 2.67)  0.698 0.615 0.849  1 0.90 (0.62 - 1.30) 0.70 (0.36 - 1.39)  0.306 0.572 0.310  84 62 22  1 0.73 (0.50 - 1.06) 1.22 (0.70 - 2.13)  0.786 0.098 0.486  28 33 6  1 1.12 (0.65 - 1.92) 0.92 (0.36 - 2.36)  0.938 0.688 0.857  1 0.89 (0.61 - 1.30) 0.61 (0.29 - 1.26)  0.204 0.549 0.180  83 59 21  1 0.69 (0.47 - 1.01) 1.20 (0.68 - 2.12)  0.634 0.055 0.537  27 33 6  1 1.13 (0.65 - 1.95) 0.94 (0.36 - 2.43)  0.897 0.671 0.902 !"#  #  Controls SNP N N MRE11_5(-1703)A/G A/A 261 76 A/G 267 60 G/G 66 15 MRE11_5(-1456)C/T C/C 582 153 C/T 21 9 T/T 1 1 C/T & T/T 22 10 MRE11_IVS2(+28)G/A G/G 189 51 G/A 277 81 A/A 124 30 MRE11_IVS9(-60)A/T T/T 270 82 T/A 255 61 A/A 70 20 BLM_IVS7(+388)C/T C/C 517 140 C/T 78 22 T/T 3 0 C/T & T/T 81 22 BLM_IVS7(+798)ins(T) T/T 528 145 T/69 17 -/4 0 T/- & -/73 17  DLBCL OR (95% CI)  p value  N  FL OR (95% CI)  p value  N  MZ/MALT OR (95% CI)  p value  1 0.91 (0.63 - 1.32) 0.79 (0.42 - 1.47)  0.431 0.629 0.457  81 69 22  1 0.84 (0.58 - 1.21) 1.03 (0.59 - 1.78)  0.725 0.341 0.919  25 29 13  1 1.20 (0.68 - 2.13) 1.95 (0.93 - 4.10)  0.100 0.527 0.076  1 1.76 (0.78 - 3.96) 1.87 (0.86 - 4.08)  0.173 0.115  165 9 0 9  1 1.38 (0.61 - 3.09) 1.34 (0.60 - 2.99)  0.441 0.481  67 1 0 1  -  -  1 1.07 (0.72 - 1.59) 0.90 (0.54 - 1.49)  0.751 0.753 0.675  54 85 34  1 1.10 (0.75 - 1.63) 0.99 (0.61 - 1.61)  0.967 0.623 0.959  17 32 18  1 1.42 (0.75 - 2.66) 1.69 (0.83 - 3.46)  0.144 0.279 0.150  1 0.75 (0.51 - 1.09) 0.96 (0.55 - 1.68)  0.419 0.130 0.877  77 79 17  1 1.15 (0.80 - 1.66) 0.82 (0.45 - 1.47)  0.866 0.453 0.498  27 29 9  1 1.19 (0.68 - 2.11) 1.14 (0.51 - 2.58)  0.625 0.542 0.752  1 1.04 (0.62 - 1.73) 1.01 (0.60 - 1.68)  0.891 0.978  148 1 24 1.03 (0.63 - 1.70) 1 25 1.03 (0.623- 1.68)  0.908 -0.915  62 6 0 6  1 0.62 (0.26 - 1.49) 0.59 (0.25 - 1.43)  0.284 0.244  1 0.89 (0.51 - 1.57) 0.84 (0.48 - 1.47)  0.689 0.534  156 17 1 18  0.702 0.722  62 5 0 5  1 0.71 (0.27 - 1.84) 0.67 (0.26 - 1.75)  0.474 0.418  1 0.90 (0.51 - 1.58) 0.90 (0.52 - 1.58)  !"# #  SNP BLM_IVS12(+7)T/C T/T T/C C/C BLM_IVS21(60)_del(GAA) GAA/GAA GAA/-/-  Controls N N  DLBCL OR (95% CI)  p value  N  FL OR (95% CI)  p value  N  MZ/MALT OR (95% CI)  p value  316 88 243 58 45 15  1 0.85 (0.58 - 1.23) 1.23 (0.55 - 2.32)  0.944 0.389 0.533  88 68 16  1 0.99 (0.69 - 1.43) 1.21 (0.65 - 2.26)  0.696 0.975 0.554  33 29 5  1 1.18 (0.69 - 2.02) 1.12 (0.41 - 3.07)  0.609 0.546 0.823  237 61 283 81 76 19  1 1.09 (0.75 - 1.60) 0.94 (0.53 - 1.69)  0.968 0.640 0.840  74 75 24  1 0.87 (0.60 - 1.26) 0.98 (0.58 - 1.68)  0.727 0.452 0.949  37 21 8  1 0.46(0.26 - 0.82) 0.56 (0.24 - 1.27)  0.026 0.008 0.162  OR = Odds Ratio, CI = Confidence Interval, DLBCL = Diffuse Large B-Cell Lymphoma, FL = Follicular Lymphoma, MZ/MALT = Marginal Zone lymphoma/Mucosa-Associated Lymphoma Tissue lymphoma. If less than 5 samples were in a category, the analysis is not valid and marked by "-". Analyses were not done for subtypes that had fewer than 5 heterozygotes and minor homozygotes combined. Analysis is adjusted for adjusted for gender, ethnicity, age, and residence. p-value for test for trend is shown in italic type. p-values less than 0.05 are in bold. All results, including the results in Table 2.3, are in Appendices A.9a-d  !"# #  &J9K?76'[M'!7>7?A:'(96A9?A=>'A>'&7<<'279?J'!7>7@' 9>F'*A@H'=8'>=>50=FBHA>',DEKJ=E9∗' ;%%*!-%(0*%D!%E!-/DD!F/'0&!+(!D#SR&%-#0/G!-'(!D/'F!0%!'.0%+SS.(/!F+G/'G/!%*!-'(-/*Q! S'X+(L!L/(/G!+(K%DK/F!+(!R*%L*'SS/F!-/DD!F/'0&!%E!D#SR&%-#0/G!D%L+-'D!-'(F+F'0/! L/(/G!E%*!D#SR&%S'!G.G-/R0+"+D+0#V! 6!-'**+/F!%.0!0/G0G!E%*!L/(/0+-!'GG%-+'0+%(!\+0&!:4=!'(F!:4=!G."0#R/GQ!%E!,:;G!+(! 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