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000154601 1001_ $$aCampbell, Peter T$$b0
000154601 245__ $$aAssociation of body mass index with colorectal cancer risk by genome-wide variants.
000154601 260__ $$aOxford$$bOxford Univ. Press$$c2021
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000154601 500__ $$a2021 Jan 4;113(1):38-47
000154601 520__ $$aBody mass index (BMI) is a complex phenotype that may interact with genetic variants to influence colorectal cancer risk.We tested multiplicative statistical interactions between BMI (per 5 kg·m2) and approximately 2.7 million single nucleotide polymorphisms (SNPs) with colorectal cancer risk among 14,059 colorectal cancer case (53.2% women) and 14,416 control (53.8% women) participants. All analyses were stratified by sex a priori. Statistical methods included two-step (i.e., Cocktail method) and single-step (i.e., case-control logistic regression and a joint 2-degree of freedom test) procedures. All statistical tests were two-sided.Each 5 kg·m2 increase in BMI was associated with higher risks of colorectal cancer, less so for women (odds ratio [OR]: 1.14; 95% confidence intervals [CI]: 1.11-1.18; p-value: 9.75 x 10-17) than for men (OR: 1.26; 95% CI: 1.20-1.32; p-value: 2.13 x 10-24). The two-step Cocktail method identified an interaction for women, but not men, between BMI and a SMAD7 intronic variant at 18q21.1 (rs4939827; p-observed: 0.0009; p-threshold: 0.005). A joint 2-degree of freedom test was consistent with this finding for women (joint p-value: 2.43 x 10-10). Each 5 kg·m2 increase in BMI was more strongly associated with colorectal cancer risk for women with the rs4939827-CC genotype (OR: 1.24; 95% CI: 1.16-1.32; p-value: 2.60 x 10-10) than for women with the CT (OR: 1.14; 95% CI: 1.09-1.19; p-value: 1.04 x 10-8) or TT (OR: 1.07; 95% CI: 1.01-1.14; p-value: 0.02) genotypes.These results provide novel insights on a potential mechanism through which a SMAD7 variant, previously identified as a susceptibility locus for colorectal cancer, and BMI may influence colorectal cancer risk for women.
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000154601 7001_ $$aLin, Yi$$b1
000154601 7001_ $$aBien, Stephanie A$$b2
000154601 7001_ $$aFigueiredo, Jane C$$b3
000154601 7001_ $$aHarrison, Tabitha A$$b4
000154601 7001_ $$aGuinter, Mark J$$b5
000154601 7001_ $$aBerndt, Sonja I$$b6
000154601 7001_ $$0P:(DE-He78)90d5535ff896e70eed81f4a4f6f22ae2$$aBrenner, Hermann$$b7$$udkfz
000154601 7001_ $$aChan, Andrew T$$b8
000154601 7001_ $$0P:(DE-He78)c259d6cc99edf5c7bc7ce22c7f87c253$$aChang-Claude, Jenny$$b9$$udkfz
000154601 7001_ $$aGallinger, Steven J$$b10
000154601 7001_ $$aGapstur, Susan M$$b11
000154601 7001_ $$aGiles, Graham G$$b12
000154601 7001_ $$aGiovannucci, Edward$$b13
000154601 7001_ $$aGruber, Stephen B$$b14
000154601 7001_ $$aGunter, Marc$$b15
000154601 7001_ $$0P:(DE-He78)6c5d058b7552d071a7fa4c5e943fff0f$$aHoffmeister, Michael$$b16$$udkfz
000154601 7001_ $$aJacobs, Eric J$$b17
000154601 7001_ $$aJenkins, Mark A$$b18
000154601 7001_ $$aMarchand, Loic Le$$b19
000154601 7001_ $$aLi, Li$$b20
000154601 7001_ $$aMcLaughlin, John R$$b21
000154601 7001_ $$aMurphy, Neil$$b22
000154601 7001_ $$aMilne, Roger L$$b23
000154601 7001_ $$aNewcomb, Polly A$$b24
000154601 7001_ $$aNewton, Christina$$b25
000154601 7001_ $$aOgino, Shuji$$b26
000154601 7001_ $$aPotter, John D$$b27
000154601 7001_ $$aRennert, Gad$$b28
000154601 7001_ $$aRennert, Hedy S$$b29
000154601 7001_ $$aRobinson, Jennifer$$b30
000154601 7001_ $$aSakoda, Lori C$$b31
000154601 7001_ $$aSlattery, Martha L$$b32
000154601 7001_ $$aSong, Yiqing$$b33
000154601 7001_ $$aWhite, Emily$$b34
000154601 7001_ $$aWoods, Michael O$$b35
000154601 7001_ $$aCasey, Graham$$b36
000154601 7001_ $$aHsu, Li$$b37
000154601 7001_ $$aPeters, Ulrike$$b38
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