Journal Article

DKFZ-2020-00874

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Association of body mass index with colorectal cancer risk by genome-wide variants.

Campbell, P. T. ; Lin, Y. ; Bien, S. A. ; Figueiredo, J. C. ; Harrison, T. A. ; Guinter, M. J. ; Berndt, S. I. ; Brenner, H.DKFZ* ; Chan, A. T. ; Chang-Claude, J.DKFZ* ; Gallinger, S. J. ; Gapstur, S. M. ; Giles, G. G. ; Giovannucci, E. ; Gruber, S. B. ; Gunter, M. ; Hoffmeister, M.DKFZ* ; Jacobs, E. J. ; Jenkins, M. A. ; Marchand, L. L. ; Li, L. ; McLaughlin, J. R. ; Murphy, N. ; Milne, R. L. ; Newcomb, P. A. ; Newton, C. ; Ogino, S. ; Potter, J. D. ; Rennert, G. ; Rennert, H. S. ; Robinson, J. ; Sakoda, L. C. ; Slattery, M. L. ; Song, Y. ; White, E. ; Woods, M. O. ; Casey, G. ; Hsu, L. ; Peters, U.

2021
Oxford Univ. Press Oxford

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Please use a persistent id in citations: doi:10.1093/jnci/djaa058

Abstract: Body 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.

Note: 2021 Jan 4;113(1):38-47

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Contributing Institute(s):

1. C070 Klinische Epidemiologie und Alternf. (C070)
2. Präventive Onkologie (C120)
3. DKTK HD zentral (HD01)
4. C020 Epidemiologie von Krebs (C020)

Research Program(s):

1. 313 - Krebsrisikofaktoren und Prävention (POF4-313) (POF4-313)

Appears in the scientific report 2021

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 10 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; PubMed Central ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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