Association of Body Mass Index With Colorectal Cancer Risk by Genome-Wide Variants

Peter T Campbell; Yi Lin; Stephanie A Bien; Jane C Figueiredo; Tabitha A Harrison; Mark A Guinter; Sonja I Berndt; Hermann Brenner; Andrew T Chan; Jenny Chang-Claude; Steven J Gallinger; Susan M Gapstur; Graham G Giles; Edward Giovannucci; Stephen B Gruber; Marc Gunter; Michael Hoffmeister; Eric J Jacobs; Mark A Jenkins; Loic Le Marchand; Li Li; John R McLaughlin; Neil Murphy; Roger L Milne; Polly A Newcomb; Christina Newton; Shuji Ogino; John D Potter; Gad Rennert; Hedy S Rennert; Jennifer Robinson; Lori C Sakoda; Martha L Slattery; Yiqing Song; Emily White; Michael O Woods; Graham Casey; Li Hsu; Ulrike Peters

doi:10.1093/jnci/djaa058

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Association of Body Mass Index With Colorectal Cancer Risk by Genome-Wide Variants

Journal article

Open access

Peer reviewed

Association of Body Mass Index With Colorectal Cancer Risk by Genome-Wide Variants

Peter T Campbell, Yi Lin, Stephanie A Bien, Jane C Figueiredo, Tabitha A Harrison, Mark A Guinter, Sonja I Berndt, Hermann Brenner, Andrew T Chan, Jenny Chang-Claude, …

JNCI : Journal of the National Cancer Institute, Vol.113(1), pp.38-47

01/04/2021

DOI: 10.1093/jnci/djaa058

PMCID: PMC7781451

PMID: 32324875

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781451View

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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 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 2-step (ie, Cocktail method) and single-step (ie, 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 to 1.18; P = 9.75 × 10-17) than for men (OR = 1.26, 95% CI = 1.20 to 1.32; P = 2.13 × 10-24). The 2-step Cocktail method identified an interaction for women, but not men, between BMI and a SMAD7 intronic variant at 18q21.1 (rs4939827; Pobserved = .0009; Pthreshold = .005). A joint 2-degree of freedom test was consistent with this finding for women (joint P = 2.43 × 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 to 1.32; P = 2.60 × 10-10) than for women with the CT (OR = 1.14, 95% CI = 1.09 to 1.19; P = 1.04 × 10-8) or TT (OR = 1.07, 95% CI = 1.01 to 1.14; P = .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.

Aged

Body Mass Index

Colorectal Neoplasms - epidemiology

Colorectal Neoplasms - genetics

Colorectal Neoplasms - pathology

Female

Genetic Predisposition to Disease

Genome-Wide Association Study

Genotype

Humans

Logistic Models

Male

Middle Aged

Polymorphism, Single Nucleotide - genetics

Risk Assessment

Risk Factors

Smad7 Protein - genetics

Details

Title: Subtitle: Association of Body Mass Index With Colorectal Cancer Risk by Genome-Wide Variants
Creators: Peter T Campbell - Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, GA, USA
Yi Lin - Fred Hutch Cancer Center
Stephanie A Bien - Fred Hutch Cancer Center
Jane C Figueiredo - Cedars-Sinai Medical Center
Tabitha A Harrison - Fred Hutch Cancer Center
Mark A Guinter - American Cancer Society
Sonja I Berndt - National Institutes of Health
Hermann Brenner - German Cancer Research Center
Andrew T Chan - Massachusetts General Hospital
Jenny Chang-Claude - German Cancer Research Center
Steven J Gallinger - Lunenfeld-Tanenbaum Research Institute
Susan M Gapstur - American Cancer Society
Graham G Giles - Monash University
Edward Giovannucci - Harvard University
Stephen B Gruber - City Of Hope National Medical Center
Marc Gunter - Centre International de Recherche sur le Cancer
Michael Hoffmeister - German Cancer Research Center
Eric J Jacobs - American Cancer Society
Mark A Jenkins - University of Melbourne
Loic Le Marchand - University of Hawaii System
Li Li - University of Virginia
John R McLaughlin - University of Toronto
Neil Murphy - Centre International de Recherche sur le Cancer
Roger L Milne - Cancer Council Victoria
Polly A Newcomb - Fred Hutch Cancer Center
Christina Newton - American Cancer Society
Shuji Ogino - Broad Institute
John D Potter - Fred Hutch Cancer Center
Gad Rennert - Carmel Medical Center
Hedy S Rennert - Clalit National Cancer Control Center, Haifa, Israel
Jennifer Robinson - University of Iowa
Lori C Sakoda - Kaiser Permanente
Martha L Slattery - University of Utah
Yiqing Song - Indiana University – Purdue University Indianapolis
Emily White - Fred Hutch Cancer Center
Michael O Woods - Memorial University of Newfoundland
Graham Casey - University of Virginia
Li Hsu - Fred Hutch Cancer Center
Ulrike Peters - University of Washington
Resource Type: Journal article
Publication Details: JNCI : Journal of the National Cancer Institute, Vol.113(1), pp.38-47
DOI: 10.1093/jnci/djaa058
PMID: 32324875
PMCID: PMC7781451
ISSN: 0027-8874
eISSN: 1460-2105
Grant note: R01 CA063464 / NCI NIH HHS P30 CA015704 / NCI NIH HHS R01 CA059045 / NCI NIH HHS U01 CA137088 / NCI NIH HHS U01 CA167551 / NCI NIH HHS R37 CA054281 / NCI NIH HHS U01 CA206110 / NCI NIH HHS R01 CA201407 / NCI NIH HHS K05 CA154337 / NCI NIH HHS U19 CA148107 / NCI NIH HHS R01 CA048998 / NCI NIH HHS P01 CA033619 / NCI NIH HHS U01 CA164930 / NCI NIH HHS R01 CA197350 / NCI NIH HHS R01 CA081488 / NCI NIH HHS
Language: English
Date published: 01/04/2021
Academic Unit: Epidemiology; Fraternal Order of Eagles Diabetes Research Center
Record Identifier: 9984363586102771

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