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Multicenter Study
. 2015 Jul;24(7):1024-31.
doi: 10.1158/1055-9965.EPI-14-1309. Epub 2015 May 14.

Mendelian Randomization Study of Body Mass Index and Colorectal Cancer Risk

Aaron P Thrift  1 , Jian Gong  2 , Ulrike Peters  3 , Jenny Chang-Claude  4 , Anja Rudolph  4 , Martha L Slattery  5 , Andrew T Chan  6 , Adam E Locke  7 , Bratati Kahali  8 , Anne E Justice  9 , Tune H Pers  10 , Steven Gallinger  11 , Richard B Hayes  12 , John A Baron  13 , Bette J Caan  14 , Shuji Ogino  15 , Sonja I Berndt  16 , Stephen J Chanock  16 , Graham Casey  17 , Robert W Haile  18 , Mengmeng Du  19 , Tabitha A Harrison  2 , Mark Thornquist  2 , David J Duggan  20 , Loïc Le Marchand  21 , Noralane M Lindor  22 , Daniela Seminara  23 , Mingyang Song  24 , Kana Wu  25 , Stephen N Thibodeau  26 , Michelle Cotterchio  27 , Aung Ko Win  28 , Mark A Jenkins  28 , John L Hopper  28 , Cornelia M Ulrich  29 , John D Potter  30 , Polly A Newcomb  3 , Michael Hoffmeister  31 , Hermann Brenner  32 , Emily White  3 , Li Hsu  33 , Peter T Campbell  34
Affiliations
Multicenter Study

Mendelian Randomization Study of Body Mass Index and Colorectal Cancer Risk

Aaron P Thrift et al. Cancer Epidemiol Biomarkers Prev. 2015 Jul.

Abstract

Background: High body mass index (BMI) is consistently linked to increased risk of colorectal cancer for men, whereas the association is less clear for women. As risk estimates from observational studies may be biased and/or confounded, we conducted a Mendelian randomization study to estimate the causal association between BMI and colorectal cancer.

Methods: We used data from 10,226 colorectal cancer cases and 10,286 controls of European ancestry. The Mendelian randomization analysis used a weighted genetic risk score, derived from 77 genome-wide association study-identified variants associated with higher BMI, as an instrumental variable (IV). We compared the IV odds ratio (IV-OR) with the OR obtained using a conventional covariate-adjusted analysis.

Results: Individuals carrying greater numbers of BMI-increasing alleles had higher colorectal cancer risk [per weighted allele OR, 1.31; 95% confidence interval (CI), 1.10-1.57]. Our IV estimation results support the hypothesis that genetically influenced BMI is directly associated with risk for colorectal cancer (IV-OR per 5 kg/m(2), 1.50; 95% CI, 1.13-2.01). In the sex-specific IV analyses higher BMI was associated with higher risk of colorectal cancer among women (IV-OR per 5 kg/m(2), 1.82; 95% CI, 1.26-2.61). For men, genetically influenced BMI was not associated with colorectal cancer (IV-OR per 5 kg/m(2), 1.18; 95% CI, 0.73-1.92).

Conclusions: High BMI was associated with increased colorectal cancer risk for women. Whether abdominal obesity, rather than overall obesity, is a more important risk factor for men requires further investigation.

Impact: Overall, conventional epidemiologic and Mendelian randomization studies suggest a strong association between obesity and the risk of colorectal cancer.

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Conflict of interest statement

Disclosure of potential conflicts of interest: No potential conflicts of interest to disclose.

Figures

Figure 1
Figure 1
The association between the weighted genetic risk score (the instrumental variable) and body mass index (BMI) across the 11 participating studies in GECCO and C-CFR.
See this image and copyright information in PMC

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