Mendelian randomization study of body mass index and colorectal cancer risk

Aaron P. Thrift, Jian Gong, Ulrike Peters, Jenny Chang-Claude, Anja Rudolph, Martha L. Slattery, Andrew T. Chan, Adam E. Locke, Bratati Kahali, Anne E. Justice, Tune H. Pers, Steven Gallinger, Richard B. Hayes, John A. Baron, Bette J.caan, Shuji Ogino, Sonja I. Berndt, Stephen J. Chanock, Graham Casey, Robert W. Haile & 22 others Mengmeng Du, Tabitha A. Harrison, Mark Thornquist, David J. Duggan, Loïc Le Marchand, Noralane M. Lindor, Daniela Seminara, Mingyang Song, Kana Wu, Stephen N. Thibodeau, Michelle Cotterchio, Aung Ko Win, Mark A. Jenkins, John Hopper, Cornelia M. Ulrich, John D. Potter, Polly A. Newcomb, Michael Hoffmeister, Hermann Brenner, Emily White, Li Hsu, Peter T. Campbell

Research output: Contribution to journalArticle

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:Weused 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/m2, 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/m2, 1.82; 95% CI, 1.26-2.61). For men, genetically influenced BMI was not associated with colorectal cancer (IV-OR per 5 kg/m2, 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.

Original languageEnglish (US)
Pages (from-to)1024-1031
Number of pages8
JournalCancer Epidemiology Biomarkers and Prevention
Volume24
Issue number7
DOIs
StatePublished - Jul 1 2015
Externally publishedYes

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Random Allocation
Colorectal Neoplasms
Body Mass Index
Confidence Intervals
Mendelian Randomization Analysis
Obesity
Alleles
Abdominal Obesity
Genome-Wide Association Study
Observational Studies
Odds Ratio

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Thrift, A. P., Gong, J., Peters, U., Chang-Claude, J., Rudolph, A., Slattery, M. L., ... Campbell, P. T. (2015). Mendelian randomization study of body mass index and colorectal cancer risk. Cancer Epidemiology Biomarkers and Prevention, 24(7), 1024-1031. https://doi.org/10.1158/1055-9965.EPI-14-1309

Mendelian randomization study of body mass index and colorectal cancer risk. / Thrift, Aaron P.; Gong, Jian; Peters, Ulrike; Chang-Claude, Jenny; Rudolph, Anja; Slattery, Martha L.; Chan, Andrew T.; Locke, Adam E.; Kahali, Bratati; Justice, Anne E.; Pers, Tune H.; Gallinger, Steven; Hayes, Richard B.; Baron, John A.; J.caan, Bette; Ogino, Shuji; Berndt, Sonja I.; Chanock, Stephen J.; Casey, Graham; Haile, Robert W.; Du, Mengmeng; Harrison, Tabitha A.; Thornquist, Mark; Duggan, David J.; Le Marchand, Loïc; Lindor, Noralane M.; Seminara, Daniela; Song, Mingyang; Wu, Kana; Thibodeau, Stephen N.; Cotterchio, Michelle; Win, Aung Ko; Jenkins, Mark A.; Hopper, John; Ulrich, Cornelia M.; Potter, John D.; Newcomb, Polly A.; Hoffmeister, Michael; Brenner, Hermann; White, Emily; Hsu, Li; Campbell, Peter T.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 24, No. 7, 01.07.2015, p. 1024-1031.

Research output: Contribution to journalArticle

Thrift, AP, Gong, J, Peters, U, Chang-Claude, J, Rudolph, A, Slattery, ML, Chan, AT, Locke, AE, Kahali, B, Justice, AE, Pers, TH, Gallinger, S, Hayes, RB, Baron, JA, J.caan, B, Ogino, S, Berndt, SI, Chanock, SJ, Casey, G, Haile, RW, Du, M, Harrison, TA, Thornquist, M, Duggan, DJ, Le Marchand, L, Lindor, NM, Seminara, D, Song, M, Wu, K, Thibodeau, SN, Cotterchio, M, Win, AK, Jenkins, MA, Hopper, J, Ulrich, CM, Potter, JD, Newcomb, PA, Hoffmeister, M, Brenner, H, White, E, Hsu, L & Campbell, PT 2015, 'Mendelian randomization study of body mass index and colorectal cancer risk', Cancer Epidemiology Biomarkers and Prevention, vol. 24, no. 7, pp. 1024-1031. https://doi.org/10.1158/1055-9965.EPI-14-1309
Thrift, Aaron P. ; Gong, Jian ; Peters, Ulrike ; Chang-Claude, Jenny ; Rudolph, Anja ; Slattery, Martha L. ; Chan, Andrew T. ; Locke, Adam E. ; Kahali, Bratati ; Justice, Anne E. ; Pers, Tune H. ; Gallinger, Steven ; Hayes, Richard B. ; Baron, John A. ; J.caan, Bette ; Ogino, Shuji ; Berndt, Sonja I. ; Chanock, Stephen J. ; Casey, Graham ; Haile, Robert W. ; Du, Mengmeng ; Harrison, Tabitha A. ; Thornquist, Mark ; Duggan, David J. ; Le Marchand, Loïc ; Lindor, Noralane M. ; Seminara, Daniela ; Song, Mingyang ; Wu, Kana ; Thibodeau, Stephen N. ; Cotterchio, Michelle ; Win, Aung Ko ; Jenkins, Mark A. ; Hopper, John ; Ulrich, Cornelia M. ; Potter, John D. ; Newcomb, Polly A. ; Hoffmeister, Michael ; Brenner, Hermann ; White, Emily ; Hsu, Li ; Campbell, Peter T. / Mendelian randomization study of body mass index and colorectal cancer risk. In: Cancer Epidemiology Biomarkers and Prevention. 2015 ; Vol. 24, No. 7. pp. 1024-1031.
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title = "Mendelian randomization study of body mass index and colorectal cancer risk",
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:Weused 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/m2, 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/m2, 1.82; 95{\%} CI, 1.26-2.61). For men, genetically influenced BMI was not associated with colorectal cancer (IV-OR per 5 kg/m2, 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.",
author = "Thrift, {Aaron P.} and Jian Gong and Ulrike Peters and Jenny Chang-Claude and Anja Rudolph and Slattery, {Martha L.} and Chan, {Andrew T.} and Locke, {Adam E.} and Bratati Kahali and Justice, {Anne E.} and Pers, {Tune H.} and Steven Gallinger and Hayes, {Richard B.} and Baron, {John A.} and Bette J.caan and Shuji Ogino and Berndt, {Sonja I.} and Chanock, {Stephen J.} and Graham Casey and Haile, {Robert W.} and Mengmeng Du and Harrison, {Tabitha A.} and Mark Thornquist and Duggan, {David J.} and {Le Marchand}, Lo{\"i}c and Lindor, {Noralane M.} and Daniela Seminara and Mingyang Song and Kana Wu and Thibodeau, {Stephen N.} and Michelle Cotterchio and Win, {Aung Ko} and Jenkins, {Mark A.} and John Hopper and Ulrich, {Cornelia M.} and Potter, {John D.} and Newcomb, {Polly A.} and Michael Hoffmeister and Hermann Brenner and Emily White and Li Hsu and Campbell, {Peter T.}",
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T1 - Mendelian randomization study of body mass index and colorectal cancer risk

AU - Thrift, Aaron P.

AU - Gong, Jian

AU - Peters, Ulrike

AU - Chang-Claude, Jenny

AU - Rudolph, Anja

AU - Slattery, Martha L.

AU - Chan, Andrew T.

AU - Locke, Adam E.

AU - Kahali, Bratati

AU - Justice, Anne E.

AU - Pers, Tune H.

AU - Gallinger, Steven

AU - Hayes, Richard B.

AU - Baron, John A.

AU - J.caan, Bette

AU - Ogino, Shuji

AU - Berndt, Sonja I.

AU - Chanock, Stephen J.

AU - Casey, Graham

AU - Haile, Robert W.

AU - Du, Mengmeng

AU - Harrison, Tabitha A.

AU - Thornquist, Mark

AU - Duggan, David J.

AU - Le Marchand, Loïc

AU - Lindor, Noralane M.

AU - Seminara, Daniela

AU - Song, Mingyang

AU - Wu, Kana

AU - Thibodeau, Stephen N.

AU - Cotterchio, Michelle

AU - Win, Aung Ko

AU - Jenkins, Mark A.

AU - Hopper, John

AU - Ulrich, Cornelia M.

AU - Potter, John D.

AU - Newcomb, Polly A.

AU - Hoffmeister, Michael

AU - Brenner, Hermann

AU - White, Emily

AU - Hsu, Li

AU - Campbell, Peter T.

PY - 2015/7/1

Y1 - 2015/7/1

N2 - 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:Weused 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/m2, 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/m2, 1.82; 95% CI, 1.26-2.61). For men, genetically influenced BMI was not associated with colorectal cancer (IV-OR per 5 kg/m2, 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.

AB - 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:Weused 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/m2, 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/m2, 1.82; 95% CI, 1.26-2.61). For men, genetically influenced BMI was not associated with colorectal cancer (IV-OR per 5 kg/m2, 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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