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 Hannes Pers

    Research output: Contribution to journalJournal articleResearchpeer-review

    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/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
    JournalCancer Epidemiology, Biomarkers & Prevention
    Volume24
    Issue number7
    Pages (from-to)1024-1031
    Number of pages8
    ISSN1055-9965
    DOIs
    Publication statusPublished - 2015

    Cite this

    Thrift, A. P., Gong, J., Peters, U., Chang-Claude, J., Rudolph, A., Slattery, M. L., ... Pers, T. H. (2015). Mendelian Randomization Study of Body Mass Index and Colorectal Cancer Risk. Cancer Epidemiology, Biomarkers & Prevention, 24(7), 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 Hannes. / Mendelian Randomization Study of Body Mass Index and Colorectal Cancer Risk. In: Cancer Epidemiology, Biomarkers & Prevention. 2015 ; Vol. 24, No. 7. pp. 1024-1031.
    @article{212a78708cd747dd9bb3d8c6ad3811b3,
    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: 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/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 Hannes}",
    year = "2015",
    doi = "10.1158/1055-9965.EPI-14-1309",
    language = "English",
    volume = "24",
    pages = "1024--1031",
    journal = "Cancer Epidemiology, Biomarkers & Prevention",
    issn = "1055-9965",
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    number = "7",

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    Thrift, AP, Gong, J, Peters, U, Chang-Claude, J, Rudolph, A, Slattery, ML, Chan, AT, Locke, AE, Kahali, B, Justice, AE & Pers, TH 2015, 'Mendelian Randomization Study of Body Mass Index and Colorectal Cancer Risk', Cancer Epidemiology, Biomarkers & Prevention, vol. 24, no. 7, pp. 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 Hannes.

    In: Cancer Epidemiology, Biomarkers & Prevention, Vol. 24, No. 7, 2015, p. 1024-1031.

    Research output: Contribution to journalJournal articleResearchpeer-review

    TY - JOUR

    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 Hannes

    PY - 2015

    Y1 - 2015

    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: 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/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: 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/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.

    U2 - 10.1158/1055-9965.EPI-14-1309

    DO - 10.1158/1055-9965.EPI-14-1309

    M3 - Journal article

    VL - 24

    SP - 1024

    EP - 1031

    JO - Cancer Epidemiology, Biomarkers & Prevention

    JF - Cancer Epidemiology, Biomarkers & Prevention

    SN - 1055-9965

    IS - 7

    ER -