Mendelian randomization study of height and risk of colorectal cancer

GIANT Consortium

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Background: For men and women, taller height is associated with increased risk of all cancers combined. For colorectal cancer (CRC), it is unclear whether the differential association of height by sex is real or is due to confounding or bias inherent in observational studies. We performed a Mendelian randomization study to examine the association between height and CRC risk. Methods: To minimize confounding and bias, we derived a weighted genetic risk score predicting height (using 696 genetic variants associated with height) in 10 226 CRC cases and 10 286 controls. Logistic regression was used to estimate odds ratios (OR) and 95%confidence intervals (95% CI) for associations between height, genetically predicted height and CRC. Results: Using conventional methods, increased height (per 10-cm increment) was associated with increased CRC risk (OR = 1.08, 95% CI = 1.02-1.15). In sex-specific analyses, height was associated with CRC risk for women (OR = 1.15, 95% CI = 1.05-1.26), but not men (OR = 0.98, 95% CI = 0.92-1.05). Consistent with these results, carrying greater numbers of (weighted) height-increasing alleles (per 1-unit increase) was associated with higher CRC risk for women and men combined (OR = 1.07, 95% CI = 1.01-1.14) and for women (OR = 1.09, 95% CI = 1.01-1.19). There was weaker evidence of an association for men (OR = 1.05, 95% CI = 0.96-1.15). Conclusion: We provide evidence for a causal association between height and CRC for women. The CRC-height association for men remains unclear and warrants further investigation in other large studies.

Original languageEnglish (US)
Article numberdyv082
Pages (from-to)662-672
Number of pages11
JournalInternational Journal of Epidemiology
Volume44
Issue number2
DOIs
StatePublished - May 27 2015

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Random Allocation
Colorectal Neoplasms
Odds Ratio
Confidence Intervals
Observational Studies
Logistic Models
Alleles

Keywords

  • Body height
  • Colorectal cancer
  • Epidemiology

ASJC Scopus subject areas

  • Epidemiology

Cite this

Mendelian randomization study of height and risk of colorectal cancer. / GIANT Consortium.

In: International Journal of Epidemiology, Vol. 44, No. 2, dyv082, 27.05.2015, p. 662-672.

Research output: Contribution to journalArticle

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title = "Mendelian randomization study of height and risk of colorectal cancer",
abstract = "Background: For men and women, taller height is associated with increased risk of all cancers combined. For colorectal cancer (CRC), it is unclear whether the differential association of height by sex is real or is due to confounding or bias inherent in observational studies. We performed a Mendelian randomization study to examine the association between height and CRC risk. Methods: To minimize confounding and bias, we derived a weighted genetic risk score predicting height (using 696 genetic variants associated with height) in 10 226 CRC cases and 10 286 controls. Logistic regression was used to estimate odds ratios (OR) and 95{\%}confidence intervals (95{\%} CI) for associations between height, genetically predicted height and CRC. Results: Using conventional methods, increased height (per 10-cm increment) was associated with increased CRC risk (OR = 1.08, 95{\%} CI = 1.02-1.15). In sex-specific analyses, height was associated with CRC risk for women (OR = 1.15, 95{\%} CI = 1.05-1.26), but not men (OR = 0.98, 95{\%} CI = 0.92-1.05). Consistent with these results, carrying greater numbers of (weighted) height-increasing alleles (per 1-unit increase) was associated with higher CRC risk for women and men combined (OR = 1.07, 95{\%} CI = 1.01-1.14) and for women (OR = 1.09, 95{\%} CI = 1.01-1.19). There was weaker evidence of an association for men (OR = 1.05, 95{\%} CI = 0.96-1.15). Conclusion: We provide evidence for a causal association between height and CRC for women. The CRC-height association for men remains unclear and warrants further investigation in other large studies.",
keywords = "Body height, Colorectal cancer, Epidemiology",
author = "{GIANT Consortium} and 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 Tonu Esko and Wood, {Andrew R.} and Jian Yang and Sailaja Vedantam and Stefan Gustafsson and Pers, {Tune H.} and Baron, {John A.} and St{\'e}phane Bezieau and S{\'e}bastien K{\"u}ry and Shuji Ogino and Berndt, {Sonja I.} and Graham Casey and Haile, {Robert W.} and Mengmeng Du and Harrison, {Tabitha A.} and Mark Thornquist and Duggan, {David J.} and {Le Marchand}, Loic and Mathieu Lemire and Lindor, {Noralane Morey} and Daniela Seminara and Mingyang Song and Thibodeau, {Stephen N} and Michelle Cotterchio and Win, {Aung Ko} and Jenkins, {Mark A.} and Hopper, {John L.} and Ulrich, {Cornelia M.} and Potter, {John D.} and Newcomb, {Polly A.} and Schoen, {Robert E.} 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 height and risk of colorectal cancer

AU - GIANT Consortium

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 - Esko, Tonu

AU - Wood, Andrew R.

AU - Yang, Jian

AU - Vedantam, Sailaja

AU - Gustafsson, Stefan

AU - Pers, Tune H.

AU - Baron, John A.

AU - Bezieau, Stéphane

AU - Küry, Sébastien

AU - Ogino, Shuji

AU - Berndt, Sonja I.

AU - Casey, Graham

AU - Haile, Robert W.

AU - Du, Mengmeng

AU - Harrison, Tabitha A.

AU - Thornquist, Mark

AU - Duggan, David J.

AU - Le Marchand, Loic

AU - Lemire, Mathieu

AU - Lindor, Noralane Morey

AU - Seminara, Daniela

AU - Song, Mingyang

AU - Thibodeau, Stephen N

AU - Cotterchio, Michelle

AU - Win, Aung Ko

AU - Jenkins, Mark A.

AU - Hopper, John L.

AU - Ulrich, Cornelia M.

AU - Potter, John D.

AU - Newcomb, Polly A.

AU - Schoen, Robert E.

AU - Hoffmeister, Michael

AU - Brenner, Hermann

AU - White, Emily

AU - Hsu, Li

AU - Campbell, Peter T.

PY - 2015/5/27

Y1 - 2015/5/27

N2 - Background: For men and women, taller height is associated with increased risk of all cancers combined. For colorectal cancer (CRC), it is unclear whether the differential association of height by sex is real or is due to confounding or bias inherent in observational studies. We performed a Mendelian randomization study to examine the association between height and CRC risk. Methods: To minimize confounding and bias, we derived a weighted genetic risk score predicting height (using 696 genetic variants associated with height) in 10 226 CRC cases and 10 286 controls. Logistic regression was used to estimate odds ratios (OR) and 95%confidence intervals (95% CI) for associations between height, genetically predicted height and CRC. Results: Using conventional methods, increased height (per 10-cm increment) was associated with increased CRC risk (OR = 1.08, 95% CI = 1.02-1.15). In sex-specific analyses, height was associated with CRC risk for women (OR = 1.15, 95% CI = 1.05-1.26), but not men (OR = 0.98, 95% CI = 0.92-1.05). Consistent with these results, carrying greater numbers of (weighted) height-increasing alleles (per 1-unit increase) was associated with higher CRC risk for women and men combined (OR = 1.07, 95% CI = 1.01-1.14) and for women (OR = 1.09, 95% CI = 1.01-1.19). There was weaker evidence of an association for men (OR = 1.05, 95% CI = 0.96-1.15). Conclusion: We provide evidence for a causal association between height and CRC for women. The CRC-height association for men remains unclear and warrants further investigation in other large studies.

AB - Background: For men and women, taller height is associated with increased risk of all cancers combined. For colorectal cancer (CRC), it is unclear whether the differential association of height by sex is real or is due to confounding or bias inherent in observational studies. We performed a Mendelian randomization study to examine the association between height and CRC risk. Methods: To minimize confounding and bias, we derived a weighted genetic risk score predicting height (using 696 genetic variants associated with height) in 10 226 CRC cases and 10 286 controls. Logistic regression was used to estimate odds ratios (OR) and 95%confidence intervals (95% CI) for associations between height, genetically predicted height and CRC. Results: Using conventional methods, increased height (per 10-cm increment) was associated with increased CRC risk (OR = 1.08, 95% CI = 1.02-1.15). In sex-specific analyses, height was associated with CRC risk for women (OR = 1.15, 95% CI = 1.05-1.26), but not men (OR = 0.98, 95% CI = 0.92-1.05). Consistent with these results, carrying greater numbers of (weighted) height-increasing alleles (per 1-unit increase) was associated with higher CRC risk for women and men combined (OR = 1.07, 95% CI = 1.01-1.14) and for women (OR = 1.09, 95% CI = 1.01-1.19). There was weaker evidence of an association for men (OR = 1.05, 95% CI = 0.96-1.15). Conclusion: We provide evidence for a causal association between height and CRC for women. The CRC-height association for men remains unclear and warrants further investigation in other large studies.

KW - Body height

KW - Colorectal cancer

KW - Epidemiology

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U2 - 10.1093/ije/dyv082

DO - 10.1093/ije/dyv082

M3 - Article

C2 - 25997436

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VL - 44

SP - 662

EP - 672

JO - International Journal of Epidemiology

JF - International Journal of Epidemiology

SN - 0300-5771

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ER -