Mendelian randomization study of height and risk of colorectal cancer

Thrift, Aaron P, Gong, Jian, Peters, Ulrike, Chang-Claude, Jenny, Rudolph, Anja, Slattery, Martha L, Chan, Andrew T, Esko, Tonu, Wood, Andrew R, Yang, Jian, Vedantam, Sailaja, Gustafsson, Stefan, Pers, Tune H., Baron, John A., Bezieau, Stephane, Kuery, Sebastien, Ogino, Shuji, Berndt, Sonja I, Casey, Graham, Haile, Robert W, Du, Mengmeng, Harrison, Tabitha A, Thornquist, Mark, Duggan, David J., Le Marchand, Loic, Lemire, Mathieu, Lindor, Noralane M, Seminara, Daniela, Song, Mingyang, Thibodeau, Stephen N, Cotterchio, Michelle, Win, Aung Ko, Jenkins, Mark A, Hopper, John L, Ulrich, Cornelia M, Potter, John D, Newcomb, Polly A, Schoen, Robert E, Hoffmeister, Michael, Brenner, Hermann, White, Emily, Hsu, Li and Campbell, Peter T (2015) Mendelian randomization study of height and risk of colorectal cancer. International Journal of Epidemiology, 44 2: 662-672. doi:10.1093/ije/dyv082


Author Thrift, Aaron P
Gong, Jian
Peters, Ulrike
Chang-Claude, Jenny
Rudolph, Anja
Slattery, Martha L
Chan, Andrew T
Esko, Tonu
Wood, Andrew R
Yang, Jian
Vedantam, Sailaja
Gustafsson, Stefan
Pers, Tune H.
Baron, John A.
Bezieau, Stephane
Kuery, Sebastien
Ogino, Shuji
Berndt, Sonja I
Casey, Graham
Haile, Robert W
Du, Mengmeng
Harrison, Tabitha A
Thornquist, Mark
Duggan, David J.
Le Marchand, Loic
Lemire, Mathieu
Lindor, Noralane M
Seminara, Daniela
Song, Mingyang
Thibodeau, Stephen N
Cotterchio, Michelle
Win, Aung Ko
Jenkins, Mark A
Hopper, John L
Ulrich, Cornelia M
Potter, John D
Newcomb, Polly A
Schoen, Robert E
Hoffmeister, Michael
Brenner, Hermann
White, Emily
Hsu, Li
Campbell, Peter T
Title Mendelian randomization study of height and risk of colorectal cancer
Journal name International Journal of Epidemiology   Check publisher's open access policy
ISSN 1464-3685
0300-5771
Publication date 2015-05-20
Year available 2015
Sub-type Article (original research)
DOI 10.1093/ije/dyv082
Open Access Status Not yet assessed
Volume 44
Issue 2
Start page 662
End page 672
Total pages 11
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Language eng
Subject 2713 Epidemiology
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.
Formatted 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.
Keyword Body height
Colorectal cancer
Epidemiology
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID BR 1704/6-1
BR 1704/6-3
BR 1704/6-4
CH 117/1-1
HHSN 268201100046C
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NIH GEI U01 HG 004438
NIH U01 HG004446
P01 CA 055075
P01 CA 087969
P50 CA 127003
P50 CA 127003
R01 137178
R01 CA 151993
R01 CA042182
R01 CA059045
R01 CA059045
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R01 CA137178
R01 CA151993
R01 CA48998
RFA # CA-95-011
U01 CA122839
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U01 CA137088
U01 CA137088
U01 CA137088
UM1 CA167552
Z01 CP 010200
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2016 Collection
UQ Diamantina Institute Publications
 
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