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Genome-Wide Diet-Gene Interaction Analyses for Risk of Colorectal Cancer

Figueiredo, JC and Hsu, L and Hutter, CM and Lin, Y and Campbell, PT and Baron, JA and Berndt, SI and Jiao, S and Casey, G and Fortini, B and Chan, AT and Cotterchio, M and Lemire, M and Gallinger, S and Harrison, TA and Le Marchand, L and Newcomb, PA and Slattery, ML and Caan, BJ and Carlson, CS and Zanke, BW and Rosse, SA and Brenner, H and Giovannucci, EL and Wu, K and Chang-Claude, J and Chanock, SJ and Curtis, KR and Duggan, D and Gong, J and Haile, RW and Hayes, RB and Hoffmeister, M and Hopper, JL and Jenkins, MA and Kolonel, LN and Qu, C and Rudolph, A and Schoen, RE and Schumacher, FR and Seminara, D and Stelling, DL and Thibodeau, SN and Thornquist, M and Warnick, GS and Henderson, BE and Ulrich, CM and Gauderman, WJ and Potter, JD and White, E and Peters, U (2014) Genome-Wide Diet-Gene Interaction Analyses for Risk of Colorectal Cancer. PLoS Genetics, 10 (4). ISSN 1553-7390

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Dietary factors, including meat, fruits, vegetables and fiber, are associated with colorectal cancer; however, there is limited information as to whether these dietary factors interact with genetic variants to modify risk of colorectal cancer. We tested interactions between these dietary factors and approximately 2.7 million genetic variants for colorectal cancer risk among 9,287 cases and 9,117 controls from ten studies. We used logistic regression to investigate multiplicative gene-diet interactions, as well as our recently developed Cocktail method that involves a screening step based on marginal associations and gene-diet correlations and a testing step for multiplicative interactions, while correcting for multiple testing using weighted hypothesis testing. Per quartile increment in the intake of red and processed meat were associated with statistically significant increased risks of colorectal cancer and vegetable, fruit and fiber intake with lower risks. From the case-control analysis, we detected a significant interaction between rs4143094 (10p14/near GATA3) and processed meat consumption (OR = 1.17; p = 8.7E-09), which was consistently observed across studies (p heterogeneity = 0.78). The risk of colorectal cancer associated with processed meat was increased among individuals with the rs4143094-TG and -TT genotypes (OR = 1.20 and OR = 1.39, respectively) and null among those with the GG genotype (OR = 1.03). Our results identify a novel gene-diet interaction with processed meat for colorectal cancer, highlighting that diet may modify the effect of genetic variants on disease risk, which may have important implications for prevention. © 2014.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Figueiredo, JC
Hsu, L
Hutter, CM
Lin, Y
Campbell, PT
Baron, JA
Berndt, SI
Jiao, S
Casey, G
Fortini, B
Chan, AT
Cotterchio, M
Lemire, M
Gallinger, S
Harrison, TA
Le Marchand, L
Newcomb, PA
Slattery, ML
Caan, BJ
Carlson, CS
Zanke, BW
Rosse, SA
Brenner, H
Giovannucci, EL
Wu, K
Chang-Claude, J
Chanock, SJ
Curtis, KR
Duggan, D
Gong, J
Haile, RW
Hayes, RB
Hoffmeister, M
Hopper, JL
Jenkins, MA
Kolonel, LN
Qu, C
Rudolph, A
Schoen, RErschoen@pitt.eduRSCHOEN0000-0001-7153-2766
Schumacher, FR
Seminara, D
Stelling, DL
Thibodeau, SN
Thornquist, M
Warnick, GS
Henderson, BE
Ulrich, CM
Gauderman, WJ
Potter, JD
White, E
Peters, U
ContributionContributors NameEmailPitt UsernameORCID
Date: 1 January 2014
Date Type: Publication
Journal or Publication Title: PLoS Genetics
Volume: 10
Number: 4
DOI or Unique Handle: 10.1371/journal.pgen.1004228
Schools and Programs: School of Public Health > Epidemiology
School of Medicine > Medicine
Refereed: Yes
ISSN: 1553-7390
Date Deposited: 25 Jun 2014 22:42
Last Modified: 02 Feb 2019 16:58


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