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@ARTICLE{Campbell:154601,
author = {P. T. Campbell and Y. Lin and S. A. Bien and J. C.
Figueiredo and T. A. Harrison and M. J. Guinter and S. I.
Berndt and H. Brenner$^*$ and A. T. Chan and J.
Chang-Claude$^*$ and S. J. Gallinger and S. M. Gapstur and
G. G. Giles and E. Giovannucci and S. B. Gruber and M.
Gunter and M. Hoffmeister$^*$ and E. J. Jacobs and M. A.
Jenkins and L. L. Marchand and L. Li and J. R. McLaughlin
and N. Murphy and R. L. Milne and P. A. Newcomb and C.
Newton and S. Ogino and J. D. Potter and G. Rennert and H.
S. Rennert and J. Robinson and L. C. Sakoda and M. L.
Slattery and Y. Song and E. White and M. O. Woods and G.
Casey and L. Hsu and U. Peters},
title = {{A}ssociation of body mass index with colorectal cancer
risk by genome-wide variants.},
journal = {Journal of the National Cancer Institute},
volume = {113},
number = {1},
issn = {1460-2105},
address = {Oxford},
publisher = {Oxford Univ. Press},
reportid = {DKFZ-2020-00874},
pages = {38-47},
year = {2021},
note = {2021 Jan 4;113(1):38-47},
abstract = {Body mass index (BMI) is a complex phenotype that may
interact with genetic variants to influence colorectal
cancer risk.We tested multiplicative statistical
interactions between BMI (per 5 kg·m2) and approximately
2.7 million single nucleotide polymorphisms (SNPs) with
colorectal cancer risk among 14,059 colorectal cancer case
$(53.2\%$ women) and 14,416 control $(53.8\%$ women)
participants. All analyses were stratified by sex a priori.
Statistical methods included two-step (i.e., Cocktail
method) and single-step (i.e., case-control logistic
regression and a joint 2-degree of freedom test) procedures.
All statistical tests were two-sided.Each 5 kg·m2
increase in BMI was associated with higher risks of
colorectal cancer, less so for women (odds ratio [OR]: 1.14;
$95\%$ confidence intervals [CI]: 1.11-1.18; p-value: 9.75 x
10-17) than for men (OR: 1.26; $95\%$ CI: 1.20-1.32;
p-value: 2.13 x 10-24). The two-step Cocktail method
identified an interaction for women, but not men, between
BMI and a SMAD7 intronic variant at 18q21.1 (rs4939827;
p-observed: 0.0009; p-threshold: 0.005). A joint 2-degree of
freedom test was consistent with this finding for women
(joint p-value: 2.43 x 10-10). Each 5 kg·m2 increase in
BMI was more strongly associated with colorectal cancer risk
for women with the rs4939827-CC genotype (OR: 1.24; $95\%$
CI: 1.16-1.32; p-value: 2.60 x 10-10) than for women with
the CT (OR: 1.14; $95\%$ CI: 1.09-1.19; p-value: 1.04 x
10-8) or TT (OR: 1.07; $95\%$ CI: 1.01-1.14; p-value: 0.02)
genotypes.These results provide novel insights on a
potential mechanism through which a SMAD7 variant,
previously identified as a susceptibility locus for
colorectal cancer, and BMI may influence colorectal cancer
risk for women.},
cin = {C070 / C120 / HD01 / C020},
ddc = {610},
cid = {I:(DE-He78)C070-20160331 / I:(DE-He78)C120-20160331 /
I:(DE-He78)HD01-20160331 / I:(DE-He78)C020-20160331},
pnm = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
pid = {G:(DE-HGF)POF4-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:32324875},
doi = {10.1093/jnci/djaa058},
url = {https://inrepo02.dkfz.de/record/154601},
}