Abstract | BACKGROUND: METHODS: We analyzed 6,246 CRC cases and 7,714 population-based controls from 11 studies within the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Associations of each variant with obesity or CRC were evaluated using multivariate logistic regression models stratified by sex and adjusted for age, a study variable, and the first three principal components of genetic ancestry. Gene-specific False Discovery Rate (FDR)-adjusted p-values <0.05 denoted statistical significance. RESULTS: Two variants in the leptin gene showed statistically significant associations with CRC among women: LEP rs2167270 (OR = 1.13, 95% CI: 1.06-1.21) and LEP rs4731426 (OR = 1.09, 95% CI: 1.02-1.17). These associations remained significant after adjustment for obesity, suggesting that leptin SNPs may influence CRC risk independent of obesity. We observed statistically significant interactions of the leptin variants with hormone replacement therapy (HRT) for CRC risk; these variant associations were strengthened when analyses were restricted to post-menopausal women with low estrogen exposure, as estimated by 'never use' of HRT and/or non-obese BMI. No variants were associated with CRC among men. CONCLUSIONS:
Leptin gene variants may exhibit sex-specific associations with CRC risk. Endogenous and exogenous estrogen exposure may modify the association between these variants, leptin levels, and CRC risk.
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Authors | Kelsey A Chun, Jonathan M Kocarnik, Sheetal S Hardikar, Jamaica R Robinson, Sonja I Berndt, Andrew T Chan, Jane C Figueiredo, Noralane M Lindor, Mingyang Song, Robert E Schoen, Richard B Hayes, John D Potter, Rami Nassir, Stéphane Bézieau, Loic Le Marchand, Martha L Slattery, Emily White, Ulrike Peters, Polly A Newcomb |
Journal | PloS one
(PLoS One)
Vol. 13
Issue 10
Pg. e0206519
( 2018)
ISSN: 1932-6203 [Electronic] United States |
PMID | 30379922
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- ADIPOQ protein, human
- Adiponectin
- Leptin
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Topics |
- Adiponectin
(blood)
- Adult
- Aged
- Aged, 80 and over
- Body Mass Index
- Colorectal Neoplasms
(genetics, pathology)
- Female
- Genetic Association Studies
- Genetic Predisposition to Disease
- Genotype
- Humans
- Leptin
(blood, genetics)
- Male
- Middle Aged
- Polymorphism, Single Nucleotide
- Sex Factors
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