Alcohol Intake and Alcohol-SNP Interactions Associated with Prostate Cancer Aggressiveness.
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Embargo End Date
ICR Authors
Authors
Lin, H-Y
Wang, X
Tseng, T-S
Kao, Y-H
Fang, Z
Molina, PE
Cheng, C-H
Berglund, AE
Eeles, RA
Muir, KR
Pashayan, N
Haiman, CA
Brenner, H
Consortium, TP
Park, JY
Wang, X
Tseng, T-S
Kao, Y-H
Fang, Z
Molina, PE
Cheng, C-H
Berglund, AE
Eeles, RA
Muir, KR
Pashayan, N
Haiman, CA
Brenner, H
Consortium, TP
Park, JY
Document Type
Journal Article
Date
2021-02-02
Date Accepted
2021-01-28
Abstract
Excessive alcohol intake is a well-known modifiable risk factor for many cancers. It is still unclear whether genetic variants or single nucleotide polymorphisms (SNPs) can modify alcohol intake's impact on prostate cancer (PCa) aggressiveness. The objective is to test the alcohol-SNP interactions of the 7501 SNPs in the four pathways (angiogenesis, mitochondria, miRNA, and androgen metabolism-related pathways) associated with PCa aggressiveness. We evaluated the impacts of three excessive alcohol intake behaviors in 3306 PCa patients with European ancestry from the PCa Consortium. We tested the alcohol-SNP interactions using logistic models with the discovery-validation study design. All three excessive alcohol intake behaviors were not significantly associated with PCa aggressiveness. However, the interactions of excessive alcohol intake and three SNPs (rs13107662 [CAMK2D, p = 6.2 × 10-6], rs9907521 [PRKCA, p = 7.1 × 10-5], and rs11925452 [ROBO1, p = 8.2 × 10-4]) were significantly associated with PCa aggressiveness. These alcohol-SNP interactions revealed contrasting effects of excessive alcohol intake on PCa aggressiveness according to the genotypes in the identified SNPs. We identified PCa patients with the rs13107662 (CAMK2D) AA genotype, the rs11925452 (ROBO1) AA genotype, and the rs9907521 (PRKCA) AG genotype were more vulnerable to excessive alcohol intake for developing aggressive PCa. Our findings support that the impact of excessive alcohol intake on PCa aggressiveness was varied by the selected genetic profiles.
Citation
Journal of clinical medicine, 2021, 10 (3)
Source Title
Publisher
MDPI
ISSN
2077-0383
eISSN
2077-0383
Research Team
Oncogenetics
Oncogenetics
Oncogenetics