Alcohol Intake and Alcohol-SNP Interactions Associated with Prostate Cancer Aggressiveness.

Hui-Yi Lin,Hermann Brenner,Kenneth R Muir,Chia-Ho Cheng,Xinnan Wang,Yu-Hsiang Kao,Jong Y Park,Nora Pashayan,Rosalind A Eeles,Patricia E Molina,Zhide Fang,Anders E Berglund,Christopher A Haiman,Tung-Sung Tseng

doi:10.3390/jcm10030553

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.

Highlights

Prostate cancer (PCa) is the most common cancer, and the second leading cause of cancer deaths among men in the United States [1] and the sixth cause of cancer-related deaths among men in highly developed regions worldwide [2]
To test whether single nucleotide polymorphisms (SNPs) in the four pathways influenced the associations between excessive alcohol intake impact and prostate cancer (PCa) aggressiveness, we evaluated a total of 7501 alcohol–SNP interaction tests for each of the alcohol outcomes in the discovery set
This study examined the alcohol–SNP interactions in the four pathways associated with PCa aggressiveness

Summary

Introduction

Prostate cancer (PCa) is the most common cancer, and the second leading cause of cancer deaths among men in the United States [1] and the sixth cause of cancer-related deaths among men in highly developed regions worldwide [2]. It is commonly accepted that a complex interplay between genetic and environmental factors plays a role in cancer prognosis [3,4]. Both environmental and genetic factors play essential roles in PCa etiology [5,6,7]. Alcohol intake is one of the potentially modifiable factors associated with PCa aggressiveness and prognosis. A meta-analysis study revealed alcohol consumption to be associated with an increased risk of PCa aggressiveness [13]. Associations between alcohol use and PCa aggressiveness remain inconclusive [14,15]

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Conclusion