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Open AccessArticle

Alcohol Intake and Alcohol–SNP Interactions Associated with Prostate Cancer Aggressiveness

1
Biostatistics Program, School of Public Health, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
2
Behavioral and Community Health Sciences Program, School of Public Health, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
3
Department of Physiology, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
4
Comprehensive Alcohol Research Center, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
5
Biostatistics and Bioinformatics Shared Resource, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
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Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
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The Institute of Cancer Research, and The Royal Marsden NHS Foundation Trust, London SM2 5NG, UK
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Division of Population Health, Health Services Research, and Primary Care, University of Manchester, Oxford Road, Manchester M13 9PT, UK
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Department of Applied Health Research, University College London, London WC1E 7HB, UK
10
Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90015, USA
11
Norris Comprehensive Cancer Center, Los Angeles, CA 90015, USA
12
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany
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Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), D-69120 Heidelberg, Germany
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German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany
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Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
*
Author to whom correspondence should be addressed.
The Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome Consortium (PRACTICAL, http://practical.icr.ac.uk/), London SM2 5NG, UK. Additional members from The PRACTICAL Consortium were provided in the Supplementary Materials.
Academic Editor: Wojciech Krajewski
J. Clin. Med. 2021, 10(3), 553; https://doi.org/10.3390/jcm10030553
Received: 3 December 2020 / Revised: 25 January 2021 / Accepted: 28 January 2021 / Published: 2 February 2021
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. View Full-Text
Keywords: alcohol intake; SNP interaction; prostate cancer alcohol intake; SNP interaction; prostate cancer
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MDPI and ACS Style

Lin, H.-Y.; Wang, X.; Tseng, T.-S.; Kao, Y.-H.; Fang, Z.; Molina, P.E.; Cheng, C.-H.; Berglund, A.E.; Eeles, R.A.; Muir, K.R.; Pashayan, N.; Haiman, C.A.; Brenner, H.; Park, J.Y.; The PRACTICAL Consortium. Alcohol Intake and Alcohol–SNP Interactions Associated with Prostate Cancer Aggressiveness. J. Clin. Med. 2021, 10, 553. https://doi.org/10.3390/jcm10030553

AMA Style

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, Park JY, The PRACTICAL Consortium. Alcohol Intake and Alcohol–SNP Interactions Associated with Prostate Cancer Aggressiveness. Journal of Clinical Medicine. 2021; 10(3):553. https://doi.org/10.3390/jcm10030553

Chicago/Turabian Style

Lin, Hui-Yi; Wang, Xinnan; Tseng, Tung-Sung; Kao, Yu-Hsiang; Fang, Zhide; Molina, Patricia E.; Cheng, Chia-Ho; Berglund, Anders E.; Eeles, Rosalind A.; Muir, Kenneth R.; Pashayan, Nora; Haiman, Christopher A.; Brenner, Hermann; Park, Jong Y.; The PRACTICAL Consortium. 2021. "Alcohol Intake and Alcohol–SNP Interactions Associated with Prostate Cancer Aggressiveness" J. Clin. Med. 10, no. 3: 553. https://doi.org/10.3390/jcm10030553

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