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Int. J. Environ. Res. Public Health 2016, 13(2), 162; doi:10.3390/ijerph13020162

The Cumulative Effect of Gene-Gene and Gene-Environment Interactions on the Risk of Prostate Cancer in Chinese Men

1
Department of Cell Biology and Genetics, School of Basic Medical Science, Shanxi Medical University, Taiyuan 030001, China
2
The Key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health, Beijing 100730, China
3
Graduate School, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100005, China
4
Department of Urology and Beijing Hospital, Chinese Ministry of Health, Beijing 100730, China
5
Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin 300211, China
6
Medical Examination Centre, Beijing Hospital, Ministry of Health, Beijing 100730, China
7
Guangxi Zhuang Autonomous Region Women and Children Care Hospital, Nanning, Guangxi 530003, China
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Academic Editor: Paul B. Tchounwou
Received: 24 November 2015 / Revised: 15 January 2016 / Accepted: 18 January 2016 / Published: 27 January 2016
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Abstract

Prostate cancer (PCa) is a multifactorial disease involving complex genetic and environmental factors interactions. Gene-gene and gene-environment interactions associated with PCa in Chinese men are less studied. We explored the association between 36 SNPs and PCa in 574 subjects from northern China. Body mass index (BMI), smoking, and alcohol consumption were determined through self-administered questionnaires in 134 PCa patients. Then gene-gene and gene-environment interactions among the PCa-associated SNPs were analyzed using the generalized multifactor dimensionality reduction (GMDR) and logistic regression methods. Allelic and genotypic association analyses showed that six variants were associated with PCa and the cumulative effect suggested men who carried any combination of 1, 2, or ≥3 risk genotypes had a gradually increased PCa risk (odds ratios (ORs) = 1.79–4.41). GMDR analysis identified the best gene-gene interaction model with scores of 10 for both the cross-validation consistency and sign tests. For gene-environment interactions, rs6983561 CC and rs16901966 GG in individuals with a BMI ≥ 28 had ORs of 7.66 (p = 0.032) and 5.33 (p = 0.046), respectively. rs7679673 CC + CA and rs12653946 TT in individuals that smoked had ORs of 2.77 (p = 0.007) and 3.11 (p = 0.024), respectively. rs7679673 CC in individuals that consumed alcohol had an OR of 4.37 (p = 0.041). These results suggest that polymorphisms, either individually or by interacting with other genes or environmental factors, contribute to an increased risk of PCa. View Full-Text
Keywords: gene-gene interaction; gene-environment interaction; prostate cancer; single nucleotide polymorphism gene-gene interaction; gene-environment interaction; prostate cancer; single nucleotide polymorphism
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Liu, M.; Shi, X.; Yang, F.; Wang, J.; Xu, Y.; Wei, D.; Yang, K.; Zhang, Y.; Wang, X.; Liang, S.; Chen, X.; Sun, L.; Zhu, X.; Zhao, C.; Zhu, L.; Tang, L.; Zheng, C.; Yang, Z. The Cumulative Effect of Gene-Gene and Gene-Environment Interactions on the Risk of Prostate Cancer in Chinese Men. Int. J. Environ. Res. Public Health 2016, 13, 162.

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