title: The Cumulative Effect of Gene-Gene and Gene-Environment Interactions on the Risk of Prostate Cancer in Chinese Men.
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.
authors.affiliation: Department of Cell Biology and Genetics, School of Basic Medical Science, Shanxi Medical University, Taiyuan 030001, China. lium0421@163.com.
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.affiliation: The Key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health, Beijing 100730, China. sxh_cnu@163.com.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Shi
authors.affiliation: The Key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health, Beijing 100730, China. zuoyeyf@163.com.|Graduate School, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100005, China. zuoyeyf@163.com.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Urology and Beijing Hospital, Chinese Ministry of Health, Beijing 100730, China. wangjy@bjhmoh.com.
authors.forename: Jianye
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin 300211, China. xuyong8816@sina.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Urology and Beijing Hospital, Chinese Ministry of Health, Beijing 100730, China. dongwei63@126.com.
authors.forename: Dong
authors.initials: D
authors.lastname: Wei
authors.affiliation: Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin 300211, China. ykuoster@126.com.
authors.forename: Kuo
authors.initials: K
authors.lastname: Yang
authors.affiliation: Department of Urology and Beijing Hospital, Chinese Ministry of Health, Beijing 100730, China. zhangyaoguang2005@hotmail.com.
authors.forename: Yaoguang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Urology and Beijing Hospital, Chinese Ministry of Health, Beijing 100730, China. wangxingemini@163.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: The Key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health, Beijing 100730, China. baobaocathh@163.com.
authors.forename: Siying
authors.initials: S
authors.lastname: Liang
authors.affiliation: Department of Urology and Beijing Hospital, Chinese Ministry of Health, Beijing 100730, China. 18600405631@163.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.affiliation: The Key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health, Beijing 100730, China. sunbmu@foxmail.com.
authors.forename: Liang
authors.initials: L
authors.lastname: Sun
authors.affiliation: The Key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health, Beijing 100730, China. zhuxqyy@gmail.com.
authors.forename: Xiaoquan
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Cell Biology and Genetics, School of Basic Medical Science, Shanxi Medical University, Taiyuan 030001, China. 13934662586@outlook.com.|The Key Laboratory of Geriatrics, Beijing Hospital &amp; Beijing Institute of Geriatrics, Ministry of Health, Beijing 100730, China. 13934662586@outlook.com.
authors.forename: Chengxiao
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Medical Examination Centre, Beijing Hospital, Ministry of Health, Beijing 100730, China. zhuling8899@hotmail.com.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhu
authors.affiliation: The Key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health, Beijing 100730, China. tanglei1974@hotmail.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Tang
authors.affiliation: Guangxi Zhuang Autonomous Region Women and Children Care Hospital, Nanning, Guangxi 530003, China. oushangenetics2012@163.com.
authors.forename: Chenguang
authors.initials: C
authors.lastname: Zheng
authors.affiliation: The Key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health, Beijing 100730, China. yang_ze@sina.com.
authors.forename: Ze
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects*; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D015992:Body Mass Index; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D054526:Men's Health; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000235:genetics*; D012306:Risk; D012907:Smoking / Q000009:adverse effects; D011795:Surveys and Questionnaires
keywords: gene-environment interaction; gene-gene interaction; prostate cancer; single nucleotide polymorphism
references.citation: Nat Genet. 2009 Oct;41(10):1122-6
references.pmid: 19767754
references.citation: J Natl Cancer Inst. 2009 Oct 7;101(19):1330-6
references.pmid: 19726753
references.citation: Hum Genet. 2012 Jul;131(7):1225-34
references.pmid: 22367438
references.citation: Ann Oncol. 2012 Jul;23(7):1665-71
references.pmid: 22228452
references.citation: J Natl Cancer Inst. 2012 Nov 7;104(21):1647-59
references.pmid: 23104210
references.citation: Int J Cancer. 2013 May 1;132(9):2176-85
references.pmid: 23024014
references.citation: Eur Urol. 2013 May;63(5):800-9
references.pmid: 23219374
references.citation: Asian J Androl. 2013 May;15(3):309-13
references.pmid: 23564043
references.citation: Prostate. 2013 Oct;73(14):1518-28
references.pmid: 23824512
references.citation: Nat Rev Urol. 2014 Jan;11(1):18-31
references.pmid: 24296704
references.citation: Nat Genet. 2014 Feb;46(2):126-35
references.pmid: 24390282
references.citation: PLoS One. 2014;9(2):e89508
references.pmid: 24586834
references.citation: Biomed Environ Sci. 2014 Sep;27(9):707-17
references.pmid: 25256860
references.citation: Lancet Oncol. 2014 Oct;15(11):e484-92
references.pmid: 25281467
references.citation: Eur Urol. 2014 Dec;66(6):1133-8
references.pmid: 24568894
references.citation: Cancer Epidemiol Biomarkers Prev. 2015 Jan;24(1):213-20
references.pmid: 25342390
references.citation: PLoS One. 2015;10(5):e0125534
references.pmid: 25942446
references.citation: N Engl J Med. 2000 Jul 13;343(2):78-85
references.pmid: 10891514
references.citation: Ann N Y Acad Sci. 2000 Jun;910:85-104; discussion 104-5
references.pmid: 10911908
references.citation: Epidemiol Rev. 2001;23(1):163-7
references.pmid: 11588843
references.citation: Biochim Biophys Acta. 2003 Jun 19;1627(2-3):147-52
references.pmid: 12818433
references.citation: Stat Med. 1994 Jan 30;13(2):153-62
references.pmid: 8122051
references.citation: Nat Genet. 2006 Jun;38(6):652-8
references.pmid: 16682969
references.citation: Science. 2006 Oct 13;314(5797):268-74
references.pmid: 16959974
references.citation: Nat Genet. 2007 May;39(5):645-9
references.pmid: 17401363
references.citation: Prostate. 2010 Mar 1;70(4):425-32
references.pmid: 19866473
references.citation: Prostate. 2010 Apr 1;70(5):502-7
references.pmid: 19908238
references.citation: Nat Genet. 2010 Sep;42(9):751-4
references.pmid: 20676098
references.citation: PLoS One. 2011;6(2):e16981
references.pmid: 21386969
references.citation: Cancer Epidemiol. 2011 Aug;35(4):e18-24
references.pmid: 21094112
references.citation: Hum Hered. 2011;72(3):182-93
references.pmid: 22086326
references.citation: J Urol. 2012 Jan;187(1):315-21
references.pmid: 22099997
references.citation: Cancer Epidemiol Biomarkers Prev. 2012 Jan;21(1):212-6
references.pmid: 22056501
references.citation: PLoS One. 2012;7(5):e37866
references.pmid: 22662242
references.citation: Nat Genet. 2007 May;39(5):631-7
references.pmid: 17401366
references.citation: Am J Hum Genet. 2007 Jun;80(6):1125-37
references.pmid: 17503330
references.citation: Nat Genet. 2007 Aug;39(8):977-83
references.pmid: 17603485
references.citation: N Engl J Med. 2008 Feb 28;358(9):910-9
references.pmid: 18199855
references.citation: Nat Genet. 2008 Mar;40(3):310-5
references.pmid: 18264096
references.citation: Nat Genet. 2008 Mar;40(3):316-21
references.pmid: 18264097
references.citation: Nat Genet. 2008 Mar;40(3):281-3
references.pmid: 18264098
references.citation: Cancer Epidemiol Biomarkers Prev. 2009 Jan;18(1):204-14
references.pmid: 19124499
references.citation: PLoS Genet. 2009 Aug;5(8):e1000597
references.pmid: 19680443
references.citation: Nat Genet. 2009 Oct;41(10):1058-60
references.pmid: 19767752
references.citation: Nat Genet. 2009 Oct;41(10):1116-21
references.pmid: 19767753