Associations between smoking behavior-related alleles and the risk of melanoma
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Wenting Wu1, Hongliang Liu2, Fengju Song3, Li-Shiun Chen4, Peter Kraft5,6,7, Qingyi Wei2, Jiali Han1
1Department of Epidemiology, Richard M. Fairbanks School of Public Health, Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, Indiana, USA
2Duke Cancer Institute, Duke School of Medicine, Durham, North Carolina, USA
3Department of Epidemiology and Biostatistics, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Centre of Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, P. R. China
4Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA
5Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA
6Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA
7Department of Biostatistics, Harvard University School of Public Health, Boston, Massachusetts, USA
Jiali Han, email: [email protected]
Keywords: risk of melanoma, smoking behavior, single-nucleotide polymorphisms (SNPs), case-control study, CHRNA5-A3-B4 gene cluster
Received: May 09, 2016 Accepted: June 06, 2016 Published: June 17, 2016
Several studies have reported that cigarette smoking is inversely associated with the risk of melanoma. This study further tested whether incorporating genetic factors will provide another level of evaluation of mechanisms underlying the association between smoking and risk of melanoma. We investigated the association between SNPs selected from genome-wide association studies (GWAS) on smoking behaviors and risk of melanoma using 2,298 melanoma cases and 6,654 controls. Among 16 SNPs, three (rs16969968 [A], rs1051730 [A] and rs2036534 [C] in the 15q25.1 region) reached significance for association with melanoma risk in men (0.01 < = P values < = 0.02; 0.85 < = Odds Ratios (ORs) <= 1.20). There was association between the genetic scores based on the number of smoking behavior-risk alleles and melanoma risk with P-trend = 0.005 among HPFS. Further association with smoking behaviors indicating those three SNPs (rs16969968 [A], rs1051730 [A] and rs2036534 [C]) significantly associated with number of cigarettes smoked per day, CPD, with P = 0.009, 0.011 and 0.001 respectively. The SNPs rs215605 in the PDE1C gene and rs6265 in the BDNF gene significantly interacted with smoking status on melanoma risk (interaction P = 0.005 and P = 0.003 respectively). Our study suggests that smoking behavior-related SNPs are likely to play a role in melanoma development and the potential public health importance of polymorphisms in the CHRNA5-A3-B4 gene cluster. Further larger studies are warranted to validate the findings.
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