title: Associations between smoking behavior-related alleles and the risk of melanoma.
abstract: 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.
authors.affiliation: Department of Epidemiology, Richard M. Fairbanks School of Public Health, Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, Indiana, USA.
authors.forename: Wenting
authors.initials: W
authors.lastname: Wu
authors.affiliation: Duke Cancer Institute, Duke School of Medicine, Durham, North Carolina, USA.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department 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.
authors.forename: Fengju
authors.initials: F
authors.lastname: Song
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Li-Shiun
authors.initials: LS
authors.lastname: Chen
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.|Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.|Department of Biostatistics, Harvard University School of Public Health, Boston, Massachusetts, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.affiliation: Duke Cancer Institute, Duke School of Medicine, Durham, North Carolina, USA.
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
authors.affiliation: Department of Epidemiology, Richard M. Fairbanks School of Public Health, Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, Indiana, USA.
authors.forename: Jiali
authors.initials: J
authors.lastname: Han
mesh_terms: D000328:Adult; D000483:Alleles; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1 / Q000235:genetics; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008545:Melanoma / Q000209:etiology*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D012907:Smoking / Q000009:adverse effects / Q000235:genetics*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; C517272:PDE1C protein, human
keywords: CHRNA5-A3-B4 gene cluster; case-control study; risk of melanoma; single-nucleotide polymorphisms (SNPs); smoking behavior