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.
Highlights
Melanoma is the most lethal form of skin cancer
Further association with smoking behaviors indicating those three Single-nucleotide polymorphisms (SNP) significantly associated with number of cigarettes smoked per day, CPD, with P = 0.009, 0.011 and 0.001 respectively
When we stratified by sex, we observed stronger association between SNPs rs1051730, rs578776 and rs6495308 in the cholinergic receptor (CHRNA3) gene, rs16969968 in the cholinergic receptor (CHRNA5) gene, rs2036534 in HYKK gene and risk of melanoma among men in the Health Professionals Follow-up Study (HPFS) (OR for rs1051730 = 0.77, 95% confidence interval (CI) (0.60–0.97) (P = 0.03); Odds ratio (OR) for rs578776 = 1.44, 95% CI (1.14–1.80) (P = 0.002); OR for rs6495308 = 1.44, 95% CI (1.13–1.83) (P = 0.003); OR for rs16969968 =0.74, 95% CI (0.58–0.94) (P = 0.014); and OR for rs2036534= 1.39, 95% CI (1.09–1.77) (P = 0.008)
Summary
Melanoma is the most lethal form of skin cancer. Incidence and mortality due to melanoma are rising recently in whites [1]. The major host risk factors for melanoma include pigmentation phenotypes, number of melanocytic nevi and a family history of melanoma [2,3,4,5]. Though smoking is associated with an elevated risk of most cancers, some epidemiological studies have reported a decreased risk of cutaneous malignant melanoma (MM) among smokers [8,9,10,11]. Our previous finding showed an inverse association between smoking and melanoma risk, especially on the body site of head and neck [10]
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