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.

Genetic polymorphisms associated with smoking behaviour predict the risk of surgery in patients with Crohn's disease

“…Vice versa, protective effects of smoking in other conditions are also enhanced by smoking behaviour‐associated SNPs. Benefits of these SNPs in smokers include onset of Parkinson's disease at higher ages, protection regarding melanoma, a lower body mass index and lower rates of knee replacements . In line with our study, odds ratio of 1.1‐1.9 per risk allele were observed.…”

“…The association of rs6265‐T with ileal disease location might therefore be due to earlier smoking in our rs6265‐T patients, triggering and shaping an immunological response at a vulnerable age. Interestingly, rs6265‐T enhanced protective effects of smoking in melanoma and increased the risk of childhood asthma . Several lines of evidence also indicate a direct role of brain‐derived neurotrophic factor (BDNF) on the immune and nervous system of the gut .…”

Cigarette Smoking and the Risk of Cutaneous Melanoma: A Case-Control Study

“…Recently, it has been discovered that genetic predisposition exists for smoking behavior [35,36]. In a subsequent study an inverse association between smoking behavior-related genetic variants in the chromosome 15q25.1 region and risk of melanoma, especially in males, was observed [37]. This suggests that smoking behaviorrelated single nucleotide polymorphisms play a role in melanoma development and might indicate that smoking is indeed causally related to melanoma risk.…”

Epigenetic and Environmental Risk Factors in Skin Cancer

“…Çevre kirliliğinin DNA metilasyonunda değişikliklere neden olduğu tespit edilmiştir (Silva et al, 2019). Sigaranın SHK için risk faktörü olduğu, melanomda da sentinal lenf nodu metastazı ile sigara içimi arasında ilişki bulunduğu bildirilmiştir (Ortiz and Grando, 2012;Wu et al, 2016;Jones et al, 2017). Joehanes ve ark.…”