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Background  Melanoma is the most aggressive type of skin cancer and is associated with environmental and genetic risk factors. It originates in melanocytes, the pigment-producing cells. Single nucleotide polymorphisms (SNPs) in pigmentation genes have been described in melanoma risk modulation, but knowledge in the field is still limited.    Methods  In a case-control approach (107 cases and 119 controls), we investigated the effect of four pigmentation gene SNPs ( TYR  rs1126809,  HERC2  rs1129038,  SLC24A5  rs1426654, and  SLC45A2  rs16891982) on melanoma risk in individuals from southern Brazil using a multivariate logistic regression model and multifactor dimensionality reduction (MDR) analysis.    Results  Two SNPs were associated with an increased risk of melanoma in a dominant model: rs1129038AA and rs1426654AA [OR = 2.094 (95% CI: 1.106–3.966),  P  = 2.3 10 − 2  and OR = 7.126 (95% CI: 1.873–27.110),  P  = 4.0 10 − 3 , respectively]. SNP rs16891982CC was associated with a lower risk to melanoma development in a log-additive model when the allele C was inherited [OR = 0.081 (95% CI: 0.008–0.782),  P  = 3 10 − 2 ]. In addition, MDR analysis showed that the combination of the rs1426654AA and rs16891982GG genotypes was associated with a higher risk for melanoma ( P  = 3 10 − 3 ), with a redundant effect.    Conclusions  These results contribute to the current knowledge and indicate that epistatic interaction of these SNPs, with an additive or correlational effect, may be involved in modulating the risk of melanoma in individuals from a geographic region with a high incidence of the disease.

Skin pigmentation polymorphisms associated with increased risk of melanoma in a case-control sample from southern Brazil