Variants in melanogenesis‐related genes associate with skin cancer risk among J apanese populations

Human skin color is known to be associated with the risk of cutaneous cancer. Some reports indicated that pigmentation‐related gene variants were associated with cutaneous cancer risk in C aucasian populations, but there are no similar reports in East A sian populations. This study aimed to evaluate the association between pigmentation‐related genes and the risk of skin cancer in J apanese populations. We studied the associations between 12 variants of four pigmentation‐related genes and melanin index variations in 198 J apanese patients with skin cancer and compared these findings to those of 500 J apanese controls by using multiple logistic regression analysis. Furthermore, we analyzed an independent sample of 107 J apanese patients with skin cancer. A non‐synonymous variant, H615R in the oculocutaneous albinism 2 gene ( OCA 2 ), was associated with the risk of malignant melanoma in the Y amagata group (odds ratio [ OR ], 0.38; 95% confidence interval [ CI ], 0.17–0.86; P = 0.020). Another non‐synonymous variant, A481T in OCA 2 , was associated with the risk of squamous cell carcinoma and actinic keratosis in the O saka group ( OR , 3.16; 95% CI , 1.41–7.04; P = 0.005). In malignant melanoma cases, the minor allele in OCA 2 H615R might have induced the development of lesions in sun‐exposed skin ( OR , 26.32; 95% CI , 1.96–333; P = 0.014). Our results suggest that some OCA 2 variants are definite risk factors for the onset of cutaneous cancer in J apanese populations.