When we stratified by sex, we observed stronger association between SNPs rs1051730, rs578776 and rs6495308 in the CHRNA3 gene, rs16969968 in the CHRNA5 gene, rs2036534 in HYKK gene and risk of melanoma among men in the HPFS (OR for rs1051730 = 0.77, 95% CI (0.60–0.97) (P = 0.03); 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). The gene discussed is HYKK; the disease is melanoma.