Citrus-Gene interaction and melanoma risk in the UK Biobank.

High citrus consumption may increase melanoma risk; however, little is known about the biological mechanisms of this association, or whether it is modified by genetic variants. We conducted a genome-wide analysis of gene-citrus consumption interactions on melanoma risk among 1563 melanoma cases and 193 296 controls from the UK Biobank. Both the 2-degrees-of-freedom (df) joint test of genetic main effect and gene-environment (G-E) interaction and the standard 1-df G-E interaction test were performed. Three index SNPs (lowest P-value SNP among highly correlated variants [r2  > .6]) were identified from among the 365 genome-wide significant 2-df test results (rs183783391 on chromosome 3 [MITF], rs869329 on chromosome 9 [MTAP] and rs11446223 on chromosome 16 [DEF8]). Although all three were statistically significant for the 2-df test (4.25e-08, 1.98e-10 and 4.93e-13, respectively), none showed evidence of interaction according to the 1-df test (P = .73, .24 and .12, respectively). Eight nonindex, 2-df test significant SNPs on chromosome 16 were significant (P < .05) according to the 1-df test, providing evidence of citrus-gene interaction. Seven of these SNPs were mapped to AFG3L1P (rs199600347, rs111822773, rs113178244, rs3803683, rs73283867, rs78800020, rs73283871), and one SNP was mapped to GAS8 (rs74583214). We identified several genetic loci that may elucidate the association between citrus consumption and melanoma risk. Further studies are needed to confirm these findings.