Department of Epidemiology, Indiana University Richard M. Fairbanks School of Public Health, Indianapolis, Indiana, USA.
Department of Epidemiology and Biostatistics, Indiana University School of Public health, Bloomington, Indiana, USA.
Int J Cancer. 2022 Mar 15;150(6):976-983. doi: 10.1002/ijc.33862. Epub 2021 Nov 6.
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 [r > .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.
高柑橘类水果摄入量可能会增加患黑色素瘤的风险；然而，人们对此关联的生物学机制知之甚少，也不清楚其是否会受到遗传变异的影响。我们在英国生物库中对 1563 例黑色素瘤病例和 193296 例对照进行了全基因组分析，以研究基因-柑橘类水果摄入相互作用与黑色素瘤风险之间的关系。我们同时进行了遗传主效和基因-环境（G-E）相互作用的双自由度（df）联合检验以及标准的 1-df G-E 相互作用检验。在 365 个具有全基因组显著意义的双自由度检验结果中（rs183783391 位于第 3 号染色体[MITF]、rs869329 位于第 9 号染色体[MTAP]和 rs11446223 位于第 16 号染色体[DEF8]），我们从其中确定了三个索引 SNP（相关性最强的变异体中最低的 P 值 SNP [r > .6]）。尽管这三个 SNP 在双自由度检验中均具有统计学意义（分别为 4.25e-08、1.98e-10 和 4.93e-13），但根据单自由度检验，它们均未显示出相互作用的证据（分别为 P = .73、.24 和.12）。在第 16 号染色体上，有 8 个非索引 SNP 在双自由度检验中具有统计学意义（P < .05），根据单自由度检验，这提供了柑橘-基因相互作用的证据。这 8 个 SNP 中有 7 个映射到 AFG3L1P（rs199600347、rs111822773、rs113178244、rs3803683、rs73283867、rs78800020、rs73283871），一个 SNP 映射到 GAS8（rs74583214）。我们确定了几个遗传基因座，它们可能阐明柑橘类水果摄入与黑色素瘤风险之间的关联。需要进一步的研究来证实这些发现。
