A few single-nucleotide polymorphisms (SNPs) have been identified to be associated with cutaneous melanoma (CM) survival through genome-wide association studies, but stringent multiple testing corrections required for the hypothesis-free testing may have masked some true associations. Using a hypothesis-driven analysis approach, we sought to evaluate associations between SNPs in ketone body metabolic pathway genes and CM survival. We comprehensively assessed associations between 4196 (538 genotyped and 3658 imputed) common SNPs in 44 ketone body metabolic pathway genes and CM survival, using a dataset of 858 patients of a case-control study from The University of Texas M.D. Anderson Cancer Center as the discovery set and another dataset of 409 patients from the Nurses' Health Study and the Health Professionals Follow-up Study as the replication set. There were 95/858 (11.1%) and 48/409 (11.7%) patients who died of CM, respectively. We identified two independent SNPs (ie, PDSS1 rs12254548 G>C and SLC16A6 rs71387392 G>A) that were associated with CM survival, with allelic hazards ratios of 0.58 (95% confidence interval [CI] = 0.44-0.76, P = 9.00 × 10-5 ) and 1.98 (95% CI = 1.34-2.94, P = 6.30 × 10-4 ), respectively. Additionally, associations between genotypes of the SNPs and messenger RNA expression levels of their corresponding genes support the biologic plausibility of a role for these two variants in CM tumor progression and survival. Once validated by other larger studies, PDSS1 rs12254548 and SLC16A6 rs71387392 may be valuable biomarkers for CM survival.

中文翻译：

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酮体代谢途径 PDSS1 和 SLC16A6 的遗传变异可预测皮肤黑色素瘤特异性存活。


通过全基因组关联研究，一些单核苷酸多态性 (SNP) 已被确定与皮肤黑色素瘤 (CM) 存活相关，但无假设测试所需的严格多重测试校正可能掩盖了一些真正的关联。使用假设驱动的分析方法，我们试图评估酮体代谢途径基因中的 S​​NP 与 CM 存活率之间的关联。我们使用德克萨斯大学 MD 安德森癌症中心的病例对照研究的 858 名患者数据集，全面评估了 44 个酮体代谢途径基因中的 4196 个（538 个基因分型和 3658 个估算）常见 SNP 与 CM 生存之间的关联。集和来自护士健康研究和健康专业人员随访研究的 409 名患者的另一个数据集作为复制集。分别有 95/858 (11.1%) 和 48/409 (11.7%) 患者死于 CM。我们确定了两个与 CM 存活相关的独立 SNP（即 PDSS1 rs12254548 G>C 和 SLC16A6 rs71387392 G>A），等位基因风险比为 0.58（95% 置信区间 [CI] = 0.44-0.76，P = 9.00 × 10-5）和 1.98（95% CI = 1.34-2.94，P = 6.30 × 10-4）。此外，SNP 的基因型与其相应基因的信使 RNA 表达水平之间的关联支持这两种变异在 CM 肿瘤进展和生存中的作用的生物学合理性。一旦得到其他大型研究的验证，PDSS1 rs12254548 和 SLC16A6 rs71387392 可能是 CM 生存的有价值的生物标志物。