There is overwhelming evidence that inflammation plays a key role in the pathogenesis of cancer and its progression. Inflammation is regulated through a complex network of genes and polymorphic variants in these genes have been found to be associated to risk of various human cancers, alone or in combination with environmental variables. Despite this, not much is known on the genetic variability of genes that regulate inflammation and risk of pancreatic ductal adenocarcinoma (PDAC). We performed a two-phase association study considering the genetic variability of 76 genes that are key players in inflammatory response. We analysed tagging single nucleotide polymorphisms (SNPs) and regulatory SNPs on 7207 PDAC cases and 7063 controls and observed several associations with PDAC risk. The most significant association was between the carriers of the A allele of the CCL4-rs1719217 polymorphism, which was reported to be also associated with the expression level of the CCL4 gene, and increased risk of developing PDAC (odds ratio = 1.12, 95% confidence interval = 1.06-1.18, P = 3.34 × 10-5). This association was significant also after correction for multiple testing, highlighting the importance of using potentially functional SNPs in order to discover more genetic variants associated with PDAC risk.

中文翻译：

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炎症基因的遗传多态性和胰腺癌风险：对 14000 多名个体进行的两阶段研究。


大量证据表明炎症在癌症的发病机制及其进展中发挥着关键作用。炎症是通过复杂的基因网络进行调节的，这些基因中的多态性变体被发现与各种人类癌症的风险相关，无论是单独的还是与环境变量相结合。尽管如此，对于调节炎症和胰腺导管腺癌（PDAC）风险的基因的遗传变异性知之甚少。我们进行了一项两阶段关联研究，考虑了炎症反应中关键参与者的 76 个基因的遗传变异性。我们分析了 7207 个 PDAC 病例和 7063 个对照的标记单核苷酸多态性 (SNP) 和监管 SNP，并观察到与 PDAC 风险的几种关联。最显着的关联是 CCL4-rs1719217 多态性的 A 等位基因携带者之间的关联，据报道，该等位基因也与 CCL4 基因的表达水平相关，并且与发生 PDAC 的风险增加有关（比值比 = 1.12，95% 置信度）区间 = 1.06-1.18，P = 3.34 × 10-5)。经过多次测试校正后，这种关联也很重要，凸显了使用潜在功能性 SNP 来发现更多与 PDAC 风险相关的遗传变异的重要性。