Pancreatic ductal adenocarcinoma is an aggressive and relatively rare cancer with a dismal 5-year survival rate and a clear genetic background. Genetic variants in taste receptors and taste-related genes have been associated with a variety of human traits and phenotypes among which several cancer types and pancreatic cancer risk factors. In this study, we analysed 2854 single-nucleotide polymorphisms in 50 taste-related genes, including 37 taste receptors. To cover all the genetic variability of the selected genes and to include also regulatory elements, we added 5000 nucleotides to both ends of each gene. We used a two-phase approach, with the PanScan data set (3314 cases and 3431 controls) as the discovery phase and PanC4 (3893 cases and 3632 controls) as validation phase, for a total of 7207 cases and 7063 controls. The datasets were downloaded from the NCBI database of genotypes and phenotypes (dbGaP). We observed that the taste 1 receptor member 2 (TAS1R2)-rs11261087 variant was associated with pancreatic cancer risk in both phases independently, with a consistent association of the T allele with decreased risk of developing the disease [phase 1 odds ratio (OR) = 0.89, 95% confidence interval (CI) 0.80-0.98; phase 2 OR = 0.91, 95% CI 0.83-0.99; all subjects together OR = 0.90, 95% CI 0.84-0.96, P = 0.002]. However, neither the association observed in the validation phase nor those observed in the joint analysis were statistically significant considering multiple testing. Functional studies are warranted to better understand the impact of the genetic variability of TAS1R2 on PDAC risk.

中文翻译：

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味觉相关基因的遗传变异与胰腺癌的风险。


胰腺导管腺癌是一种侵袭性且相对罕见的癌症，其 5 年生存率很低，且有明确的遗传背景。味觉受体和味觉相关基因的遗传变异与多种人类特征和表型相关，其中包括几种癌症类型和胰腺癌危险因素。在这项研究中，我们分析了 50 个味觉相关基因（包括 37 个味觉受体）的 2854 个单核苷酸多态性。为了涵盖所选基因的所有遗传变异性并包括调控元件，我们在每个基因的两端添加了 5000 个核苷酸。我们采用两阶段方法，以 PanScan 数据集（3314 例病例和 3431 例对照）作为发现阶段，以 PanC4（3893 例病例和 3632 例对照）作为验证阶段，总共 7207 例病例和 7063 例对照。数据集是从 NCBI 基因型和表型数据库 (dbGaP) 下载的。我们观察到，味觉 1 受体成员 2 (TAS1R2)-rs11261087 变异与两个阶段的胰腺癌风险独立相关，T 等位基因与患该疾病的风险降低具有一致的关联[第 1 阶段优势比 (OR) = 0.89，95%置信区间（CI）0.80-0.98； 2 期 OR = 0.91，95% CI 0.83-0.99；所有受试者合计 OR = 0.90，95% CI 0.84-0.96，P = 0.002]。然而，考虑到多重测试，验证阶段观察到的关联和联合分析中观察到的关联都不具有统计显着性。有必要进行功能研究，以更好地了解 TAS1R2 遗传变异对 PDAC 风险的影响。