Hold Georgina L, Rabkin Charles S, Gammon Marilie D, Berry Susan H, Smith Malcolm G, Lissowska Jolanta, Risch Harvey A, Chow Wong-Ho, Mowat N Ashley G, Vaughan Thomas L, El-Omar Emad M
Department of Medicine and Therapeutics, Aberdeen University, Foresterhill, Aberdeen, UK.
Eur J Cancer Prev. 2009 Apr;18(2):117-9. doi: 10.1097/CEJ.0b013e3283101292.
Host genetic factors play an important role in modifying the risk of human disease, including cancers of the upper gastrointestinal tract, with increasing interest in Toll-like receptor (TLR) signaling and the impact of genetic polymorphisms in these systems. The CD14-159C/T and the TLR9-1237T/C promoter polymorphisms have previously been shown to be associated with various inflammatory conditions including Helicobacter pylori-induced gastritis in Caucasian populations. In this study, we assessed the association of these two functional single nucleotide polymorphisms with gastric cancer in two independent Caucasian population-based case-control studies of upper gastrointestinal tract cancer, initially in 312 noncardia gastric carcinoma cases and 419 controls and then in 184 noncardia gastric carcinomas, 123 cardia carcinomas, 159 esophageal cancers, and 211 frequency-matched controls. Odds ratios were computed from logistic models and adjusted for potential confounding factors. No significant association was found between the CD14-159C/T and the TLR9-1237T/C promoter polymorphisms and increased risk of gastric cancer. Neither single nucleotide polymorphism has been assessed in a Caucasian gastric cancer case-control study before; although the CD14-159C/T polymorphism has been reported to show no apparent association with H. pylori-related gastric malignancy in a Taiwanese Chinese population. In conclusion, although our earlier preliminary studies suggested that the CD14-159C/T and the TLR9-1237T/C promoter polymorphisms increase the risk of precancerous outcomes, they do not seem to increase the risk of gastric cancer itself. This discrepancy merits further examination.
宿主遗传因素在改变人类疾病风险方面发挥着重要作用，包括上消化道癌症，人们对Toll样受体（TLR）信号传导以及这些系统中基因多态性的影响越来越感兴趣。先前已表明，CD14 - 159C/T和TLR9 - 1237T/C启动子多态性与包括白种人群中幽门螺杆菌诱导的胃炎在内的各种炎症性疾病有关。在本研究中，我们在两项基于白种人群的上消化道癌症独立病例对照研究中评估了这两种功能性单核苷酸多态性与胃癌的关联，最初是在312例非贲门胃癌病例和419例对照中进行，然后是在184例非贲门胃癌、123例贲门癌、s159例食管癌和211例频率匹配的对照中进行。比值比通过逻辑模型计算，并针对潜在的混杂因素进行了调整。未发现CD14 - 159C/T和TLR9 - 1237T/C启动子多态性与胃癌风险增加之间存在显著关联。此前尚未在白种人胃癌病例对照研究中评估过这两种单核苷酸多态性；尽管据报道，在台湾华裔人群中，CD14 - 159C/T多态性与幽门螺杆菌相关的胃恶性肿瘤无明显关联。总之，尽管我们早期的初步研究表明CD14 - 159C/T和TLR9 - 1237T/C启动子多态性会增加癌前病变的风险，但它们似乎并不会增加胃癌本身的风险。这种差异值得进一步研究。
