Zhuang Wen, Wu Xiao-Ting, Zhou Yong, Liu Guan-Jian, Wu Tai-Xiang, Yao Xun, Du Liang, Wei Mao-Ling
Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, 37 Guo Xue Rd, Chengdu, Sichuan Province, 610041, China.
Dig Dis Sci. 2009 Jul;54(7):1379-85. doi: 10.1007/s10620-008-0511-8. Epub 2008 Nov 7.
Studies investigating the association of polymorphisms in the 5'-untranslated regions (5'UTR) and 3'-untranslated regions (3'UTR) of thymidylate synthase with gastric cancer susceptibility and sensitivity to fluoropyrimidine-based chemotherapy report conflicting results. The objective of this study was to quantitatively summarize the evidence for such a relationship. This meta-analysis included ten studies, which included 1,730 gastric cancer cases and 1,843 controls. The combined results based on all studies showed that there was no significant difference in genotype distribution of 5'UTR or 3'UTR between gastric cancer and noncancer patients. When stratifying for race, we found that: (1) among Asians, patients with gastric cancer had significantly higher frequency of 2R/2R of 5'UTR than did noncancer patients, and (2) among Caucasians, patients with gastric cancer had significantly lower frequency of ins6/ins6 and higher frequency of ins6/del6 of 3'UTR than did noncancer patients. No significantly different response rate or survival of gastric cancer with fluoropyrimidine-based chemotherapy were observed with genotype distribution of 5'UTR or 3'UTR among Caucasians or Asians. This meta-analysis suggests that polymorphisms in the 5'UTR and 3'UTR of thymidylate synthase may be associated with gastric cancer susceptibility, but are not correlated with sensitivity of gastric cancer to fluoropyrimidine-based chemotherapy.
关于胸苷酸合成酶5'-非翻译区（5'UTR）和3'-非翻译区（3'UTR）多态性与胃癌易感性及对氟嘧啶类化疗敏感性之间关联的研究报告结果相互矛盾。本研究的目的是定量总结这种关系的证据。该荟萃分析纳入了10项研究，包括1730例胃癌病例和1843例对照。基于所有研究的合并结果显示，胃癌患者与非癌症患者在5'UTR或3'UTR的基因型分布上无显著差异。按种族分层时，我们发现：（1）在亚洲人中，胃癌患者5'UTR的2R/2R频率显著高于非癌症患者；（2）在白种人中，胃癌患者3'UTR的ins6/ins6频率显著低于非癌症患者，而ins6/del6频率则显著高于非癌症患者。在白种人或亚洲人中，5'UTR或3'UTR的基因型分布与基于氟嘧啶的化疗的胃癌反应率或生存率无显著差异。该荟萃分析表明，胸苷酸合成酶5'UTR和3'UTR的多态性可能与胃癌易感性相关，但与胃癌对氟嘧啶类化疗的敏感性无关。
