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目的:探讨血清叶酸代谢关键酶亚甲基四氢叶酸还原酶(MTHFR)与胸腺嘧啶合成酶(TS)基因多态性与食管及贲门癌易感性的关系。方法:选取安阳地区病理证实的275例食管鳞癌(SCC)及129例贲门腺癌(GCA)患者和315例年龄性别与其匹配的正常对照人群,采用PCR基础上的限制性片段多态检测法(PCR-RFLP)对其NTHFR和TS各基因型进行分析。结果:①对照组MTHFR677CC、CT及TT基因型的分布频率分别为24%、45%和31%;SCC组分别为19%、38%和43%;GCA组分别为19%、35%和46%。对照组TSER3R/3R(4R)、2R/3R及2R/2R基因型的分布频率分别为64%、34%和2%;SCC组分别为62%、35%和4%;在GCA组,分别为63%、30%以及7%。②与MTHFR677CC及MTHFR677CT两基因型相比,TT携带者患SCC的危险度升高1.62倍(OR=1.62,95%可信区间(CI)为1.15~2.30,P=0.006),而GCAOR=1.81(95%CI为1.17~2.81,P=0.008)。③与其他基因型相比,纯合突变型(TSER2R/2R)患SCC的危险度升高2.44倍(OR=2.44,95%CI为0.89~6.73,P=0.084),患GCA的危险度升高3.94倍(OR=3.94,95%CI为1.29~12.0,P=0.016)。④相对于无基因突变者,仅有MTHFR677TT者患SCC的危险度升高1.60倍(95%CI为1.13~2.28),患GCA的危险度升高1.84倍(95%CI为1.17~2.88),仅有TSER2R/2R者患SCC的危险度升高1.89倍(95%CI为0.62~5.79),差异无统计学意义,但患GCA的危险度升高3.56倍(95%CI为1.03~12.3),双突变型组合(MTHFR677TT和TSER2R/2R)携带者在SCC组中占1.5%,在GCA组中占3.1%,在对照组中未检测到。结论:突变型MTHFR677TT及TSER2R/2R增加安阳地区人群SCC与GCA的易感性,当二者共同存在时,肿瘤的易感性更高。MTHFR与TS基因多态的存在可能是SCC与GCA地理分布一致性的遗传学基础之一。
Objective: To investigate the relationship between polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and thymine synthase (TS), a key enzyme involved in the metabolism of serum folate, and the susceptibility of esophageal and gastric cardia cancer. Methods: A total of 275 cases of esophageal squamous cell carcinoma (SCC) and 129 cases of gastric cardia adenocarcinoma (GCA) confirmed by pathology in the Anyang area and 315 age-matched controls were selected. The restriction fragment polymorphism (PCR-RFLP) to analyze its NTHFR and TS genotypes. Results: ① The distribution frequencies of MTHFR677CC, CT and TT genotypes were 24%, 45% and 31% in control group, 19%, 38% and 43% in SCC group and 19%, 35% and 46% in GCA group %. The frequencies of TSER3R / 3R (4R), 2R / 3R and 2R / 2R genotypes were 64%, 34% and 2% in the control group, 62%, 35% and 4% in the SCC group, respectively 63%, 30% and 7%. ② Compared with MTHFR677CC and MTHFR677CT genotypes, TT carriers had a 1.62-fold increased risk of developing SCC (OR = 1.62, 95% confidence interval (CI) = 1.15-2.30, P = 0.006) (95% CI 1.17-2.81, P = 0.008). ③ Compared with other genotypes, the risk of SCC in TSER2R / 2R increased 2.44-fold (OR = 2.44, 95% CI 0.89 to 6.73, P = 0.084), and the risk of GCA increased 3.94 times higher (OR = 3.94, 95% CI 1.29 to 12.0, P = 0.016). ④ Compared with those without gene mutation, the risk of SCC in MTHFR677TT patients was 1.60 times higher (95% CI: 1.13-2.28) and 1.84 times (95% CI: 1.17-2.88), respectively. The TSER2R / 2R only had a 1.89-fold increased risk of developing SCC (95% CI, 0.62-5.79) with no significant difference but with a 3.56-fold increased risk of GCA (95% CI, 1.03-12.3) (MTHFR677TT and TSER2R / 2R) carriers accounted for 1.5% in the SCC group and 3.1% in the GCA group and not in the control group. CONCLUSION: Mutant MTHFR677TT and TSER2R / 2R increase the susceptibility of SCC and GCA in Anyang area. When the two are present together, the tumor is more susceptible. The presence of MTHFR and TS gene polymorphisms may be one of the genetic bases for the consistent geographic distribution of SCC and GCA.