胃癌亚甲基四氢叶酸还原酶基因多态性及其与微卫星不稳的关系

司佩任; 房殿春; 张浩; 杨柳芹; 罗元辉; 廖化禹

Abstract

司佩任,房殿春,张浩,杨柳芹,罗元辉,廖化禹.胃癌亚甲基四氢叶酸还原酶基因多态性及其与微卫星不稳的关系[J].Chinese journal of Epidemiology,2005,26(10):794-799

胃癌亚甲基四氢叶酸还原酶基因多态性及其与微卫星不稳的关系

The relationship between methylenetetrahydrofolate reductase gene polymorphism and microsatellite instability in gastric cancer

Received:December 16, 2004

DOI：

KeyWord: 胃肿瘤亚甲基四氢叶酸还原酶微卫星不稳

English Key Word: Gastric neoplasm Methylenetetrahydrofolate reductase Microsatellite instability

FundProject:国家自然科学基金项目(30070043)；军队“十五”科研基金重点项目(01Z075)

Author Name	Affiliation	E-mail
SI Pei-ren	264000 烟台,解放军第一○七医院消化科
FANG Dian-chun	Department of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China	fangdianchun@hotmail.com
ZHANG Hao	Department of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China
YANG Liu-qin	Department of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China
LUO Yuan hui	Department of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China
LIAO Hua-yu	Department of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China

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Abstract:

目的探讨胃癌亚甲基四氢叶酸还原酶(MTHFR)基因多态性与微卫星不稳的关系。方法采用聚合酶链反应．限制性片段长度多态性技术检测122例胃癌和101名正常对照的MTHFR 基因C677T和A1298C多态性；采用PCR为基础的方法检测微卫星不稳定性(MSI)。结果 MTHFR C677T多态性可分为677CC、677CT和677TT三种类型。胃癌组3种基因型频率分别为47．5％、39．3％和13．1％;对照组分别为48．5％、42．6％和8．9％，两组相比差异无统计学意义(P＞0．05)。以677CC基因型做为参考，胃贲门癌677CT基因型OR值为0．38，95％CI：0．15～0．98；TT 基因型OR值为0．26，95％CI：0．03～2．18；677CT+TT基因型OR值为0．36，95％CI：0．07～0．98。胃体癌677TT基因型OR值为3．03，95％CI：1．07～8．65。MTHFR A1298C多态性可分为1298AA、1298AC和1298CC 3种类型。胃癌组3种基因型频率分别为59．8％、36．1％和4．1％；对照组分别为57．4％，37．6％和5．0％，两组相比差异无统计学意义(P＞0．05)。以1298AA基因型的OR值为1．00，胃窦癌AC基因型的OR值为0．87，95％CI：0．42～1．82，CC基因型的OR值为0．41，95％CI： 0．05～3．72。MTHFR 677TT基因型胃癌与微卫星不稳显著相关(P＜0．05)，而MTHFR A1298C多态性与微卫星不稳无关(P＞0．05)。结论重庆地区人群中MTHFR C677T多态性是胃贲门癌的保护因素，是胃体癌的危险因素；MTHFR A1298C多态性可能是胃窦癌的保护因素；677TT基因型胃癌的发生可能涉及到MSI途径。

English Abstract:

Objective To explore the relationship between Methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and microsatellite instability (MSI) in patients with gastric cancer. Methods MTHFR gene C677T and A1287C polymorphism were detected by polymerase chain reactionrestriction fragment length polymorphism (PCR-RFLP) and MSI was examined wit PCR. Results MTHFR gene C677T and A1298C polymorphisms were analyzed on 122 gastric cancerts and 110 normal controls. The genotype frequencies of MTHFR 677CC,677CT and 677TT were 47.5％,39.3％ and 13.1％ on patients with gastric cancer, and 48.5％,42.6％,8.9％ in the controls respectively. There was no significant difference of genotype frequency between the two guoups (P＞0.05). The individuals with 677CT genotype, 677TT genotype and 677CT+TT genotype exhibited significantly reduced risk (OR=0.38,95％CI:0.15-0.98; OR=0.26,95％CI:0.03-2.18 and OR=0.36,95％CI:0.07-0.98) of developing gastric cardia cancer compared with those harboring the wild-type(677CC).The individuals with 677TT genotype having a 3.03-fold(,95％CI:1.07-8.65) increased risk of developing gastric corpus cancer. The genotype frequency of Mthfr 1298AA,1298AC and 1298CC were 59.8%,36.1% and 4.1% in gastric cancer patients, and 57.4%, 7.6%,5.0% in the controls, respectively. The distribution of MTHFR A1298C genotype was not significantly different between gastric cancer and controls (P＞0.05). The individuals with 1298CC genotype had a reduced risk of developing gastric antrum cancer (OR=0.41-fold,95％CI:0.03-2.18,0.05-3.72) when comparing with those having 1298AA genotype. Patients with MSI⁺ gastric cancer had an increased frequency of the MTHFR 677TT genotype when comparing with those suffering from MSI^- gastric cancer (P=0.009) and with controlled subjects (P=0.008). There was no significant association found between MTHFR A1298C polymorphism and MSI(P＞0.05). Conclusion Polymorphism of MTHFR C677T was associated with increased risk on gastric corpus cancer and reduced risk on gastric cardia cancer. The polymorphism of MTHFR A1298C was associated with reduced risk for gastric antrum cancer while MSI pathway was possibly involved in the development of gastric cancer with MTHFR 677TT genotype.

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