亚甲基四氢叶酸还原酶基因多态性与结直肠癌易感性的关系

目的：研究亚甲基四氢叶酸还原酶（methylenetetrahydrofolate reductase,MTHFR）基因C677T、A1298C多态性与结直肠癌易感性的关系.方法：在江苏省进行了一个病例-对照研究（结直肠癌患者315例,人群对照371例）,调查研究对象的生活习惯,抽取静脉血,提取白细胞DNA,采用PCR-RFLP检测研究对象的MTHFR C677T、A1298C基因型.结果：1）男女合计的结直肠癌组、结肠癌组和直肠癌组与对照组之间的MTHFR C677T、A1298C基因型分布频度和等位基因频度差异无统计学意义,MTHFR C677T、A1298C基因多态与结直肠癌、结肠癌和直肠癌的易感性无显著相关.2）在男性中,结肠癌组MTHFR C677T T/T基因型的频度为24.6%,明显高于对照组的14.8%,但差异无统计学意义,X2=3.42,P=0.064.与C677T C等位基因携带者相比,T/T基因型者发生结肠癌的危险性显著升高,其性别、年龄、居住地区及吸烟、饮酒和饮茶习惯调整后的OR为2.15（95%CI：1.07～4.33）.与同时携带MTHFR C677T C等位基因和A1298C A/A基因型者相比,男性的MTHFR C677T T/T和A1298C A/A基因型携带者发生结肠癌的危险性显著升高,其调整OR为2.64（95%CI：1.20～5.81）,而他们发生直肠癌的危险性则明显降低,（调整OR=0.47,95%CI：0.22～1.03）.结论：MTHFR C677T基因多态可以影响男性结、直肠癌的易感性,MTHFR A1298C多态与C677T多态在对男性结、直肠癌易感性的影响中有协同作用.     

MTHFR基因多态和饮酒习惯与结直肠癌易感相关性的研究

目的:探讨亚甲基四氢叶酸还原酶(MTHFR)与结直肠癌(CRC)风险的关系。方法:进行了以医院为基础的结直肠癌病例对照研究(结直肠癌新发病例300例,对照300例)。对叶酸代谢相关基因MTHFRC677T和A1298C多态性进行了检测,并与结直肠癌风险关联进行了分析。结果:未观察到MTH-FR677和1298多态单独对CRC发生的影响,但发现MTHFR-677CT/1298AC组合型发生结直肠癌的风险增加,OR值为2.32(95%CI,1.10～4.92,P=0.027)。未发现MTHFR单倍型和双体型基因与CRC的风险之间存在统计学的显著关联。MTHFRC677T和A1298C基因与吸烟程度之间存在交互作用(似然比检验,P=0.002,P=0.001),在吸烟<16包年者中,MTHFR-677T等位基因患结直肠癌的风险增加2.09(95%CI,1.07～4.04),而在吸烟≥16包年者中,MTHFR-1298AA基因型患结直肠癌的风险明显下降,OR值为0.37(95%CI,0.17～0.80)。MTHFRC677T多态与饮酒之间存在交互作用(似然比检验,P=0.000)。结论:MTHFR-677CT/1298AC组合型基因是CRC的危险因素,MTHFR与吸烟、饮酒之间存在一定的交互作用。     

亚甲基四氢叶酸还原酶基因多态性与中国人群食管癌易感性的Meta分析

目的运用Meta分析的方法综合评价中国人群中亚甲基四氢叶酸还原酶（MTHFR）基因多态性与食管癌发病的相关性。方法通过计算机文献检索中国生物医学文献数据库(CBM) 和PubMed数据库,并结合文献追溯、网上查询(www.baidu.com; www.google.cn)的方法,收集所有关于MTHFR基因多态性与食管癌易感性的病例对照研究或队列研究。以食管癌组与对照组人群基因型分布的OR值为效应指标,各资料间进行一致性检验,以确定采用固定或随机效应模型进行合并分析。发表偏倚用漏斗图和Egger’s线性回归检验来评估。结果共有在国内外发表的相关文献10篇纳入分析,Meta分析结果表明：MTHFR C677T基因多态和MTHFR A1298C基因多态合并OR值及其95%CI分别为1.97（1.69,2.30）,0.84(0.66,1.08)。按是否吸烟进行分层发现吸烟组中MTHFR 677CT/TT基因型与食管癌有关(OR=2.57,95%CI:1.73~3.80),而不吸烟组中未见MTHFR 677CT/TT基因型与食管癌存在关联（OR=1.33,95%CI:0.94~1.88)。结论中国人群MTHFR C677T基因多态性与食管癌易感性有关,MTHFR A1298C基因多态性与食管癌易感性无统计学关联。吸烟可能会增加MTHFR C677T基因型个体患食管癌的危险性。     

乙醇和乙醛脱氢酶基因多态与男性结直肠癌的易感性

目的研究乙醇脱氢酶2(ADH2)和乙醛脱氢酶2(ALDH2)基因多态及饮酒习惯与男性结直肠癌易感性的关系。方法在江苏省进行了一项病例-对照研究(结直肠癌患者190例,人群对照222名),调查研究对象的生活习惯,抽取静脉血,提取白细胞DNA,采用聚合酶链反应(PCR)和变性高效液相色谱法(DHPLC)检测研究对象的ADH2Arg47His(G-A)和ALDH2Glu487Lys(G-A)的基因型。结果①ADH2A/A和ALDH2G/G基因型显著增加结直肠癌的易感性。在调整了年龄和吸烟状况后,ADH2A/A基因型者与携带G等位基因者相比,发生结直肠癌的危险性上升到1.61(95%CI:1.09~2.38);ALDH2G/G基因型者与携带A等位基因者相比,发生结直肠癌的危险性上升到1.79(95%CI:1.19~2.69)。②与ADH2G和ALDH2A等位基因携带者相比,同时携带ADH2A/A和ALDH2G/G基因型者发生结直肠癌的OR值上升到3.05(95%CI:1.67~5.57);与不饮酒的ADH2G等位基因携带者相比,拥有ADH2A/A基因型的饮酒者的OR值上升到3.44(95%CI:1.84~6.42);与不饮酒的ALDH2A等位基因携带者相比,拥有AL-DH2G/G基因型的饮酒者的OR值上升到2.70(95%CI:1.57~4.66)。结论ADH2和ALDH2基因多态性与男性结直肠癌的易感性相关。ADH2,ALDH2基因多态之间以及基因多态与饮酒习惯之间,在结直肠癌发生中存在显著的协同作用。     

亚甲基四氢叶酸还原酶基因多态性与非小细胞肺癌化疗敏感性的关系

背景与目的 亚甲基四氢叶酸还原酶（MTHFR）是叶酸代谢的关键酶，在DNA甲基化中起重要作用。体外研究已经证明一些基因的异常甲基化可以影响肿瘤细胞对细胞毒性药物和干扰DNA合成药物的敏感性。本研究旨在观察MTHFR基因C677T、A1298C多态与非小细胞肺癌（NSCLC）患者对铂类药物为基础的化疗方案敏感性的关系。方法 收集经病理学确诊的中、晚期NSCLC病例97例。用PCR—RFLP技术检测患者MTHFR基因型。所有患者均经以铂类为基础的化疗方案治疗。结果 ①97例NSCLC病例中，MTHFRC677TC／C、C／T和T／T基因型频度分别为34．0％、50．5％和15．5％，A1298CA／A、A／C和C／C基因型频度分别为64．6％、29．2％和6．2％。化疗后总有效率（完全缓解＋部分缓解）为39．2％。②分别分析MTHFRC677T多态性和A1298C多态性与化疗疗效的关系时，未发现这两个多态与NSCLC化疗的疗效有明显关系。而联合分析MTHFRC677T多态性A1298C多态基因型与化疗疗效的关系时，发现携带MTHFRC677TT等位基因（C／T或T／T基因型）、同时携带A1298CA／A基因型者的有效率为51．1％，显著高于同时携带C677TC／T基因型及A1298CC等位基因者（12．5％）（P=0．007，OR=7．30，95％CI：1．34～52．47）。结论 MTHFR基因C677T和A1298C多态联合作用可影响NSCLC对化疗的敏感性，MTHFR基因型检测对指导NSCLC的化疗、预测疗效具有较高的临床价值。     

生长激素1基因多态性和烟酒习惯与结直肠癌易感性的关系

目的:研究生长激素1(growth hormone1,GH1)基因T1663A多态性与结直肠癌易感性的关系。方法:在江苏省进行了一个病例-对照研究(结直肠癌患者315例,人群对照439名),调查研究对象的生活习惯,抽取静脉血,提取白细胞DNA,采用PCR-RFLP检测研究对象的GH1T1663A基因型。结果:1)GH1T/T、T/A和A/A基因型分布频度在结直肠癌组分别为42.2%、46.7%和11.1%,对照组分别为38·1%、45·9%和16·0%,两组差异无统计学意义,χ2MH=3·907,P=0·142。但在调整性别、年龄、吸烟和饮酒习惯后,A/A基因型者与T/T基因型者相比,发生结直肠癌的危险性显著降低(OR=0·88,95%CI:0·78~0·99,P=0·0287)。2)多因素分析结果显示,饮酒者患结直肠癌的危险性显著增高(OR=1·96,95%CI:1·34~2·86,P=0·0005),A/A基因型与降低结直肠癌的危险性有关,而吸烟与增加或降低结直肠癌的危险性无显著相关。3)GH1基因多态与吸烟、饮酒相互作用的分层分析发现,在不吸烟者中,GH1A/A基因型者与T等位基因型者相比,发生结直肠癌的危险性显著降低(性别和年龄调整OR=0·50,95%CI:0·27~0·93);在不饮酒者中,GH1A/A基因型者发生结直肠癌的调整OR为0·56(95%CI:0·32~0·99)。结论:T1663A GH1基因的A/A基因型可降低结直肠癌易感性,特别是在不吸烟和不饮酒者中。     

叶酸代谢酶基因多态与结直肠癌易感性的关系

目的 研究叶酸代谢酶基因多态MTHFRC677T、MTHFRA1298C、MTRA2756G和MTRRA66G及其联合作用与结直肠癌（CRC）易感性的关系。方法 采用聚合酶链-限制性片段长度多态性方法,检测140例CRC患者和343例正常对照者的叶酸代谢酶基因多态,采用非条件Logistic回归模型和似然比检验,分析各多态及其联合作用与CRC的关系。结果 MTR2756G等位基因携带者患CRC的风险是野生型纯合子（AA）的2倍（95％Cl为1．22～3．40）。与同时是MTHFR1298AA和MTR2756AA基因型者相比,同时是MTHFR1298AA和MTR2756AG／GG基因型者患CRC的风险显著升高（OR=2．57,95％C／为1．42～4．65）,两者之间存在联合作用（P=0．04）。结论 MTR2756G等位基因可能是CRC的危险因素,MTHFRA1298C和MTRA2756G之间存在联合作用。     

MTHFR C677T基因型、烟酒嗜好及其相互作用与胃癌

目的研究亚甲基四氢叶酸还原酶(MTHFR)基因C677T多态性及其和烟酒茶嗜好相互作用与胃癌易感性的关系.方法在上消化道癌高发区淮安市进行了一个病例-对照研究(胃癌107例,人群对照200例),调查研究对象的生活习惯,采用PCR-RFLP技术检测研究对象的MTHFR基因型.结果①胃癌组中MTHFR变异型等位基因携带者的比例为79.4%,显著高于对照组的68.5%(x2=4.15,P=0.0416).MTHFR变异型等位基因携带者发生胃癌的危险性显著升高(OR=1.78,95%CI0.99～3.22;性别、年龄吸烟和饮酒习惯调整OR=1.79,95%CI1.01～3.19).②与携带MTHFR野生基因型的不吸烟者相比,携带变异型基因且伴有吸烟习惯者发生胃癌的OR为7.82(95%CI2.43～25.19),伴有经常饮酒的习惯者发生胃癌的OR为2.87(95%CI1.28～6.47).与不吸烟、不经常饮酒的野生型MTHFR基因携带者相比,伴有吸烟和经常饮酒习惯的变异型基因携带者发生胃癌的OR为8.67(95%CI2.12～40.94).结论MTHFRC677T变异型基因型与胃癌的易感性有关;吸烟和饮酒与MTHFR变异基因型在胃癌发生中有明显的协同作用.调查生活习惯同时检测MTHFR基因型有助于胃癌高危人群和个体的筛选.     

MTHFR基因1298 A→C多态与新疆哈萨克族食管癌风险关系的研究

目的:探讨亚甲基四氢叶酸还原酶(MTHFR)基因1298A→C多态及其和生活习惯相互作用与新疆哈萨克族食管癌风险的关系。方法:收集经组织病理学确诊的哈萨克族食管鳞癌新发病例88例外周血液标本,提取DNA;72名健康哈萨克族人群作为对照,同时调查每个研究对象的吸烟、饮酒情况。用PCR-RFLP技术检测研究对象的MTHFR1298A→C基因多态性。结果:病例组MTHFR1298AA、AC和CC基因型分别为63.64%、34.09%和2.27%,与对照组的72.22%、27.78%和0相比差异无统计学意义,χ2MH=2.57,P=0.276。MTHFR1298AA、MTHFR1298AC基因型与哈萨克族食管癌的发生无显著相关性,P>0.05。病例组与对照组1298C等位基因频率分别为0.19和0.14,两组间差异无统计学意义,P>0.05。与携带MTH-FR1298AA基因型的不吸烟者相比,携带MTH-FR1298C等位基因且有吸烟习惯者的性别、年龄以及饮酒习惯调整OR值为2.353(95%CI为0.892～6.210)。与携带MTHFR1298AA基因型的不饮酒或不常饮酒者相比,携带MTHFR1298C等位基因并伴有经常饮酒的习惯者发生食管癌的危险性也显著增高,其性别、年龄以及饮酒习惯调整OR值为1.860(95%CI为0.585～5.915)。结论:叶酸摄入不足是新疆哈萨克族食管癌的危险因素;MTHFR1298AC和CC基因型对吸烟、饮酒习惯增加食管癌发生风险作用有放大效应。     

亚甲基四氢叶酸还原酶基因C677T多态性、生活习惯与贲门癌易感性的关系

[目的]研究亚甲基四氢叶酸还原酶(MTHFR)基因C677T多态性及其与烟酒茶嗜好相互作用与贲门癌易感性的关系.[方法]在上消化道癌高发区淮安市进行了病例-对照研究(贲门癌89例,对照人群223例),调查研究对象的生活习惯,采用PCR-RFLP技术检测研究对象的MTHFR基因型.应用SAS软件或EPI Info软件进行统计学分析.[结果]①男性吸烟者和女性饮酒者与男性不吸烟者和女性不饮酒者相比患贲门癌的风险增高;不饮茶者与饮茶者相比发生贲门癌的危险性升高.②贲门癌组中MTHFRC/T T/T基因型携带者占82.0%,显著高于对照组的70.3%.与携带MTHFRC/C基因型相比,C/T T/T基因型携带者发生贲门癌的危险性(OR)为2.12(95%CI 1.14～3.95),调整性别、年龄、吸烟、饮酒、饮茶及生蔬菜、水果、肉和豆制品摄取习惯后OR为2.05(95%CI 1.05～2.03).③在吸烟、每周饮酒≥2次和不饮茶者中,携带MTHFRC/T T/T基因型者发生贲门癌的危险性显著上升.[结论]MTHFR基因型与贲门癌的易感性有关;MTHFR基因多态性影响吸烟、饮酒和饮茶与贲门癌之间的关系.     

Genetic polymorphisms of methylenetetrahydrofolate reductase and susceptibility to colorectal cancer

Objectives: To study the relation between genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) C677T or A1298C and the susceptibility of colorectal cancer. Methods: We conducted a case-control study with 315 cases of colorectal cancer and 371 population-based controls in Jiangsu province, China. The epidemiological data were collected, and DNA of peripheral blood leukocytes was obtained from all of the subjects. MTHFR C677T and A1298C genotypes were detected by the PCR-RFLP method. Results: (1) When men and women were assessed together, the frequencies of the MTHFR C677T and A1298 genotypes or their alleles were not significantly different between controls and colon cancer or rectal cancer cases. No significant relation was observed between MTHFR C677T or A1298C polymorphisms and colon or rectal cancer susceptibility. (2) Among males, individuals who had MTHFR C677T T/T genotype were at a significantly higher risk of developing colon cancer (age-, residence-, smoking-, alcohol drinking-, tea consumption-adjusted OR=2.15, 95%CI: 1.07-4.33) compared with those who had C677T C allele. Individuals who had C677T T/T and A1298C A/A genotypes were at an increased risk of developing colon cancer (adjusted OR=2.64, 95%CI: 1.20-5.81) compared with those with C677T C allele and A1298C A/A genotypes among males. On the contrary, individuals who had C677T T/T and A1298C A/A genotypes were at an decreased risk of developing rectal cancer (adjusted OR=0.47, 95%CI: 0.22-1.03). Conclusions: These results in the present study suggested that polymorphisms of the MTHFR C677T could influence susceptibility to colon or rectal cancer and that there was a coordinated effect between MTHFR A1298C A/A and C677T T/T genotypes among males.     

Diets, polymorphisms of methylenetetrahydrofolate reductase, and the susceptibility of colon cancer and rectal cancer

The aim of this study was to investigate the association of environmental factors (dietary folate, methionine and drinking status) and polymorphisms in the methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) gene, as well as the combination of these factors, with the risk of colon cancer and rectal cancer. A case-control study of 53 colon cancer patients, 73 rectal cancer patients and 343 healthy controls was conducted. Genotypes of C677T and A1298C polymorphisms were analyzed by PCR-RFLP. The dietary folate and methionine intakes were assessed using food-frequency questionnaires and food consumption tables. Unconditional logistic regression was applied to estimate the odds ratios (ORs) and their 95% confidence intervals (CIs). The frequency of MTHFR 677T and 1298C alleles in healthy population were 39.4 and 17.2%, respectively. After adjustment for specific variants, the MTHFR 677TT genotype showed a significantly reduced risk of colon cancer compared with the wild type (OR=0.22, 95% CI: 0.50-0.98), and 1298C allele-carrier showed an inverse association with the risk of rectal cancer compared to the wild type (OR=0.52, 95% CI: 0.28-0.98). Adequate intake of folate was a protective factor from colon cancer (OR=0.32, 95% CI: 0.12-0.88) and MTHFR C677T polymorphism showed a statistically significant effect (OR=0.25, 95% CI: 0.06-0.93), reducing the risk of colon cancer in groups that have an intake of folate exceeding 115.64ng per 1000kcal per day. This study suggests that MTHFR C677T and A1298C polymorphisms are associated with the reduced risk of colon and rectal cancers, respectively. Adequate folate intake shows an inverse association with the risk of colon cancer. There is a significant interaction between MTHFR C677T polymorphism and folate intake in reducing the risk of colon cancer.     

Polymorphisms in the MTHFR gene are associated with breast cancer.

The methylenetetrahydrofolate reductase (MTHFR) gene is a polymorphic gene involved in folate metabolism, DNA biosynthesis, methylation and genomic integrity in actively dividing cells. The MTHFR C677T and A1298C polymorphisms are likely to play an important role in the susceptibility to breast cancer. In this case-control study, we examined the role of MTHFR C677T and A1298C polymorphisms in breast cancer patients. We genotyped 118 premenopausal women with sporadic breast cancer and 193 controls, using a PCR-RFLP method. The allele frequencies of the MTHFR 677T were 31.36% in the breast cancer cases and 28.76% in the controls. The allele frequencies of the MTHFR 1298C were 37.29% in the breast cancer subjects and 31.35% in the controls. Frequencies of MTHFR C677C, C677T and T677T were 50.8, 33.9 and 14.4% in the breast cancer patients and 48.7, 45.1 and 6.2% in the controls, respectively. The results of a chi(2) analysis indicated that the MTHFR 677T allele was significantly distributed (chi(2) = 7.234; p = 0.027). Likewise, the MTHFR T677T genotype showed a 2.5-fold increased risk for breast cancer and the C1298C genotype showed a 1.9-fold increased risk for breast cancer. In the compound genotypes, T677T/A1298A and C677C/C1298C showed a 4.472- and a 2.301-fold increased risk for breast cancer (OR = 4.472, p = 0.001, and OR = 2.301, p = 0.024), respectively. In conclusion, our data suggest that the MTHFR 677T, 1298C alleles, T677T, C1298C genotypes, and C677C/C1298C and T677T/A1298A compound genotypes are genetic risk factors for premenopausal women with sporadic breast cancer.     

MTHFR C677T and A1298C polymorphisms: diet, estrogen, and risk of colon cancer.

5,10-methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate metabolism, diverting metabolites toward methylation reactions or nucleotide synthesis. Using data from an incident case-control study (1608 cases and 1972 controls) we investigated two polymorphisms in the MTHFR gene, C677T and A1298C, and their associations with risk of colon cancer. All of the combined genotypes were evaluated separately, and the 1298AA/677CC (wild-type/wild-type) group was considered the reference group. Among both men and women, the 677TT/1298AA (variant/wild-type) genotype was associated with a small reduction in risk [men: odds ratio (OR), 0.7, 95% confidence interval (CI), 0.5-1.0; women: OR, 0.8, 95% CI, 0.5-1.2]. However, the 677CC/1298CC (wild-type/variant) genotype was associated with a statistically significant lower risk among women (OR, 0.6; 95% CI, 0.4-0.9) but not men. When the polymorphisms were considered individually, for A1298C a significant risk reduction associated with the homozygous variant CC genotype was seen among women only (OR, 0.6; 95% CI, 0.5-0.9), and nonstatistically significant reduced risks were observed for the variant 677 TT genotypes among both men and women. Stratification by nutrient intakes showed inverse associations with higher intakes of folate, vitamin B(2), B(6), B(12), and methionine among women with the MTHFR 677CC/1298AA genotypes, but not those with 677TT/1298AA. We observed opposite risk trends for both MTHFR variants, depending on whether women used hormone-replacement therapy or not (P for interaction = <.01). In summary, this study supports recent findings that the MTHFR A1298C polymorphism may be a predictor of colon cancer risk and have functional relevance. The possible interaction with hormone-replacement therapy warrants additional investigation.     

Genetic polymorphisms of the methylenetetrahydrofolate reductase gene, plasma folate levels and breast cancer susceptibility: a case-control study in Taiwan

Methylenetetrahydrofolate reductase (MTHFR) balances the pool of folate coenzymes in one-carbon metabolism for DNA synthesis and methylation, both are implicated in carcinogenesis. Two common variants in the MTHFR gene (C677T and A1298C) have been associated with reduced enzyme activity, thereby making MTHFR polymorphisms a potential candidate cancer-predisposing factor. To evaluate the C677T and A1298C functional polymorphisms in the MTHFR gene and their associations with breast cancer risk, as well as the potential modifying effect by plasma folate status on the MTHFR-associated risk, a hospital-based case-control study was conducted on a Taiwanese population consisting of 146 histologically confirmed incident breast cancer cases and their 285 age-matched controls without a history of cancer. A PCR-RFLP method was used for MTHFR polymorphism genotyping and RIA was used to measure the plasma folate. Statistical evaluations were performed using logistic regression analysis. The plasma folate level was inversely associated with breast cancer risk with an adjusted odds ratio (OR) of 0.52 [95% confidence interval (CI): 0.26-1.05] observed among women who were in the highest plasma folate tertile. The MTHFR 677T and 1298C variant alleles were associated with decreased risk for breast cancer [adjusted ORs were 0.81 (95% CI: 0.54-1.21) and 0.57 (95% CI: 0.36-0.89) for 677CT + TT genotypes and 1298AC + CC genotypes, respectively]. Furthermore, compound heterozygote and homozygote variants (677CT + TT and 1298AC + CC) had greater reduced risk (adjusted OR: 0.11, 95% CI: 0.03-0.43) among women with lower plasma folate levels. These results provide support for the important role of folate metabolism in breast tumorigenesis. Further mechanistic studies are warranted to investigate how MTHFR combined genotypes exert their effect on cancer susceptibility.     

Allele and Genotype Frequencies of the Polymorphic Methylenetetrahydrofolate Reductase and Lung Cancer in ther Jordanian Population: a Case Control Study

Background: Methylenetetrahydrofolate reductase (MTHFR) is involved in amino acid synthesis and DNAfunction. Two common polymorphisms are reported, C677T and A1298C, that are implicated in a number ofhuman diseases, including cancer. Objective: The association between MTHFR C677T and A1298C genotype andhaplotype frequencies in risk for lung cancer (LC) was investigated in the Jordanian population. Materials andMethods: A total of 98 LC cases were studied for MTHFR C677T and A1298C polymorphisms, compared to 89controls taken from the general population, employing the PCR-RFLP technique. Results: The frequency of thegenotypes of MTHFR C677T among Jordanians was: CC, 59.6%, CT, 33%; and TT, 7.4% among LC cases and49.4%, 40.2% and 10.3% among controls. No significant association was detected between genetic polymorphismat this site and LC. At MTHFR A12987C, the genotype distribution was AA, 29.5%; AC, 45.3%, and CC 25.3%among LC cases and 36.8%, 50.6% and 12.6% among controls. Carriers of the CC genotype were more likelyto have LC (OR=2.5; 95%CI: 1.04-6; p=0.039) as compared to AA carriers. Smokers and males with the CCgenotype were 9.9 and 6.7 times more likely to have LC, respectively (ORsmokers=9.9; 95%CI: 1.2-84.5, p=0.018;ORmen=6.6; 95%CI: 1.7-26.2, p=0.005). Haplotype analysis of MTHFR polymorphism at the two loci showeddifferential distribution of the CC haplotype (677C-1298C) between cases and controls. The CC haplotypewas associated with an increased risk for lung cancer (OR=1.6; 95% CI: 1.03-2.4, p=0.037). Conclusions: Thegenetic polymorphism of MTHFR at 1298 and the CC haplotype (risk is apparently lower with the C allele atposition 677) may modulate the risk for LC development among the Jordanian population. Risk associated withthe 1298C allele is increased in smokers and in males. The results indicate that a critical gene involved in folatemetabolism plays a modifying role in lung cancer risk, at least in the Jordanian population.     

Associations between 5,10-methylenetetrahydrofolate reductase codon 677 and 1298 genetic polymorphisms and environmental factors with reference to susceptibility to colorectal cancer: a case-control study in an Indian population

Although the incidence rate of colorectal cancer is very low, and rectal cancer remains more common in India, a significant increase in its incidence has been reported for both men and women over the last 2 decades. We evaluated MTHFR genetic susceptibility and common environmental risk factors in the development of colon and rectal cancer, and assessed the interactions between gene and environmental factors with colorectal cancer in a case-control study in the Indian population. The study included 59 colon cancer cases, 243 rectal cancer cases and 291 controls. The variant MTHFR 677T allele is rare, while the 1298C allele is common among Indians. MTHFR 677T showed no association with colon cancer (OR = 0.82; 95% CI 0.28-2.05) and a nonstatistically significantly elevated risk with rectal cancer (OR = 1.51; 95% CI 0.86-2.68), and MTHFR 1298 CC genotype was found to be associated with a significantly decreased risk for both colon cancer (OR = 0.30, 95% CI 0.09-0.81) and rectal cancer (OR = 0.43, 95% CI 0.23-0.80). High intake of nonfried vegetables or fruits was inversely associated with both colon and rectal cancer risk. Especially, the combination of a high intake of nonfried vegetables and MTHFR 1298CC genotype was associated with the lowest rectal cancer risk (OR = 0.22, 95% CI 0.09-0.52). Regarding alcohol consumption, indigenous Indian alcohol drinkers (OR = 2.26, 95% CI 0.86-6.36), and those consuming alcohol for duration more than 20 years (OR = 1.55, 95% CI 0.73-3.33), were at a somewhat higher rectal cancer risk. Moreover, the consumed alcohol amount (gram-years) may be also associated with colon or rectal cancer risk.     

Risk Factors for Rectal Cancer and Methylenetetrahydrofolate Reductase Polymorphisms in a Population in Northeast Thailand

Background and Aim: Polymorphisms in methylenetetrahydrofolate reductase (MTHFR) are known to beassociated with predisposition for certain cancers. This study aimed to evaluate the effects of lifestyle factors,family history and genetic polymorphisms in MTHFR C677T and A1298C on rectal cancer risk and possibleinteractions with lifestyle factors in Northeast Thailand. Methods: A hospital-based case-control study wasconducted during 2002-2006 with recruitment of 112 rectal cancer cases and 242 non-rectal cancer patient controls.Information was collected using a structured-questionnaire. Blood samples were obtained for assay of MTHFRC677T and A1298C genotypes by polymerase chain reaction with restriction fragment length polymorphism(PCR-RFLP) techniques. Associations between lifestyle factors, family history and genetic polymorphisms v.s.rectal cancer risk were assessed using logistic regression analysis. Results: Subjects with frequent and occasionalconstipation had a higher risk (OR_adj.=14.64; 95%CI=4.28-50.04 and OR_adj.=2.15; 95%CI=1.14-4.06), along withthose who reported ever having hemorrhoids (OR_adj.=2.82; 95%CI=1.36-5.84) or a family history of cancer(OR_adj.=1.90; 95%CI=1.06-3.39). Consumption of a high level of pork was also associated with risk (OR_adj.=1.82;95%CI=1.05-3.15). Interactions were not observed between MTHFR and other risk factors. Conclusions: Thisstudy suggested that the risk factors for rectal cancer in the Thai population are bowel habits, having hadhemorrhoids, a family history of cancer and pork consumption.     

MTHFR gene polymorphisms and bladder cancer susceptibility: a meta-analysis including race, smoking status and tumour stage

Epidemiological studies have investigated that functional polymorphisms in the methylene-tetrahydrofolate reductase (MTHFR) gene may play an essential role in bladder carcinogenesis, but the numerous published studies have reported inconclusive results. The objective of the current study was to conduct an updated analysis in order to investigate the association between polymorphisms in the MTHFR gene and risk of bladder cancer. We searched the Pubmed database for all articles published up to March 31, 2011 that addressed bladder cancer and polymorphisms and variants or mutations of MTHFR for analysis using statistical software. Results for two polymorphisms (C677T and A1298C) in 27 case-control were studies from 15 articles indicated individuals carrying the 677T allele (TC or TT+TC) to have a reduction to a 29% or 21% compared to the wild genotype (CC) in mixed populations (OR: 0.71, 95%CI: 0.55-0.93 or OR: 0.79, 95%CI: 0.64-0.97, respectively) and it is shown that there is significant positive associations between A1298C polymorphism and bladder cancer in Africans (OR: 1.24, 95%CI: 1.02-1.52 for C vs.A; OR: 1.35, 95%CI: 1.10-1.66 for CA vs. AA; OR: 1.29, 95%CI: 1.08-1.55 for CC+CA vs. AA). However, no significant relationship was found in two polymorphisms in the stratified analysis by smoking status. Interestingly, individuals carrying the 677T allele (TT+TC) demonstrated a higher percentage of invasive than superficial cases (OR: 1.38, 95%CI: 1.13-1.69). The results from the current update analysis suggest that C677T and A1298C polymorphisms in the MTHFR gene are associated with bladder cancer risk and prognosis. Further evaluation based on more studies with larger groups of patients are now required.