亚甲基四氢叶酸还原酶和胸苷酸合成酶基因多态与乳腺癌化疗敏感性关系的研究

目的：观察亚甲基四氢叶酸还原酶（MTHFR）基因C677T、A1298C多态和胸苷酸合成酶（TS）基因5′-UTR（28bp）、3′-UTR（6bp）多态与乳腺癌患者对化疗敏感性的关系。方法：乳腺癌患者87例，其中新辅助化疗61例，晚期姑息化疗26例。分别接受CAF、AT方案化疗。所有病例化疗前抽静脉血，提取白细胞DNA，用PCR-RFLP技术检测分析MTHFR和TS基因型。结果：87例乳腺癌患者化疗总有效率为69．0％。39例接受CAF方案化疗患者有效率为61．5％，48例接受AT方案化疗患者的有效率为75．0％。MTHFR C677T T／T基因型患者的化疗有效率（87．5％）显著高于C／C基因型患者（52．4％），χ^2=6．24，P=0．01。CAF方案化疗组患者中，MTHFR C677T T／T、T／C基因型患者的化疗有效率（90．0％、68．8％）显著高于C／C基因型患者（30．8％），χ^2=8．74，P=0．011。61例新辅助化疗患者，MTHFR C677TT／T基因型患者的化疗病理反应率（83．3％）显著高于C／C基因患者（35．7％），χ^2=7．619，P=0．006。TS6bp-6／-6基因型患者的化疗病理反应率（80．8％）显著高于-6／＋6基因患者（46．7％），χ^2=6．911，P=0．009。接受AT方案化疗的患者中TS-6／-6基因型患者的化疗病理反应率（92．9％）显著高于-6／＋6基因型患者（45．5％），χ^2=6．866，P=0．009。结论：MTHFR C677T和TS6bp基因多态性对指导乳腺癌临床个体化治疗具有较高的应用价值。     

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。     

亚甲基四氢叶酸还原酶基因C677T和A1298 C多态性与消化道癌化疗敏感性关系的研究

目的：亚甲基四氢叶酸还原酶（methylenetetrahydmfolatere ductase,MTHFR）基因变异影响MTHFR的活性,以致影响体内5,10-MTHF的浓度,从而影响氟尿嘧啶（5-FU）的抗瘤活性。本研究旨在观察MTHFR基因C677T、A1298C多态性对预测消化道癌患者对5-FU的敏感性和化疗毒性的临床价值。方法：收集经病理学检查确诊的晚期消化道癌122例。所有病例化疗前抽外周静脉血2毫升,用PCR-RFLP技术检测研究对象的MTHFR基因型。C677T基因型分为野生型纯合子（C／C）、杂合子（C／T）、变异型纯合子（T／T）三种类型,A1298C基因型分为纯合子A／A、杂合子A／C和纯合子C／C三种类型。所有患者经含5-FU为基础的联合化疗方案化疗。结果：122例晚期消化道癌患者中,化疗总有效率为38．5％,其中C677TT／T基因型患者的化疗有效率为82．1％,显著高于C／C基因型患者的21．6％（X^2=23．402;P=0．000）,C／T基因型患者的28．1％（X^2=22．110;P=0．000）,C／C基因型与C／T基因型之间无差异（X^2=0．491;P=0．481）。A1298CA／A基因型患者的化疗有效率为45．3％,显著高于A／C基因型患者的22．9％（X^2=5．297;P=0．021）。在不同化疗方案亚组分析中,经CFL方案、CFH方案和L-FP方案化疗的C677TT／T基因型患者有效率显著高于C／T、C／C基因型患者（X^2=8．156,df=2,P=0．017;X^2=15．297,df=2,P=0．000;X^2。=6．685,df=2,P=0．036）;A1298CA／A基因型患者的疗效均高于A／C＋C／C基因型患者,但仅CFL方案组取得统计学差异（X^2=5．400;df=1,P=0．020）。C677TT／T基因型患者的恶心呕吐和口腔炎副反应均显著高于C／C、C／T基因型。A1298CA／A基因型患者的毒副反应均显著高于C／C＋A／C基因患者。结论：MTHFR基因C677T、A1298C基因型多态性对于预测以5-FU为基础化疗方案治疗晚期消化道癌的疗效和毒性具有较好的临床意义。     

亚甲基四氢叶酸还原酶和胸苷酸合成酶基因多态与乳腺癌化疗敏感性关系的研究

目的:观察亚甲基四氢叶酸还原酶(MTHFR)基因C677T、A1298C多态和胸苷酸合成酶(TS) 基因5'-UTR(28 bp)、3'-UTR(6 bp)多态与乳腺癌患者对化疗敏感性的关系.方法:乳腺癌患者87例,其中新辅助化疗61例,晚期姑息化疗26例.分别接受CAF、AT方案化疗.所有病例化疗前抽静脉血,提取白细胞DNA,用PCR-RFLP技术检测分析MTHFR和TS基因型.结果:87例乳腺癌患者化疗总有效率为69.0%.39例接受CAF方案化疗患者有效率为61.5%,48例接受AT方案化疗患者的有效率为75.0%.MTHFR C677T T/T基因型患者的化疗有效率(87.5%)显著高于C/C基因型患者(52.4%),χ2＝6.24,P＝0.01.CAF方案化疗组患者中,MTHFR C677T T/T、T/C基因型患者的化疗有效率(90.0%、68.8%)显著高于C/C基因型患者(30.8%),χ2＝8.74,P＝0.011.61例新辅助化疗患者,MTHFR C677T T/T基因型患者的化疗病理反应率(83.3%)显著高于C/C基因患者(35.7%),χ2＝7.619,P＝0.006.TS 6 bp -6/-6基因型患者的化疗病理反应率(80.8%)显著高于-6/ 6基因患者(46.7%),χ2＝6.911,P＝0.009.接受AT方案化疗的患者中TS -6/-6基因型患者的化疗病理反应率(92.9%)显著高于-6/ 6基因型患者(45.5%),χ2＝6.866,P＝0.009.结论:MTHFR C677T和TS 6 bp基因多态性对指导乳腺癌临床个体化治疗具有较高的应用价值.     

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 C677T基因多态对胃癌辅助化疗预后的影响

[目的]研究亚甲基四氢叶酸还原酶基因（MTHFR）C677T多态对接受氟尿嘧啶（5-Fu）为基础辅助化疗胃癌患者预后的影响。[方法]确诊的胃癌患者110例，采用5-Fu为基础的方案进行辅助化疗。采用聚合酶链反应-连接酶检测反应技术检测MTHFR C677T基因多态。[结果]110例胃癌患者中，MTHFR 677 T／T、C/T和C／C基因型频率分别为19．1％（21／110）、47．3％（52，110）和33．6％（37／110）。110例患者复发率和死亡率分别为54．5％（60／110）和42．7％（47／110）。携带C／C基因型患者无复发生存率和总生存率均显著低于携带T/T或C/T基因型患者（P〈0．05）。Cox多因素分析显示，MTHFR C/C基因型是影响患者复发和生存的独立危险因素（P〈0．05）。[结论]MTHFR C677T基因多态性是接受5-Fu为基础辅助化疗胃癌患者的独立预后因素。     

基因多态性与FOLFOX方案治疗胃肠癌敏感性的关系

目的研究MTHFR C677T和XRCC1 G28152A基因多态性与接受FOLFOX方案的胃肠癌患者化疗敏感性与毒副反应的关系。方法经FOLFOX方案化疗的进展期胃肠癌48例（22例有临床可观察肿瘤病灶）,化疗前抽外周静脉血2 mL,用PCR-RFLP技术检测研究对象的MTHFR C677T和XRCC1 G28152A基因型。化疗两周期后全面评价疗效及毒副反应,并随访观察进展情况。结果 （1）48例胃肠癌患者,MTHFR 677 C/C、C/T、T/T基因型分别为39.6%、37.5%及22.9%。XRCC1 28152 G/G、G/A、A/A基因型分别为52.1%、45.8%及2.1%。22例可观察肿瘤病灶者MTHFR 677 C/C、C/T、T/T基因型疾病控制率分别为14.2%、66.6%和100.0%,T/T基因型明显高于C/C型（P〈0.05）;XRCC1 28152 G/G、G/A＋A/A基因型疾病控制率分别为90.9%、36.4%,差异有统计学意义（P〈0.05）。（2）48例患者带有MTHFR677 C/C、C/T、T/T基因型的2年无复发生存率分别为21.1%、36.8%和72.7%,T/T基因型明显高于C/C型（P〈0.05）;XRCC1 28152 G/G、G/A＋A/A基因型2年无复发生存率分别为52.0%和21.7%,差异有统计学意义（P〈0.05）。（3）患者接受FOLFOX方案化疗后带有MTHFR 677 C/T、T/T患者恶心/呕吐的发生率（77.8%、81.8%）明显高于C/C基因型患者（26.3%）。XRCC1 28152 G/G、G/A＋A/A基因型恶心/呕吐分别为44.0%,78.3%,差异有统计学意义（P〈0.05）,其余毒副反应与基因型之间差异均无统计学意义（P〉0.05）。结论 MTHFR C677T和XRCC1 G28152A基因多态对胃肠癌接受FOLFOX方案化疗疗效与毒性有良好的提示作用。     

亚甲基四氢叶酸还原酶基因单核苷酸多态与乳腺癌风险

目的 内研究亚甲基四氢叶酸还原酶(MTHFR)基因单核苷酸多态与女性乳腺癌风险的关系。方法 以聚合酶链反应(PCR)和限制性片段长度多态性(RFLF)分析方法,检测了217例乳腺癌患者和218例配对的正常对照者MTHFR因C677T和A1298C基因型,并比较不同基因型与乳腺癌风险的关系。结果 677TT基因型频率在乳腺癌患者和正常对照中的分布差异有显著性(32．7％比24．8％,P=0．02)。携带MTHFR 677TT基因犁者与携带MTHFR 677CC基因型者比较,前者罹患乳腺癌的风险增加1,84倍(95％ C：1．09～3．14)。MTHFR 677CT基因型以及MTHFR A1298C多态与乳腺癌风险不相关。结论 MTHFR基因677C→T突变是女性乳腺癌的遗传易感因素。     

MTHFR多态性对晚期胃癌患者化疗作用的预测研究

目的:研究亚甲基四氢叶酸还原酶(MTHFR)基因C677T、A1298C多态与胃癌患者对5-FU为基础的化疗敏感性和毒性的关系。方法:晚期胃癌患者106例,用聚合酶链反应-限定性片段长度多态性(PCR-RFLP)技术检测白细胞DNAMTH-FR基因型。所有患者经5-FU为基础的化疗方案治疗。结果:1)在106例晚期胃癌患者中,MTHFRC677TCC、CT、TT基因型分别占31·1%、46·2%和22·6%;MTH-FRA1298CAA、AC、CC基因型者分别为69·8%、29·2%和0·9%;化疗总有效率35·8%。2)MTHFRC677TTT基因型携带者化疗有效率(83·3%)明显高于C677TCT(24·5%;P=0·000)和C677TCC(18·2%;P=0·000)。而MTHFRA1298CAA组有效率(43·2%)亦明显高于A1298CAC CC组(18·8%,P=0·009)。3)在CFL、CFH、LFP方案治疗的患者中,C677T变异子携带者对化疗敏感性更高。对A1298C多态性,患者接受CFL方案化疗时,1298AA纯合子携带者有效率高于1298CT/CC患者。4)MTHFRC677TTT、CT或A1298CAA多态性携带者化疗相关的恶心/呕吐发生率明显高于其他三种多态性者。结论:MTHFR基因多态性的检测可能是晚期胃癌患者接受5-FU为基础化疗疗效和毒副反应的良好预测指标。     

亚甲基四氢叶酸还原酶多态性与乳腺癌化疗敏感性的相关研究

目的:观察叶酸代谢的关键酶亚甲基四氢叶酸还原酶(MTHFR)基因C677T、A1298C多态性与乳腺癌FEC方案化疗敏感性的关系。方法:收集经病理学确诊的初治乳腺癌患者104例,所有病例化疗前抽静脉血,提取DNA,用PCR-RFLP技术检测MTHFR基因型,所有患者行FEC方案新辅助或姑息性化疗2~6周期,比较疗效和基因型之间的关系。结果:104例乳腺癌患者中,MTHFR C677T T/T基因型39例(37.5%)、C/C基因型55例(52.9%)、C/T基因型 10例(9.6%);T/T基因型化疗有效率79.5%(31/39)高于C/C基因型52.7%(29/55)和C/T基因型20.0%(2/10)（P＜0.05）。MTHFR A1298C A/A基因型41例(39.4%),A/C基因型56例(53.8%),C/C基因型7例(6.7%);各基因型化疗有效率之间无统计学关系（P＞0.05）。结论:本研究初步显示MTHFR C677T基因多态性对预测乳腺癌化疗效果具有较好的临床应用价值。     

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和ABCG2单核苷酸多态性对晚期结直肠癌—线化疗疗效的预测作用

目的:探讨亚甲基四氢叶酸还原酶(methylenetetrahydrofolate reductase,MTHFR)和乳腺癌耐药蛋白(breast cancer resistance protein,BCRP/ABCG2)基因单核苷酸多态性(single nucleotide polymorphism,SNP)对晚期结直肠癌一线化疗疗效的预测作用.方法:采用基因测序法检测154例接受FOLFOX、XELOX或FOLFIRI方案一线化疗的晚期结直肠癌患者外周血MTHFR 677C＞T、MTHFR 1298A＞C、ABCG2 34G＞A和ABCG2 421C＞A这4个位点的SNP,结合临床特征,分析其与近期疗效、无进展生存(progression-free survival,PFS)和总生存(overall survival,OS)之间的关系.结果:154例患者接受一线化疗的有效率为31.8％,中位PFS为8.1个月,中位OS为30.7个月.MTHFR和ABCG2 SNP与近期疗效和OS无显著相关性(P＞0.05).含3～4个优势基因型(MTHFR 677C/C、MTHFR 1298A/A、ABCG2 34G/A或A/A及ABCG2 421C/A或A/A)患者的中位PFS较含0～2个优势基因型患者的显著延长(分别为9.8和7.5个月,P=0.013).COX多因素分析结果显示,优势基因型数目(P=0.017)和原发灶是否根治切除(P=0.010)是影响PFS的独立因素.单因素和多因素分析结果均显示,原发灶是否根治切除是影响OS的独立因素(P=0.000,P=0.000).结论:联合分析MTHFR和ABCG2 SNP对一线化疗治疗晚期结直肠癌的PFS有一定的预测作用,原发灶是否根治切除是影响PFS和OS的独立因素.     

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.     

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,χ2=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。     

Genetic susceptibility of methylenetetrahydrofolate reductase (MTHFR) gene C677T, A1298C, and G1793A polymorphisms with risk for bladder transitional cell carcinoma in men

We performed a case-control study of 158 bladder transitional cell carcinoma (TCC) cases and 316 controls to investigate the association between methylenetetrahydrofolate reductase (MTHFR) C677T, A1298G, and G1793A polymorphisms and bladder cancer susceptibility by polymerase chain reaction restriction fragment length polymorphism (PCR-RLFP) technique. The controls were frequency-matched to the cases by age (± 5 years), ethnicity, and smoking status. We also measured serum levels of total homocysteine (tHcy), folate, and vitamin B12. It was found that the 1298AC (odds ratio, OR = 3.74; 95% confidence interval, CI = 2.34-5.47; P = 0.001) and 1298CC (OR = 3.46, 95% CI = 2.37-5.52; P = 0.001) genotypes of MTHFR A1298C were significantly associated with increased risk of bladder TCC. The MTHFR C677T and G1793A polymorphisms were not associated with bladder TCC. After stratification for grade and stage, we observed that the 677TT (OR = 4.47, 95% CI = 2.74-6.72; P = 0.001) and MTHFR 1298CC (OR = 4.78, 95% CI = 2.82-6.89; P = 0.001) genotypes of MTHFR were associated with increased risk of muscle-invasive bladder TCC. We also found that the MTHFR 677CT+1298AA genotypes were associated with an approximately 70% reduction in risk of bladder cancer (OR = 0.31; 95% CI = 0.15-0.68) compared to the combined referent genotype. There were 8 haplotypes and 16 haplotype genotypes based on these three variants. When we used the haplotypes and assumed that the 677T, 1298C, and 1793G alleles were risk alleles, the adjusted odds ratios increased as the number of risk alleles increased: 1.00 for 0-1 variant, 1.88 (1.4-2.7) for any two risk alleles and 2.07 (1.6-2.8) for any three risk alleles. Serum tHcy levels were significantly higher in carriers of the 677T, 1298C, and 1793G alleles compared to noncarriers (all P < 0.01). There was no significant correlation between serum levels of tHcy and folate and bladder cancer risk. Further studies in larger samples size and different ethnicity are required to confirm our findings.     

MTHFR基因多态性与结肠癌患者术后FOLFOX4辅助化疗疗效的关系

目的研究亚甲基四氢叶酸还原酶基因(MTHFR)C677T多态性与结肠癌术后患者接受FOLFOX4辅助化疗疗效的关系。方法对行结肠癌根治术后接受FOLFOX4方案化疗6周期的76例患者,采用焦磷酸测序法检测MTHFR C677T 基因多态。结果76例Ⅱ、Ⅲ期结肠癌患者的MTHFR-C677T位点存在3种等位基因型,其基因频率分别为：C/C 47.4%（36/76）,T/C40.8%（31/76）,T/T11.8%（9/76）。C/C 基因型36例中复发11例,T/C基因型31例中复发13例,T/T基因型9例中复发2例,T/T基因型复发比率小于C/C+ T/C基因型（22.2% vs.35.8%）,但差异无统计学意义（P=0.710）。结论MTHFR-C677T基因多态性与结肠癌FOLFOX4辅助化疗疗效无关。     

Association des polymorphismes du gène méthylène-tétrahydrofolate réductase avec la leucémie myéloïde chronique

Methylene-tetrahydrofolate reductase (MTHFR) is a key enzyme of folate metabolism. Few studies were reported about its relationship with chronic myeloid leukemia (CML). We conducted a case-control study analyzing the prevalence of the polymorphisms MTHFR C677T and MTHFR A1298C in Algerians CML patients. Using TaqMan^® allelic discrimination assay, we investigate MTHFR C677T and A1298C polymorphism distribution in 90 cases of CML and 100 healthy subjects. The frequencies of 677T alleles and genotypes 677TT and 677CT were significantly higher in cases than in control (P = 1E-6; OR = 6.77 [4.22-10.86]) and (P = 1E-6; OR = 10.38 [4.56-23.6]) respectively. Also, the frequencies of 1298C alleles and genotypes 1298CC and 1298AC were higher in cases (P = 9 E-6; OR = 2.65 [1.71-4.10]) and (P = 0.008; OR = 2.22 [1.21-4.06]) respectively. We report also the higher significance of the haplotype 677T/1298A and 677T/1298C in cases (P = 0.007; OR = 2.57 [1.26-5.24]) and (P = 5 E-6, OR = 6.91 [2.7646-17.2899]) respectively. Our results demonstrate that 677T and 1298C alleles are both associated with an increased risk of CML in Algeria.