叶酸水平、MTHFR基因C677T多态性与宫颈癌的相关性研究
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摘要
目的探讨血清叶酸及5,10-亚甲基四氢叶酸还原酶(MTHFR)基因C677T多态性与宫颈癌易感性的相关作用。方法收集82例宫颈癌患者和82例对照者,均为HPV-16阳性,应用聚合酶链反应和限制性片段长度多态性分析(PCR-RFLP)方法检测MTHFR基因C677T多态性,同时采用电化学发光法检测血清叶酸水平,对二者与宫颈癌易感性的相关性进行分析。结果病例组血清叶酸水平(8.63±5.63)μg/L低于对照组(10.84±5.99)μg/L,差异有统计学意义(t=2.43,P=0.016);两组人群的MTHFR基因C677T均为杂合型(CT)频率最高,病例组人群纯合型(TT)高于野生型(CC),与对照组不一致(χ~2=7.529,P=0.023);病例组T等位基因频率高于C等位基因,与对照组不一致(χ~2=5.903,P=0.015)。与野生型(CC)人群相比,纯合型(TT)人群患宫颈癌的危险性显著增高(OR=3.485,95%CI:1.331～9.122),而杂合型(CT)人群未发现显著影响(OR=1.752,95%CI:0.810～3.789);在叶酸充足人群中,MTHFR基因型为纯合型(TT)的人群患宫颈癌的危险为野生型(CC)人群的2.057倍(95%CI:0.455～9.304),而叶酸不充足且MTHFR基因型为纯合型(TT)的人群患宫颈癌的危险则上升为4.354倍(95%CI:1.195～15.865)。结论 MTHFR基因C677T多态性是宫颈癌发生的易感因素,纯合型(TT)可增加宫颈癌发生的危险,尤其在低叶酸水平人群中发生风险最高。
Objective To investigate the relationship between serum folate,5,10-methylene tetrahydrofolate reductase(MTHFR)gene C677 Tpolymorphism and cervical cancer.Methods The study included 82 women with cervical cancer and 82 healthy controls.Genotyping for the MTHFR C677 Tpolymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)technique.Serum folate was measured by electrochemiluminescence method.Relationships of serum folate,MTHFR gene C677 Tpolymorphism and cervical cancer were analyzed.Results The levels of serum folate in patient group[(8.63±5.63)μg/L]were significantly higher than in control group [(10.84±5.99)μg/L],the difference was statistically significant(t=2.43,P=0.016).The highest genotype frequency of MTHFR was CT type in both patient group and control group.The TT type in patient group was higher than CC type,which was significantly different in control group(χ~2=7.529,P=0.023).The allele frequency of C was higher than T in patient group,which was significantly different in control group(χ~2=5.903,P=0.015).Comparing with CC type,the risk of cervical cancer was significantly increased in patient with MTHFR gene of TT type(OR=3.485,95%CI:1.331-9.122).But there was no significantly increased risk in patients with CT type(OR=1.752,95%CI:0.810-3.789).Without folate deficiency,the odd ratios of cervical cancer in patients with MTHFR gene of TT was 2.057 times higher than that in those with wild type(CC,95%CI:0.455-9.304).With folate deficiency,the odd ratios of cervical cancer in patients with MTHFR gene of TT increased to 4.354 times than that in those with wild type(CC,95%CI:1.195-15.865).Conclusion MTHFR gene C677 T polymorphism is a susceptible factor for cervical cancer,and the TT type of this gene can increase the risk of cervical cancer.The risk of cervical cancer is the highest among people with folate deficiency and MTHFR gene of TT type.
Objective To investigate the relationship between serum folate,5,10-methylene tetrahydrofolate reductase(MTHFR)gene C677 Tpolymorphism and cervical cancer.Methods The study included 82 women with cervical cancer and 82 healthy controls.Genotyping for the MTHFR C677 Tpolymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)technique.Serum folate was measured by electrochemiluminescence method.Relationships of serum folate,MTHFR gene C677 Tpolymorphism and cervical cancer were analyzed.Results The levels of serum folate in patient group[(8.63±5.63)μg/L]were significantly higher than in control group [(10.84±5.99)μg/L],the difference was statistically significant(t=2.43,P=0.016).The highest genotype frequency of MTHFR was CT type in both patient group and control group.The TT type in patient group was higher than CC type,which was significantly different in control group(χ~2=7.529,P=0.023).The allele frequency of C was higher than T in patient group,which was significantly different in control group(χ~2=5.903,P=0.015).Comparing with CC type,the risk of cervical cancer was significantly increased in patient with MTHFR gene of TT type(OR=3.485,95%CI:1.331-9.122).But there was no significantly increased risk in patients with CT type(OR=1.752,95%CI:0.810-3.789).Without folate deficiency,the odd ratios of cervical cancer in patients with MTHFR gene of TT was 2.057 times higher than that in those with wild type(CC,95%CI:0.455-9.304).With folate deficiency,the odd ratios of cervical cancer in patients with MTHFR gene of TT increased to 4.354 times than that in those with wild type(CC,95%CI:1.195-15.865).Conclusion MTHFR gene C677 T polymorphism is a susceptible factor for cervical cancer,and the TT type of this gene can increase the risk of cervical cancer.The risk of cervical cancer is the highest among people with folate deficiency and MTHFR gene of TT type.
引文
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[11]张小莉,金平.MTHFR和XRCC3基因多态性与宫颈鳞癌发生的相关性研究[J].中华妇产科杂志,2013,48(7):545-547.
[12]BADIGA S,JOHANNING G L,MACALUSO M,et al.Alower degree of PBMC L1 methylation in women with lower folate status May explain the MTHFR C677Tpolymorphism associated higher risk of CIN in the US post folic acid fortification era[J].PLoS One,2014,9(10):e110093.
[2]CAI L M,YU R F,HAO X,et al.Folate receptor-targeted bioflavonoid genistein-loaded chitosan nanoparticles for enhanced anticancer effect in cervical cancers[J].Nanoscale Res Lett,2017,12(1):509.
[3]聂小凤,许榕仙,李健.叶酸与相关因素的交互作用对宫颈癌的影响[J].中国妇幼保健,2014,29(1):106-109.
[4]WANG Z L,WANG J T,FAN J R,et al.Risk factors for cervical intraepithelial neoplasia and cervical cancer in Chinese women:large study in Jiexiu,Shanxi Province,China[J].J Cancer,2017,8(6):924-932.
[5]何芳,杨慧娟.生活方式、膳食习惯、血清叶酸水平与宫颈癌的相关性调查[J].中国现代医生,2014,52(12):142-144.
[6]HARDI H,MELKI R,BOUGHALEB Z,et al.Significant association between ERCC2and MTHFR polymorphisms and breast cancer susceptibility in Moroccan population:genotype and haplotype analysis in a case-control study[J].BMC Cancer,2018,18(1):292.
[7]KIM K R,YOON J H,SHIM H J,et al.Role of depth of response and MTHFR genotype as predictors of fluorouracil rechallenge therapy for refractory metastatic colorectal cancer[J].Oncol Lett,2017,14(2):2491-2498.
[8]HUANG L L,DENG D H,PENG Z G,et al.Polymorphisms in the methylenetetrahydrofolate reductase gene(MTHFR)are associated with susceptibility to adult acute myeloid leukemia in a Chinese population[J].Cancer Epidemiol,2015,39(3):328-333.
[9]CHEN H,ZHU J.C677Tpolymorphism of methylenetetrahydrofolate reductase May contribute to cervical cancer risk in complete over-dominant model[J].Med Hypotheses,2013,80(5):679-683.
[10]HAJIESMAEIL M,TAFVIZI F,SARMADI S.The effect of methylenetetrahydrofolate reductase polymorphisms on susceptibility to human papilloma virus infection and cervical cancer[J].Infec Gene Evol,2016,46(1):1-6.
[11]张小莉,金平.MTHFR和XRCC3基因多态性与宫颈鳞癌发生的相关性研究[J].中华妇产科杂志,2013,48(7):545-547.
[12]BADIGA S,JOHANNING G L,MACALUSO M,et al.Alower degree of PBMC L1 methylation in women with lower folate status May explain the MTHFR C677Tpolymorphism associated higher risk of CIN in the US post folic acid fortification era[J].PLoS One,2014,9(10):e110093.