血清叶酸、维生素B12浓度及MTHFR、MS基因多态性与乳腺癌风险相关性研究

目的：分析血清中叶酸和维生素B12的含量以及甲硫氨酸合成酶（Methionine synthase,MS）及亚甲基四氢叶酸还原酶（Methylene tetrahydrofolate reduetase,MTHFR）各基因型在云南籍乳腺癌人群和正常人群中的分布差异,探索MTHFR,MS多态性与乳腺癌易感性之间的关系。方法：应用普通PCR-RFLP技术对95例云南籍乳腺癌患者和90例正常人群MS2756位点、MTHFR677位点和1298位点基因多态与乳腺癌风险关联分析筛查。同时应用全自动免疫分析仪测定血清中叶酸和维生素B12的含量。结果：乳腺癌患者血清维生素B12含量高于正常对照组,而血清叶酸低于正常对照组。云南籍乳腺癌人群和对照人群MS,MTHFR各基因型与分布频率比较无明显差异。结论：血清叶酸和维生素B12含量与乳腺癌发生风险有关,而MS,MTHFR基因多态性与乳腺癌发生风险无明显统计学意义。     

砷及MTHFR和MTR基因多态性与乳腺癌发生风险的关系

[目的]探讨尿砷与乳腺癌的关联,并分析5,10-亚甲基四氢叶酸还原酶(MTHFR)rs1801133和甲硫氨酸合成酶(MTR) rs 1805087多态性位点对其关联的影响.[方法]2009年10月至2010年7月对新诊断的240例乳腺癌患者及同时期同医院体检的246例年龄频数匹配对照进行问卷调查、尿样和血样收集.尿砷浓度采用电感耦合等离子体质谱(ICP-MS)检测;MTHFR rs1801133和MTR rs1805087基因型采用基质辅助激光解吸/电离飞行时间质谱(MALDI-TOF-MS)方法,在Sequenom平台检测.[结果]病例组和对照组尿碑含量差异无统计学意义(P=0.32).rs1801133和rs1805087在病例组和对照组中基因型分布差异无统计学意义(P＞0.05).rs1801133和rs 1805087与砷对乳腺癌发生风险不存在交互作用(P＞0.05).[结论]在本研究人群中,未发现尿砷与乳腺癌风险有关联,MTHFR rs1801133和MTR rs1805087位点对该关联的影响也无统计学意义.     

叶酸、维生素B12和亚甲基四氢叶酸还原酶基因多态性与乳腺癌风险的关系

乳腺癌是妇女最常见的癌症，也是癌症导致死亡最常见的原因。2002年，全球有115万妇女被确诊为乳腺癌，且约有41万妇女死于该病。从目前的研究现状看，乳腺癌的发生、发展除与遗传、月经初潮、月经周期、首次足月孕、哺乳、绝经年龄、环境污染、职业等因素有关外，饮食因素也已成为学者们越来越关注的另一个重要因素。     

东北地区亚甲基四氢叶酸还原酶基因C677T单核苷酸多态性与乳腺癌易感性的相关性研究

目的::研究亚甲基四氢叶酸还原酶(MTHFR)基因单核苷酸多态性与乳腺癌易感性的关系.方法:采用以人群为基础的病例对照研究方法,聚合酶链反应-限制性片段长度多态性法检测MTHFR基因型在东北地区乳腺癌患者和正常人群中的分布.结果:MTHFR基因677位点在乳腺癌组和对照组中等位基因频率及基因型分布有显著差异性(P<0.05).进一步分析表明,纯合突变G/G基因型、杂合突变C/G基因型与野生C/C基因型相比,患乳腺癌的危险度分别提高了2.23倍和2.00倍.结论:MTHFR基因C677T突变基因型与乳腺癌的易感性有关.     

亚甲基四氢叶酸还原酶基因多态性与乳腺癌相关性的研究进展

乳腺癌是一种复杂的全身性的疾病,其发病机制尚未完全清楚,但受基因及环境相互作用的影响。亚甲基四氢叶酸还原酶（MTHFR）基因位于1号染色体短臂的末端（1p36.6）,是叶酸代谢途径的关键酶,参与DNA合成、修复及甲基化过程。MTHFR基因多态性的分布在不同的种族及区域存在差异,其基因的单核苷酸突变会使该酶的生物活性及热稳定性下降,参与肿瘤的发生及发展过程,多项研究显示 MTHFR基因多态性与乳腺癌发生、发展及预后密切相关。     

MTHFR基因多态性与结直肠癌的相关性

结直肠癌是全球最常见的恶性肿瘤之一.亚甲基四氢叶酸还原酶(MTHFR)是叶酸代谢的关键酶,近年来许多研究显示其基因多态性与结直肠癌的发病率、相关抗肿瘤药物的疗效及预后相关,但结论尚不完全一致,有待更多临床研究证实.     

MTHFR基因多态性与肺癌的相关性研究

目的:探讨MTHFR基因C677T多态性与肺癌之间的关系,寻找肺癌的易感基因。方法:研究分肺癌组及正常对照组,各100例,分别利用免疫组化法进行MTH-FR基因多态性的检测。结果:PCR扩增出的MTHFR基因经HinfⅠ限制性内切酶消化后可产生3种基因型:纯合子突变(TT型)、杂合子突变(CT型)和无突变者(CC型)。肺癌组中CC型表达24例,CT型52例,TT型24例;对照组中CC型39例,CT型48例,TT型13例。两组比较,CC基因型差异有统计学意义,χ2=5·214,P=0·022;CT基因型差异无统计学意义,χ2=0·320,P=0·572;TT基因型差异有统计学意义,χ2=4·013,P=0·045。结论:MTH-FR基因C677T多态性在肺癌病例与正常人之间的分布有所不同,有助于临床早期发现肺癌的易感人群。     

叶酸缺乏与MTHFR C677 T 多态性对乳腺癌 患者淋巴细胞遗传损伤的影响

 目的　探讨叶酸缺乏与MTHFR C677 T 基因型多态性对乳腺癌患者淋巴细胞遗传损伤的影响 及其与对照的差异。方法　采用9 天淋巴细胞长期培养辅以胞质阻断微核细胞组分析(CBMN cyt) ,分 析不同浓度的叶酸对三种MTHFR C677 T 基因型乳腺癌人群和健康人群双核细胞微核率的影响与差 异。结果　MTHFR C677 T 三种基因型(CC ,CT , TT) 的乳腺癌个体与对照组淋巴细胞在叶酸浓度为 30 nmol/ L 时双核细胞微核率(MNBN) 均显著高于60 、120 、240 和2 260 nmol/ L 测试组( P < 0. 001～ 0. 05) ,60 和120 nmol/ L 两个测试组之间以及120 、240 和2 260 nmol/ L 三个测试组之间都未发现显著 性差异。乳腺癌个体和对照组淋巴细胞中,MTHFR677 TT 在任何培养条件下,MNBN 频率均显著高于 相应样本组同类培养的野生纯合型(CC) ( P < 0. 01～0. 05) ;消减样本自身遗传损伤背景后,相同基因型 的乳腺癌个体和正常个体淋巴细胞在MNBN 频率上无显著性差异。结论　在离体情况下,低于120 nmol/ L 的叶酸浓度可增加人类淋巴细胞遗传损伤,无论是健康人群还是癌症患者,MTHFR 677 TT 型 纯合个体,对叶酸缺乏都更加敏感。     

叶酸及亚甲基四氢叶酸还原酶基因多态性与乳腺癌细胞多药耐药的相关性分析

目的:探讨人乳腺癌亲本细胞株(MCF-7)及耐多柔比星乳腺癌细胞株(MCF-7/ADR)中叶酸受体(FOLR)的表达及亚甲基四氢叶酸还原酶(MTHFR)基因多态性与乳腺癌细胞多药耐药的相关性。方法:流式细胞仪检测不同浓度叶酸对MCF-7细胞及MCF-7/ADR细胞周期的影响;RT-PCR检测MCF-7细胞及MCF-7/ADR细胞中FOLR和mdr-1 mRNA的表达水平;PCR-RFLP方法检测MCF-7细胞及MCF-7/ADR细胞中MTHFR基因C677T及A1298C基因多态性。结果:当叶酸≥270nmol/L时,MCF-7和MCF-7/ADR细胞处于G0/G1期细胞数增加。在MCF-7细胞中S期细胞数在叶酸≥270 nmol/L时显著减少(P<0.001);在MCF-7/ADR细胞中S期细胞数在叶酸≥30nmol/L时开始显著减少,且随着叶酸浓度升高,S期细胞数减少更显著(P<0.001)。在两株细胞中,FOLR和mdr-1基因mRNA表达水平呈负相关,MTHFR的C677T基因多态性及A1298C转录水平无差异;但经限制性核酸内切酶反应后,MCF-7细胞的MTHFR基因有A1298C及C677T两种基因多态性;而MCF-7/ADR细胞MTHFR基因只存在C677T基因多态性。结论:叶酸对MCF-7和MCF-7/ADR细胞的DNA合成均有抑制作用,该抑制作用在MCF-7/ADR细胞中更显著,可能通过阻断细胞从G0/G1期进入S期实现。在MCF-7/ADR细胞MTHFR A1298C基因多态性消失,可能与MCF-7细胞耐药相关。     

MTHFR基因C667T位点多态性与亚洲人群乳腺癌易感性的Meta分析

目的:采用Meta分析的方法定量评价亚甲基四氢叶酸还原酶（MTHFR）基因C667T位点的多态性与亚洲人群乳腺癌易感性的关系。方法:计算机检索PubMed、Web of Science、中国生物医学文献数据库、CNKI、重庆维普和万方数据库,搜索有关MTHFR基因C667T位点的多态性与亚洲人群乳腺癌易感性的研究,检索时间截止2017年2月。采用Stata 12.0软件进行统计分析。结果:共纳入24篇病例对照研究,共计7 268例乳腺癌患者,9 223例健康对照。Meta分析结果显示:MTHFR基因C667T位点的多态性均与亚洲人群乳腺癌易感性有相关性［CC vs CT:OR=0.70,95%CI（0.60,0.83）,P=0.001;CT vs TT:OR=0.87,95%CI（0.79,0.96）,P=0.05;CC vs TT:OR=0.79,95%CI（0.72,0.88）,P=0.002;CT+TT vs CC:OR=0.81,95%CI（0.76,0.87）,P=0.001;CC+CT vs TT:OR=0.85,95%CI（0.77,0.93）,P=0.003］。结论:MTHFR基因C667T位点的多态性增加了亚洲人群乳腺癌的易感性。     

叶酸及维生素B12与肿瘤治疗的关系及研究进展

叶酸和维生素B12是人体必需的维生素,参与人体细胞的增殖。叶酸和维生素B12因其对细胞增殖和甲基化的影响,在肿瘤发生与治疗的过程中发挥着一定作用。本文概述了其延缓肿瘤发生,作为特异性靶点识别和治疗肿瘤,增强现有化疗效果,改善化疗药物所致毒副反应等方面的研究进展。     

Vitamin D receptor gene polymorphisms are associated with breast cancer risk in a UK Caucasian population.

There is increasing evidence that vitamin D can protect against breast cancer. The actions of vitamin D are mediated via the vitamin D receptor (VDR). We have investigated whether polymorphisms in the VDR gene are associated with altered breast cancer risk in a UK Caucasian population. We recruited 241 women following a negative screening mammogram and 181 women with known breast cancer. The VDR polymorphism Bsm I, an intronic 3' gene variant, was significantly associated with increased breast cancer risk: odds ratio bb vs BB genotype = 2.32 (95% CI, 1.23-4.39). The Bsm I polymorphism was in linkage disequilibrium with a candidate translational control site, the variable length poly (A) sequence in the 3' untranslated region. Thus, the 'L' poly (A) variant was also associated with a similar breast cancer risk. A 5' VDR gene variant, Fok I, was not associated with breast cancer risk. Further investigations into the mechanisms of interactions of the VDR with other environmental and/or genetic influences to alter breast cancer risk may lead to a new understanding of the role of vitamin D in the control of cellular and developmental pathways.     

Association of Dietary Intake of Folate,Vitamin B6 and B12 and MTHFR Genotype with Breast Cancer Risk

Aim: We aimed to investigate the associations of dietary intake of folate, vitamin B6 and B12 and MTHFRgenotype with breast cancer in a Chinese population. Methods: A matched case-control study was conducted, and435 patients with newly diagnosed and histologically confirmed breast cancer and 435 controls were collected. Thefolate intake, vitamin B6 and vitamin B12 were calculated, and MTHFR C665T, C677T and A1298C were analyzedby PCR-RFLP. Results: We found vitamin B12 was likely to reduce the risk of breast cancer, and MTHFR 665TTwas associated with increased risk of breast cancer. Folate intake, vitamin B12 intake and variants of MTHFRC677T and MTHFR A1298C demonstrated no association with risk of breast cancer. However, we found patientswith low intake of vitamin B6 and MTHFR 665TT genotype had a higher risk of breast cancer (OR=1.87, 95%CI=1.29-2.77), the association being less pronounced among subjects with a moderate intake of vitamin B6 andMTHFR 665TT genotype (OR=1.58, 95% CI=1.03-2.49, P=0.03). Conclusion: Our study indicated that theMTHFR C665T polymorphism and vitamin B6 are associated with risk of breast cancer, which indicated rolesfor nutrients in developing breast cancer.     

Biomarkers of folate and vitamin B12 and breast cancer risk: report from the EPIC cohort

Epidemiological studies have reported inconsistent findings for the association between B vitamins and breast cancer (BC) risk. We investigated the relationship between biomarkers of folate and vitamin B12 and the risk of BC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Plasma concentrations of folate and vitamin B12 were determined in 2,491 BC cases individually matched to 2,521 controls among women who provided baseline blood samples. Multivariable logistic regression models were used to estimate odds ratios by quartiles of either plasma B vitamin. Subgroup analyses by menopausal status, hormone receptor status of breast tumors (estrogen receptor [ER], progesterone receptor [PR] and human epidermal growth factor receptor 2 [HER2]), alcohol intake and MTHFR polymorphisms (677C > T and 1298A > C) were also performed. Plasma levels of folate and vitamin B12 were not significantly associated with the overall risk of BC or by hormone receptor status. A marginally positive association was found between vitamin B12 status and BC risk in women consuming above the median level of alcohol (OR_Q4‐Q1 = 1.26; 95% CI 1.00–1.58; P_trend = 0.05). Vitamin B12 status was also positively associated with BC risk in women with plasma folate levels below the median value (OR_Q4‐Q1 = 1.29; 95% CI 1.02–1.62; P_trend = 0.03). Overall, folate and vitamin B12 status was not clearly associated with BC risk in this prospective cohort study. However, potential interactions between vitamin B12 and alcohol or folate on the risk of BC deserve further investigation.     

同型半胱氨酸、维生素D、C、E、B12及叶酸与胃癌关系的研究进展北大核心

胃癌作为临床最常见的肿瘤之一,常因确诊疾病较晚而影响治疗效果,胃镜活检后的病理虽然作为确诊的金标准,但是由于此方式过程痛苦,操作复杂,费用较高,且具有侵入性,可能会导致患者拒绝操作而难普及于临床,因此积极找寻胃癌有效的监测指标十分必要。近年来,很多学者研究维生素与胃癌的相关关系,并试图通过摄取某些维生素降低胃癌发生率,延缓病情及改善预后,也有通过检测血清中维生素的水平给早期胃癌的诊断提供帮助。本文就同型半胱氨酸、维生素D、维生素C、维生素E、维生素B12及叶酸在胃癌中的作用机制,及其在血清中水平与胃癌关系的相关研究进展进行简要综述,为临床胃癌诊疗提供新思路。     

Plasma folate, vitamin B12, and homocysteine and prostate cancer risk: a prospective study

The role of folate metabolism in cancer development is a topic of much current interest, with maintenance of adequate folate status tending to show a protective effect. Aberrant methylation, primarily hypermethylation of certain genes including tumor suppressors, has been implicated in prostate cancer development. Folate, vitamin B12 and homocysteine are essential for methyl group metabolism and thus also for DNA methylation. We related plasma levels of these factors to prostate cancer risk in a prospective study of 254 case subjects and 514 matched control subjects. Increasing plasma levels of folate and vitamin B12 were statistically significantly associated with increased prostate cancer risk, with an odds ratio of 1.60 (95% CI = 1.03-2.49; p(trend) = 0.02) for folate and 2.63 (95% CI = 1.61-4.29; p(trend) < 0.001) for vitamin B12 for highest vs. lowest quartile. Increasing plasma homocysteine levels were associated with a reduced risk of borderline significance (OR = 0.67; 95% CI = 0.43-1.04; p(trend) = 0.08). After adjustment for the other 2 plasma variables, body mass index and smoking, a statistically significant increased risk remained only for vitamin B12 (OR = 2.96; 95% CI = 1.58-5.55; p(trend) = 0.001). Adjusted OR for folate and homocysteine were 1.30 (95% CI = 0.74-2.24; p(trend) = 0.17) and 0.91 (95% CI = 0.51-1.58; p(trend) = 0.60), respectively. Our results suggest that factors contributing to folate status are not protective against prostate cancer. On the contrary, vitamin B12, associated with an up to 3-fold increase in risk, and possibly also folate, may even stimulate prostate cancer development. These findings are novel and should be explored further in future studies.     

维生素B12混合液治疗乳腺癌术后放疗急性放射性皮肤损伤初步观察

目的:探讨乳腺癌术后放疗患者急性放射性皮肤损伤的防治方法。方法:对2004年10月～2005年12月我院86例乳腺癌术后放疗患者出现I级放射性皮肤损伤出现滤泡样暗色红斑/出汗减少时(一般DT30GY/3W)即进行配对分组治疗,实验组用维生素B12混合液(VitB12500μg×20支 0.9%生理盐水250ml 庆大霉素48万U 地塞米松20mg)纱布浸湿外敷,15～20分钟/次,2～3次/日,7天为1疗程,连用2个疗程;对照组单用康复新液湿敷,用法疗程同上。结果:放射治疗结束时皮肤损伤实验组:I级62.79%(27/43);II级27.91%(12/43);III级9.30%(4/43);IV级0(0/43)。对照组皮肤损伤:I级18.60%(8/43);II级55.81%(24/43);III级20.93%(9/43);IV级4.65%(2/43)。两组差异非常显著性,(P<0.01)。结论:乳腺癌术后放疗患者急性放射性皮肤损伤重在早期预防和治疗,维生素B12混合液湿敷是治疗急性放射性皮肤损伤的一种既经济又有效的方法。     

Plasma vitamin B12 concentrations and the risk of colorectal cancer: a nested case-referent study

In this nested case-referent study, we related plasma concentrations of vitamin B12 to the risk of colorectal cancer, taking into consideration prediagnostic plasma folate and total homocysteine concentrations. Subjects were 226 cases and double matched referents from the population-based Northern Sweden Health and Disease Study. Follow-up times from recruitment to diagnosis ranged from 0.1 to 12.7 years, with a median of 4.2 years. Plasma vitamin B12 concentrations were inversely associated with the risk of rectal cancer: univariate odds ratio for the highest versus lowest quintile 0.34 (95% confidence interval (95% CI) 0.13-0.83), p(trend) = 0.004. Risk estimates were attenuated slightly but remained statistically significant after adjustment for body mass index, current smoking, recreational and occupational physical activity, alcohol intake and prediagnostic plasma folate and total homocysteine concentrations: OR 0.30 (95% CI 0.08-0.99), p(trend) = 0.025. The corresponding univariate and fully adjusted odds ratios for colon cancer were 1.25 (CI 0.66-2.36), p(trend) = 0.185 and 1.42 (CI 0.67-3.05), p(trend) = 0.113, respectively. The observed over-risk was attributable to left-sided colon cancer. Interaction analyses including vitamin B12, folate and homocysteine were in line with the results for vitamin B12 alone. In conclusion, these results suggest that increasing levels of plasma vitamin B12, alone or together with other factors involved in one-carbon metabolism, may reduce the risk of rectal cancer, whereas for colon cancer, the association appears to be less clear.     

Serum total folate, 5-methyltetrahydrofolate and vitamin B12 concentrations on incident risk of lung cancer

Tobacco smoking is a major known risk factor for lung cancer. While micronutrients, especially those involved in maintaining DNA integrity and regulating gene expression, may be protective, research on this association is limited. This report aimed to investigate associations of total folate, 5-methyltetrahydrofolate (5-mTHF) and vitamin B12 with incident risk of lung cancer, and whether the associations vary by smoking status. A nested case-control study with 490 incident lung cancer cases and 490 controls matched by age (±1 year), sex, residence, and center, drawn from a community-based prospective study in China, was conducted from 2016 to 2019. 5-mTHF accounted for the majority of total folate. Only 4.4% had detectable unmetabolized folic acid. Lung cancer cases had lower levels of 5-mTHF compared to controls. There was an inverse, nonlinear association between 5-mTHF and lung cancer, which persisted after adjustment for covariables (P for trend = .001). Compared to the lowest 5-mTHF quartile, those in higher quartiles had lower risks of lung cancer: second quartile OR = 0.65; 95% CI: 0.45-0.93; third quartile OR = 0.50; 95% CI: 0.34-0.74; fourth quartile OR = 0.56; 95% CI: 0.38-0.83. This inverse association was more pronounced among ever smokers; consistently, the highest risk of lung cancer (OR = 3.21, 95% CI: 1.97-5.24) was observed among ever smokers with low 5-mTHF levels compared to participants who never smoked and had higher 5-mTHF levels. Vitamin B12 was not associated with lung cancer risk. In this sample of Chinese adults without confounding by unmetabolized folic acid, higher levels of 5-mTHF were associated with lower risk of incident lung cancer.