Associations between methylenetetrahydrofolate reductase polymorphisms and hepatocellular carcinoma risk in Chinese population

Genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene are considered to have some influence on both folate metabolism and cancer risk. Previous studies on the associations of MTHFR genetic polymorphisms with hepatocellular carcinoma (HCC) risk in Chinese population reported inconsistent results. We performed this meta-analysis to comprehensively assess the associations. Finally, 12 individual case–control studies were included into the meta-analysis. There were seven studies (6,384 subjects) on the MTHFR C677T polymorphism and five studies (4,502 subjects) on the MTHFR A1298C polymorphism. Overall, MTHFR C677T polymorphism was significantly associated with susceptibility to HCC in Chinese population (T versus C, odds ratio (OR)?=?1.09, 95 % confidence interval (95 % CI) 1.01–1.17; TT versus CC, OR?=?1.17, 95 % CI 1.00–1.38; TT/CT versus CC, OR?=?1.12, 95 % CI 1.00–1.26). MTHFR A1298C polymorphism was conversely associated with HCC risk in Chinese population (CC versus AA, OR?=?0.65, 95 % CI 0.46–0.91; CC versus AA/AC, OR?=?0.64, 95 % CI 0.46–0.90). The sensitivity analysis confirmed the reliability and stability of the meta-analysis. Thus, the findings from our meta-analysis support the associations of MTHFR C677T and A1298C polymorphisms with HCC risk in Chinese population.     

Association of candidate genetic variations with gastric cardia adenocarcinoma in Chinese population: a multiple interaction analysis

Single genetic variation may only have a modest effect on risk of gastric cardia adenocarcinoma (GCA) because this malignancy is believed to result from complex interactions among multiple genetic and environmental factors. However, it has been a challenge to characterize multiple interactions using parametric analytic approaches. This study utilized a multi-analytic strategy combining logistic regression (LR), multifactor dimensionality reduction (MDR) and classification and regression tree (CART) approaches to explore high-order interactions among smoking and 12 polymorphisms involved in different processes of carcinogenesis in 344 GCA patients and 324 controls. LR, MDR and CART analyses consistently suggested MMP-2 C-1306T polymorphism as the strongest individual factor for GCA risk. Intriguingly, a high-order interaction was consistently identified by MDR, LR and CART analyses. In MDR analysis, the three-factor model including MMP-2 C-1306T, FASL T-844C and FAS G-1377A yielded the highest testing accuracy of 0.632. When analysing combined effect of these three polymorphisms by LR, a significant gene dose effect was observed with the odds ratios (ORs) being increased with increasing numbers of risk genotypes (P(trend) = 4.736 × 10?12). In CART analysis, individuals carrying the combined genotypes of MMP-2 -1306CC, FASL-844TT or TC and FAS -1377AA had the highest risk for GCA (OR = 4.58; 95% confidence interval, 2.07-10.14) compared with the lowest risk carriers of the MMP-2 -1306CT or TT genotype. These results suggest that MMP-2 C-1306T polymorphism is an important risk factor for GCA and the multifactor interactions among polymorphisms in MMP-2, FASL and FAS play more important role in the development of GCA.     

GST genetic polymorphisms and lung adenocarcinoma susceptibility in a Chinese population

Lung adenocarcinoma (AC) has been increasing over the last several decades in many countries, including China. Some of the glutathione S-transferases (GSTs) demonstrate polymorphisms which may play a role in lung AC susceptibility. Our previous study of a Chinese population found the GSTM1 null genotype to be associated with an increased risk of lung AC, and the combination of GSTM1 null genotype and CYP2E1 wild type conferred a significantly elevated risk. Here, we extended the study to investigate the potential role of GSTT1 and GSTP1 polymorphisms in likelihood of development of lung AC, either separately or in combination. This case-control study encompassed 112 cases with lung ACs and 119 age- and gender-matched cancer-free controls from Beijing. The frequencies for the GSTM1 null genotype were 61.6 and 50.4% among cases and controls, and for the GSTT1 null genotype 47.3 and 45.4%, respectively. The distribution of the GSTP1 Ile/Ile, Ile/Val and Val/Val genotypes was 59.8, 39.3 and 0.9% in cases, and 70.6, 28.6 and 0.8% in controls, respectively. No relationship between lung AC and the GSTT1 genotype was observed in the present study, either separately or in combination with the GSTM1 or GSTP1 genotypes. Although separate GSTM1 and GSTP1 polymorphisms were not statistically related to lung AC, the combination of GSTM1 null and GSTP1 Val was significantly associated with an elevated lung AC risk (OR=2.4, 95% CI 1.1-5.1).     

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。     

Methylenetetrahydrofolate reductase polymorphisms,serum methylenetetrahydrofolate reductase levels,and risk of childhood acute lymphoblastic leukemia in a Chinese population

(Cancer Sci 2010; 101: 782–786) Methylenetetrahydrofolate reductase (MTHFR), involved in DNA methylation and nucleotide synthesis, is thought to be associated with a decreased risk of adult and childhood acute lymphoblastic leukemia (ALL). Accumulating evidence has indicated that two common genetic variants, C677T and A1298C, are associated with cancer risk. We hypothesized that these two variants were associated with childhood ALL susceptibility and influence serum MTHFR levels. We genotyped these two polymorphisms and detected MTHFR levels in a case–control study of 361 cases and 508 controls. Compared with the 677CC and 677CC/CT genotypes, the 677TT genotype was associated with a statistically significantly decreased risk of childhood ALL (odds ratio = 0.53, 95% confidence interval = 0.32–0.88, and odds ratio = 0.55, 95% confidence interval = 0.35–0.88, respectively). In addition, a pronounced reduced risk of ALL was observed among low‐risk ALL and B‐phenotype ALL. Moreover, the mean serum MTHFR level was 8.01 ng/mL (±4.38) in cases and 9.27 ng/mL (±4.80) in controls (P < 0.001). MTHFR levels in subjects with 677TT genotype was significantly higher than those with 677CC genotype (P = 0.010) or 677CT genotype (P = 0.043) in controls. In conclusion, our results provide evidence that the MTHFR polymorphisms might contribute to reduced childhood ALL risk in this population.     

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。     

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.     

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.     

The rising trend in oesophageal adenocarcinoma and gastric cardia.

The incidence of cancer of the oesophagus and stomach in the West Midlands region of England have been analysed for the 25 years 1962-86. Overall, cancer of the oesophagus is increasing (from 3.45 per 100,000 in 1962-66 to 4.37 in 1982-86) and stomach cancer is decreasing (19.22 and 16.54 respectively). However, when analysed by histological type and subsite the picture is very different. In oesophagus, squamous cell carcinoma shows only a slight increase whereas for adenocarcinoma the increase is highly significant (from 0.14 to 0.76). In stomach, cardia shows a very similar pattern to adenocarcinoma of oesophagus (increasing from 0.75 to 2.96) but pyloric antrum is decreasing (from 2.63 to 2.32). The rapid changes in investigative procedures over the period have resulted in increasing numbers with histological confirmation and subsite specification but despite these confounding factors, comparative analyses still indicate a real increase in adenocarcinoma of oesophagus and cardia. Although the incidence of both are greater in men than in women, the proportional rates of increase, particularly for cardia, are very similar in both sexes, indicating a common aetiological factor or factors. Analysis by social-economic group reveals that the increases observed are not uniform throughout the population but are relatively higher in professional classes (1 and 2).     

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。     

Esophageal skip metastasis from an adenocarcinoma of the gastric cardia

Although diffuse‐type gastric carcinomas sometimes spread within the esophageal mucosa, a distant skip metastasis from a gastric carcinoma to the esophagus wall has rarely been reported. We herein report the case of a patient found to have a carcinoma of the gastric cardia with a skip metastasis to the esophagus, approximately 10 cm distant from the esophagogastric junction. A 53‐year‐old man was admitted to our department suffering from a sudden hematemesis. An upper gastrointestinal endoscopic study revealed an infiltrative ulcerating tumor of the gastric cardia and a small, reddish, elevated submucosal tumor on the middle third of the esophagus, apart from the tumor on the cardia. A histological study of the biopsy specimens from both tumors showed poorly differentiated adenocarcinomas. The patient underwent total thoracic esophagectomy and proximal gastrectomy combined with a splenectomy through a cervicoabdominal approach. The resected specimen contained a tumor of the cardia, 7.4 × 5.1 cm in area, that had infiltrated the submucosal layers of the lower esophagus up to 2.0 cm from the esophagogastric junction. The skip metastases were located 0.5, 4 and 7.2 cm from the oral side of the main tumor.     

Allelotype analysis of adenocarcinoma of the gastric cardia.

To identify chromosomal loci involved in the development of proximal gastric adenocarcinoma, this study delineated the pattern of allelic imbalance in a series of 38 adenocarcinomas arising in the gastric cardia. A total of 137 microsatellite markers covering all autosomal arms, excluding acrocentric arms, were analysed. A mean of 35 out of a total of 39 chromosomal arms studied were informative for each patient. The tumour group demonstrated a high level of allelic imbalance, with an observed median fractional allelic imbalance of 0.47 for the 29 intestinal-type adenocarcinomas and 0.54 for the nine diffuse-type adenocarcinomas. Allelic imbalance was detected in >50% of informative cases in both histological subtypes on a number of chromosomal arms. In the intestinal subtype, these included, 3p (61%), 4q (71%), 5q (59%), 8p (60%), 9p (65%), 9q (83%), 12q (52%), 13q (52%), 17p (78%) and 18q (70%). A higher incidence of allelic imbalance was detected on chromosome 16q in tumours of the diffuse type relative to those of the intestinal type. A more detailed mapping on chromosomes 4q and 6q identified a number of cases with subchromosomal breakpoints. In conclusion, this analysis has indicated regions of the genome potentially involved in the development of proximal gastric carcinomas.     

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。     

Genetic polymorphisms of methylenetetrahydrofolate reductase and colorectal cancer and adenoma

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme regulating folate metabolism, which affects DNA methylation and synthesis. Two functional, common polymorphisms (C677T and A1298C) are known in the MTHFR gene. MTHFR activity is lowered in individuals with the 677TT genotype and is somewhat reduced in those with the 1298CC genotype. We reviewed the consistency of reported associations of these polymorphisms with colorectal cancer and adenoma with consideration of the effects of nutritional status. A total of 16 studies have addressed the association between MTHFR C677T polymorphism and colorectal cancer in 10 countries. Decreased risk of colorectal cancer associated with the 677TT genotype has fairly consistently been observed, with few exceptions. This decrease was observable in people with either high or low folate status. Alteration in the thymidylate pool associated with MTHFR activity is postulated as an underlying mechanism. Studies on the A1298C polymorphism are limited, and their results are variable. Almost all of seven studies of colorectal adenoma have found no association between C677T polymorphism and adenoma, but the 677TT genotype seems to be related to increased risk when folate status is poor. Reduced availability of methyl groups for DNA methylation might be more relevant to adenoma formation. Although the underlying mechanisms still remain to be clarified, epidemiological findings regarding MTHFR C677T polymorphism provide strong evidence that adequate folate status confers protection from colorectal cancer.     

Systematic review on the relationship between genetic polymorphisms of methylenetetrahydrofolate reductase and esophageal squamous cell carcinoma

Background: Both genetic and environmental factors play roles in pathogenesis of esophageal squamouscell carcinoma (ESCC) and susceptibility may be modified by functional polymorphisms in folate metabolicgenes, such as methylenetetrahydrofolate reductase (MTHFR). We here aimed to evaluate associations ofMTHFR C677T and A1298C polymorphisms with ESCC. Methods: We searched MEDLINE, EMBASE andthe Chinese Biomedical Database and 2 evaluators independently reviewed all the articles identified accordingto predetermined criteria. Results: A total of 15 case-control studies published between 2001 and 2010 wereincluded. When all the studies were pooled, the crude odds ratio (95% CI) of ESCC for individuals carryingMTHFR 677 CT and TT genotypes, as compared to CC, were 1.39 (1.11-1.75) and 1.79 (1.31-2.43), respectively.Individuals with MTHFR 1298CC showed non-significantly increased risk of ESCC, with an OR (95%CI) of3.31(0.90-12.17). In smokers, a significantly increased risk of ESCC was observed for those with the MTHFR677T allele (OR (95% CI)=2.2 (1.31-2.41)). Chinese carrying MTHFR 677T and MTHFR 1298C alleles had agreater increase in ESCC risk than other ethnicities. Conclusions: The present meta-analysis provided evidencethat MTHFR 677CT/TT plays a carcinogenic role in ESCC, and its effect is modified by tobacco and ethnicity.The small number of subjects with the MTHFR 1299C allele genotype in published studies limits conclusionsregarding this polymorphism.     

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。     

Methylenetetrahydrofolate reductase 677C/T gene polymorphism, gastric cancer susceptibility and genomic DNA hypomethylation in an at-risk Italian population

We performed a case-control study to examine the relationship between MTHFR C677T gene polymorphism (MTHFR677C/T) and gastric cancer susceptibility in at-risk populations in central Italy. To explore genomic DNA hypomethylation as a potential etiologic mechanism, this phenomenon was evaluated in carriers of the MTHFR677T/T genotype and carriers of the wild-type MTHFR677C/C genotype. Lymphocyte genomic DNA from 162 gastric cancer patients and 164 controls was used for MTHFR677C/T genotyping. Unconditional regression analysis with ORs and 95% CIs was used to investigate the association of the polymorphism with disease. Genomic DNA methylation status by an established enzymatic assay that measures the DNA accepting capacity of methyl groups (inversely related to endogenous methylation) was assessed in a random sample of 40 carriers of the wild-type MTHFR677C/C genotype and 40 carriers of the MTHFR677T/T genotype. The global allelic distribution was in Hardy-Weinberg equilibrium. The MTHFR677T allele was significantly associated with gastric cancer risk with an OR of 2.49 (95% CI 1.48-4.20) in heterozygous MTHFR677C/T carriers and an OR of 2.85 (95% CI 1.52-5.35) in homozygous MTHFR677T/T carriers. This risk association was retained in subgroup analyses by tumor histotype and location. Genomic DNA hypomethylation status in MTHFR677T/T carriers was significantly higher than in subjects with wild-type MTHF677C/C genotype (p = 0.012). In the studied population, MTHFR677T played the role of a moderate-penetrance gastric cancer susceptibility allele. Possession of the MTHFR677T/T genotype was significantly associated with genomic DNA hypomethylation. These findings deserve further investigation in the context of novel strategies for gastric cancer prevention.     

贲门癌蛋白质组与病理分化程度的研究

目的：筛选贲门癌相关肿瘤标志。方法：IMAC3芯片及SELDI-TOF技术检测河南省林州市食管／贲门癌高发区47例贲门癌患者（贲门癌组）和50名健康人（对照组）血清标本，并对32例高、中分化腺癌（高分化组）和15例低分化腺癌（低分化组）及健康人（对照组）作了对比分析。结果：以M5908．48、M7943．64和M8938．70蛋白质组成的决策树模型对贲门癌组和对照组进行分析，测试的准确率、敏感度和特异度分别为77．3％、85．1％和70．0％。差异有统计学意义的蛋白中，相对分子质量为4211．29、5334．13、5966．63、5903．14、11735．71、5922．70、7932．54、7758．66、9287．40和6109．99，上调组蛋白质中，9／10相对含量在3组中比较为：对照组〈高分化组〈低分化组；相对分子质量为8992．89、8158．48、8924．27、4495．96、9434．40、5099．02、6661．72、6222．12和6960．60下调组蛋白质中，6／9为：对照组〉低分化组〉高分化组。结论：5908．48、7943．64和8938．70蛋白质组成的决策树模型可以对贲门癌进行诊断，具有较高的敏感度和特异性；上调组蛋白质在血清中的相对含量与分化程度呈负相关，下调组蛋白质与肿瘤的分化程度也明显相关。