MTHFR基因A1298C多态性与肠癌遗传易感相关性研究

目的：探讨亚甲基四氢还原酶基因（MTHFR）第7外显子区单核苷酸多态（single nucleotide polymo-rphism,SNP）位点A1298C（rs1801131）与中国南方人群肠癌发生的相关性。方法：应用基质辅助激光解吸电离飞行时间（MALDI-TOF）质谱检测224例肠癌和224例对照MTHFR基因多态位点rs1801131的基因型。结果：MTHFR rs1801131多态位点AA、AC、CC三种基因型在肠癌的频率为63.4%、32.6%和4.0%,与对照组（68.8%,29.9%和3%）相比差异不显著（P=0.12）;但男性人群中病例组和正常组的基因型差异接近显著（P=0.05）,携带CC基因型男性个体的肠癌发病风险显著增加（OR=8.38,95%CI：1.01-69.64）;相对于直肠癌,结肠癌与正常对照的基因型频率差别更大,P值分别为0.84和0.08;且男性结肠癌患者基因型分布和对照差异显著（P=0.01）。结论：MTHFR基因第7外显子区rs1801131位点的单核苷酸多态性可能与中国南方人群结肠癌的遗传易感性相关,而与直肠癌无关,特别是在男性人群中rs1801131 CC和CA基因型可能增加个体患结肠癌的风险。     

MTHFR基因A1298C多态性与肠癌遗传易感相关性研究

目的:探讨亚甲基四氢还原酶基因(MTHFR)第7外显子区单核苷酸多态(single nucleotide polymorphism,SNP)位点A1298C(rs1801131)与中国南方人群肠癌发生的相关性.方法:应用基质辅助激光解吸电离飞行时间(MALDI-TOF)质谱检测224例肠癌和224例对照MTHFR基因多态位点rs1801131的基因型.结果:MTHFR rs1801131多态位点AA、AC、CC三种基因型在肠癌的频率为63.4%、32.6%和4.0%,与对照组(68.8%,29.9%和3%)相比差异不显著(P=0.12);但男性人群中病例组和正常组的基因型差异接近显著(P=0.05),携带CC基因型男性个体的肠癌发病风险显著增加(OR=8.38,95%CI:1.01-69.64);相对于直肠癌,结肠癌与正常对照的基因型频率差别更大,P值分别为0.84和0.08;且男性结肠癌患者基因型分布和对照差异显著(P=0.01).结论:MTHFR基因第7外显子区rs1801131位点的单核苷酸多态性可能与中国南方人群结肠癌的遗传易感性相关,而与直肠癌无关,特别是在男性人群中rs1801131 CC和CA基因型可能增加个体患结肠癌的风险.     

单核苷酸多态性与肺癌化疗疗效及预后相关研究进展

单核苷酸多态性（single nucleotide polymorphism，SNP），指基因组DNA序列中频率大于1％的单个核苷酸的变异，这种变异有时导致其编码的蛋白结构和功能发生改变，从而影响其生物学功能。在肿瘤治疗领域表现为不同SNP基因型患者对治疗发生不同的反应．目前SNP与非小细胞肺癌疗效相关研究的主要基因包括DNA切除修复基因、基质金属蛋白酶基因、凋亡相关基因、药物代谢相关基因、细胞周期渊控綦因等。我们就SNP与肺癌化疗的疗效以及预后的相关性进行了综述。     

A single nucleotide polymorphism in the transmembrane domain coding region of HER-2 is associated with development and malignant phenotype of gastric cancer

Alterations of the HER-2 (erbB-2/neu) proto-oncogene have been associated with carcinogenesis and poor prognosis of certain cancers. A single nucleotide polymorphism (Ile/Val, A/G) in the transmembrane domain was reported to be associated with a risk of breast cancer. In our study, we examined the association between the HER-2 polymorphism and gastric carcinoma. The Ile/Ile, Ile/Val and Val/Val genotypes were found in 146 (68.9%), 56 (26.4%) and 10 (4.7%) of 212 gastric cancer patients and in 234 (81.5%), 48 (16.7%) and 5 (1.8%) of 287 control subjects, respectively. The Ile/Val or Val/Val genotype was significantly more frequent in patients than in controls (p = 0.005 and 0.033, respectively). The OR of Val/Val genotype then revealed a significantly enhanced risk of 3.25 (95% CI 1.09-9.70) compared to Ile/Ile genotype; heterozygous Ile/Val genotype showed an intermediate risk of 1.97 (1.27-3.06). In patients, carcinomas of advanced stage were significantly more frequent in patients with Ile/Val or Val/Val genotype than those with Ile/Ile genotype (p < 0.001). The logistic regression analysis for tumor invasion, lymph node metastasis and distant metastasis revealed that lymph node metastasis was most closely associated with the HER-2 genotype. These results suggest that this nucleotide polymorphism in the transmembrane domain-coding region of HER-2 could be associated with development of gastric carcinoma and may serve as a predictor of risk for a malignant phenotype of gastric cancer. The association of HER-2 genotype with clinicopathologic characteristics of gastric cancer was also suggested, which has to be confirmed with a larger sample size.     

Expression level of hTERT is regulated by somatic mutation and common single nucleotide polymorphism at promoter region in glioblastoma

We investigated the role of somatic mutations and a common single nucleotide polymorphism (SNP) in the hTERT promoter region on hTERT expression and clinical outcomes. The hTERT promoter region was sequenced from 48 glioblastomas. hTERT expression was analyzed by quantitative real time-PCR. The association between hTERT promoter genetic changes and other genomic events and clinical variables common in gliomas were examined. C228T and C250T somatic mutations were found in 60.4% of glioblastomas, and a common SNP (T349C) was found in 66.6%. Somatic mutations and the SNP likely have opposing effects on hTERT expression. hTERT expression was significantly higher in the C228T or C250T mutated tumors. Tumors with the T349C genotype showed lower hTERT expression when C228T or C250T mutations were present. However, no significant survival differences were observed among the groups with or without hTERT promoter mutations and SNP. There was a significant association between genetic changes in the hTERT promoter and patient age as well as MGMT promoter methylation and EGFR amplification. hTERT expression is modulated by somatic mutations in the hTERT promoter as well as a common polymorphism. However, hTERT related genomic changes have limited value as an independent prognostic factor for clinical outcomes in glioblastomas.     

胃癌相关易感基因单核苷酸多态性研究进展

胃癌具有一定程度的遗传易感性,可能与人群中存在基因多态性有关.近来,胃癌易感性与基因单核苷酸多态性的相关性研究逐渐增加并取得长足进展,目前研究的基因包括细胞增殖基因、酶基因、癌基因与抑癌基因等.     

MCM7基因启动子区-153A〉T多态位点对宫颈癌遗传易感性及基因转录活性的影响

目的：探讨MCM7基因启动子区-153A〉T多态位点（rs1534310）与宫颈癌遗传易感性的关系及对基因转录活性的影响。方法：利用聚合酶链式反应一限制性片段长度多态性（PCR—RFLP）分析技术，对87例宫颈癌患者和116名健康对照的MCM7—153A〉T多态位点进行分型，采用非条件逻辑回归分析统计该多态位点与宫颈癌易感性的相关性。构建含-153A〉T多态位点所在启动子区的双荧光报告载体，分析MCM7基因启动子区-153A〉T多态位点对基因转录活性的影响。结果：TT、AT、AA基因型在病例组中的频率分别为23．O％、46．O％和31．O％，在对照组中分别是27．6％、44．0％和28．4％，两组间基因型频率分布差异无统计学意义（P=0．753）。非条件逻辑回归分析发现，以TT基因型作为参照，AT和AA基因型均没有显著增加个体患宫颈癌的风险（OR=1．26，95％CI=0．63—2．52，P=0．522以及OR=0．54，95％CI=0．62—2．79，P=0．485）。双荧光素酶报告基因分析结果显示含有-153A或T等位基因的启动子转录活性没有显著性差异（P=0．825）。结论：MCM7—153A〉T多态位点不影响基冈转录的活性，并且与广东汉族妇女宫颈癌易感性无相关性。     

Germline variation in NCF4, an innate immunity gene,is associated with an increased risk of colorectal cancer

Chronic inflammation has been implicated in the etiology of colorectal adenoma and cancer; however, few key inflammatory genes mediating this relationship have been identified. In this study, we investigated the association of germline variation in innate immunity genes in relation to the risk of colorectal neoplasia. Our study was based on the analysis of samples collected from the prostate, lung, colorectal and ovarian (PLCO) Cancer Screening Trial. We investigated the association between 196 tag single nucleotide polymorphisms (SNPs) in 20 key innate immunity genes with risk of advanced colorectal adenoma and cancer in 719 adenoma cases, 481 cancer cases and 719 controls. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CIs). After Bonferroni correction, the AG/GG genotype of rs5995355, which is upstream of NCF4, was associated with an increased risk of colorectal cancer (OR = 2.43, 95% CI = 1.73–3.39; p < 0.0001). NCF4 is part of the NAPDH complex, a key factor in biochemical pathways and the innate immune response. While not definitive, our analyses suggest that the variant allele does not affect expression of NCF4, but rather modulates activity of the NADPH complex. Additional studies on the functional consequences of rs5995355 in NCF4 may help to clarify the mechanistic link between inflammation and colorectal cancer.     

SCN10A rs12632942 单核苷酸多态性与结直肠癌化疗奥沙利铂外周神经毒性的相关性

[摘要] 目的：探讨SCN10A基因外显子区rs12632942 位点多态性与结直肠癌（CRC）患者化疗奥沙利铂外周神经毒性（OXLIPN）的相关性。方法：选取2011 年1 月至2013 年6 月广州医科大学附属第二医院、南昌大学第二附属医院、广州市白云区中医医院319 例接受含奥沙利铂（OXL）化疗方案的CRC患者（均为中国中南地区汉族）血液标本,常规提取DNA、PCR扩增及分析SCN10A外显子多态位点rs12632942 基因型,评估OXLIPN程度。通过单因素卡方检验、Logistic 多因素回归分析评估外显子多态rs12632942 基因型与OXLIPN 的相关性。结果：319 例CRC 患者rs12632942 基因型：AA134 例、AG156 例、GG29 例,rs12632942 基因型频率符合哈温平衡（P>0.05）。rs12632942 的AG+GG基因型与Ⅱ~Ⅳ度OXLIPN相关（P<0.01）,是发生Ⅱ~Ⅳ度OXLIPN的独立危险因素（OR=2.044,95%CI=1.231~3.392,P<0.01）。结论：SCN10A基因外显子区rs12632942AG+GG基因型的CRC患者易感Ⅱ~Ⅳ度OXLIPN。     

Association of a single nucleotide polymorphism at 6q25.1,rs2046210, with endometrial cancer risk among Chinese women

A recent genome-wide association study identified a new susceptibility locus for breast cancer, rs2046210, which is a single nucleotide polymorphism (SNP) located upstream of the estrogen receptor α (ESR1) gene on chromosome 6q25.1. Given that endometrial cancer shares many risk factors with breast cancer and both are related to estrogen exposure and that rs2046210 is in close proximity to the ESR1 gene, we evaluated the association of SNP rs2046210 with endometrial cancer risk among 953 cases and 947 contr...     

A single-nucleotide polymorphism in the methylene tetrahydrofolate reductase (MTHFR) gene is associated with risk of radiation pneumonitis in lung cancer patients treated with thoracic radiation therapy

BACKGROUND:

This study examined the association between functional single‐nucleotide polymorphisms in candidate genes from oxidative stress pathways and risk of radiation pneumonitis (RP) in patients treated with thoracic radiation therapy for locally advanced lung cancer.

METHODS:

A review was conducted of 136 patients treated with radiation therapy for lung cancer between 2001 and 2007, and who had prior genotyping of functional single‐nucleotide polymorphisms in oxidative stress genes including superoxide dismutase 2 (SOD2; rs4880) and methylene tetrahydrofolate reductase (MTHFR; rs1801131, rs1801133). RP events were retrospectively scored using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Cox proportional hazard regression was performed to identify clinical variables and genotypes associated with risk of RP of grades ≥2 and ≥3 on univariate and multivariate analysis, respectively. P values were corrected for multiple hypothesis esting.

RESULTS:

With a median follow‐up of 21.4 months, the incidence of grade ≥2 RP was 29% and grade ≥3 RP was 14%. On multivariate analysis, after adjusting for clinical factors such as concurrent chemotherapy and consolidation docetaxel, and lung dosimetric parameters such as volume receiving greater than 20 Gy and mean lung dose, MTHFR genotype (rs1801131; AA versus AC/CC) was significantly associated with risk of grade ≥2 RP (hazard ratio: 0.37; 95% confidence interval: 0.18‐0.76; P = .006, corrected P = .018) and grade ≥3 RP (hazard ratio: 0.21; 95% confidence interval: 0.06‐0.70; P = .01; corrected P = .03). SOD2 genotype was not associated with RP.

CONCLUSIONS:

This study showed an association between MTHFR genotype and risk of clinically significant RP. Further study of MTHFR‐related pathways may provide insight into the mechanisms behind RP. Cancer 2012;3654–3665. © 2011 American Cancer Society.