中国辽宁汉族群体DNA修复基因: ERCC2/XPD A35931C 遗传多态性

DNA修复基因在保护维持基因组整体性及抗癌发生过程中起着重要作用，DNA修复基因的产物:ERCC2/XPD参与核苷酸切除修复过程。单核苷酸多态的群体遗传学信息对于遗传疾病的研究是非常重要的。我们调查了中国辽宁汉族群体DNA修复基因: ERCC2 A35931C 遗传多态性。ERCC2 A35931C基因型频率：AA=0.95; AC=0.05; CC=0, 基因型分布符合Hardy-Weinberg遗传平衡定律(P=0.77)；ERCC2 A35931C等位基因频率：A=0.98; C=0.02。研究结果与前期所报道的其他群体的该等位基因频率分布进行比较。     

DNA repair gene excision repair cross complementing-group 1 (ERCC1) in head and neck squamous cell carcinoma: analysis of methylation and polymorphism (G19007A), protein expression and association with epidemiological and clinicopathological factors

Lima L M C, de Souza L R, da Silva T F, Pereira C S, Guimarães A L S, de Paula A M B & Carvalho H A
(2012) Histopathology  60, 489–496
DNA repair gene excision repair cross complementing‐group 1 (ERCC1) in head and neck squamous cell carcinoma: analysis of methylation and polymorphism (G19007A), protein expression and association with epidemiological and clinicopathological factors Aims: To evaluate the associations of excision repair cross complementing‐group 1 (ERCC1) (DNA repair protein) (G19007A) polymorphism, methylation and immunohistochemical expression with epidemiological and clinicopathological factors and with overall survival in head and neck squamous cell carcinoma (HNSCC) patients. Methods and results: The study group comprised 84 patients with HNSCC who underwent surgery and adjuvant radiotherapy without chemotherapy. Bivariate and multivariate analyses were used. The allele A genotype variant was observed in 79.8% of the samples, GG in 20.2%, GA in 28.6% and AA in 51.2%. Individuals aged more than 45 years had a higher prevalence of the allelic A variant and a high (83.3%) immunohistochemical expression of ERCC1 protein [odds ratio (OR) = 4.86, 95% confidence interval (CI): 1.2–19.7, P = 0.027], which was also high in patients with advanced stage (OR=5.04, 95% CI: 1.07–23.7, P = 0.041). Methylated status was found in 51.2% of the samples, and was higher in patients who did not present distant metastasis (OR = 6.67, 95% CI: 1.40–33.33, P = 0.019) and in patients with advanced stage (OR = 5.04, 95% CI: 1.07–23.7, P = 0.041). At 2 and 5 years, overall survival was 55% and 36%, respectively (median = 30 months). Conclusion: Our findings may reflect a high rate of DNA repair due to frequent tissue injury during the lifetime of these individuals, and also more advanced disease presentation in this population with worse prognosis.     

Germ line mutations of hMSH2 and hMLH1 genes in Japanese families with hereditary nonpolyposis colorectal cancer (HNPCC): usefulness of DNA analysis for screening and diagnosis of HNPCC patients

Mutations in hMSH2 and hMLH1 genes were analyzed in patients from 11 Japanese families that had been diagnosed as carrying hereditary nonpolyposis colorectal cancer (HNPCC) by clinical examination. Germ line mutations of hMSH2 gene were identified in 5 independent families in which colorectal (87% of patients), endometrial (30%), ovarian (17%), gastric (14%), and other cancers existed. Five mutations detected between codons 136 and 811 included single-base substitutions (CT and TG), a T deletion, and an A insertion, all of which produced stop codons resulting in truncated proteins, and an AT substitution at splice donor site of exon 5 which resulted in deletion of this exon. Moreover, one HNPCC family was presumed to have germ line mutation of hMSH2 gene because a somatic mutation of hMSH2 gene was detected in a cancer from a patient in this family. In addition to these 11 families already diagnosed with HNPCC, 3 new families with germ line mutations of hMSH2 gene and hMLH1 gene were found through analysis of DNA from patients who had multiple cancers with alteration in microsatellite DNA. These mutations included an AG deletion at codons 877–878 of hMSH2 gene, an AAG deletion at codons 616–618 of hMLH1 gene, and a CT single-base substitution at codon 217 of hMLH1 gene. Seven of eight germ line mutations found in this study are new mutations that have not been reported previously. In families in which germ line mutations were identified presymptomatic examination was then carried out using polymerase chain reaction single-strand conformation polymorphism analysis of DNA from peripheral blood, and the result was the detection of family members predisposed to HNPCC who did not yet show signs of cancer. These results indicate the value of DNA analysis in the screening and diagnosis of HNPCC patients and families.Abbreviations HNPCC Hereditary nonpolyposis colorectal cancer - PCR Polymerase chain reaction - SSCP Single-strand conformation polymorphism