DNA Repair Capacity-Related to Genetic Polymorphisms of DNA Repair Genes and Aflatoxin B1-Related Hepatocellular Carcinoma Among Chinese Population

4039 Background: Polymorphisms in the DNA repair genes may contribute to variation in DNA repair capacity, thereby affecting the risk of carcinogenesis and prognosis of colorectal cancer. Accordingly, the present study analyzed polymorphisms of DNA repair genes and their impact on the prognosis for patients with colorectal cancer. Methods: Three hundred and ninety- seven consecutive patients with curatively resected colorectal adenocarcinoma were enrolled in the present study. The genomic DNA was extracted from fresh colorectal tissue and 14 polymorphisms of DNA repair genes (XRCC1, hMLH1, ERCC2, ERCC4, VARS2[rs2074511, rs2249459], XPA, XPC, POLR2A, POLR2B, RFC1, RFC4, XAB2, DNMT3B) determined using a PCR-RFLP assay. Results: The median age of the patients was 63 years (range, 21–85), and 218 (54.9%) patients had colon cancer and 179 (45.1%) patients rectal cancer. Pathologic stages after surgery were as follows: stage 0/I (n=86, 21.7%), stage II (n=146, 36.8%), stage III (n=145, 36.5%), and stage IV (n=20, 5.0%). Multivariate survival analysis including stage, differentiation, age, and CEA level showed that the survival for the patients with the -93AA genotype of hMLH1 was worse than for the patients with the combined -93GG and GA genotype (overall survival: hazard ratio [HR]=2.953, 95% Confidential Interval [CI], 1.273–6.850, P=0.012; disease-free survival: HR=2.299, 95% CI, 1.417–3.730, P=0.001), whereas the other polymorphisms were not associated with survival. Conclusions: The -93G>A polymorphism of hMLH1 was found to be an independent prognostic marker for patients with colorectal cancer. Accordingly, in addition to the pathologic stage, the analysis of -93G>A polymorphism of hMLH1 can help identify patient subgroups at high risk of a poor disease outcome. No significant financial relationships to disclose.

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Genetic manipulation in Sulfolobus islandicus and functional analysis of DNA repair genes

Biochemical Society Transactions ◽

10.1042/bst20120285 ◽

2013 ◽

Vol 41 (1) ◽

pp. 405-410 ◽

Cited By ~ 49

Author(s):

Changyi Zhang ◽

Bin Tian ◽

Suming Li ◽

Xiang Ao ◽

Kevin Dalgaard ◽

...

Keyword(s):

Dna Repair ◽

Genetic Manipulation ◽

Excision Repair ◽

Model Organism ◽

Dna Repair Genes ◽

Repair Capacity ◽

Dna Repair Capacity ◽

Sulfolobus Islandicus ◽

Base Excision ◽

Repair Genes

Recently, a novel gene-deletion method was developed for the crenarchaeal model Sulfolobus islandicus, which is a suitable tool for addressing gene essentiality in depth. Using this technique, we have investigated functions of putative DNA repair genes by constructing deletion mutants and studying their phenotype. We found that this archaeon may not encode a eukarya-type of NER (nucleotide excision repair) pathway because depleting each of the eukaryal NER homologues XPD, XPB and XPF did not impair the DNA repair capacity in their mutants. However, among seven homologous recombination proteins, including RadA, Hel308/Hjm, Rad50, Mre11, HerA, NurA and Hjc, only the Hjc nuclease is dispensable for cell viability. Sulfolobus encodes redundant BER (base excision repair) enzymes such as two uracil DNA glycosylases and two putative apurinic/apyrimidinic lyases, but inactivation of one of the redundant enzymes already impaired cell growth, highlighting their important roles in archaeal DNA repair. Systematically characterizing these mutants and generating mutants lacking two or more DNA repair genes will yield further insights into the genetic mechanisms of DNA repair in this model organism.

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The genotype distribution of the XRCC1gene indicates a role for base excision repair in the development of therapy-related acute myeloblastic leukemia

Blood ◽

10.1182/blood-2002-04-1152 ◽

2002 ◽

Vol 100 (10) ◽

pp. 3761-3766 ◽

Cited By ~ 118

Author(s):

Claire Seedhouse ◽

Rowena Bainton ◽

Michael Lewis ◽

Alexander Harding ◽

Nigel Russell ◽

...

Keyword(s):

Dna Repair ◽

Protective Effect ◽

Excision Repair ◽

Acute Myeloblastic Leukemia ◽

Polymorphism Analysis ◽

Genotype Distribution ◽

Dna Repair Genes ◽

Repair Capacity ◽

Dna Repair Capacity ◽

Repair Genes

Polymorphisms in several DNA repair genes have been described. These polymorphisms may affect DNA repair capacity and modulate cancer susceptibility by means of gene-environment interactions. We investigated DNA repair capacity and its association with acute myeloblastic leukemia (AML). We studied polymorphisms in 3 DNA repair genes: XRCC1, XRCC3, and XPD. We also assessed the incidence of a functional polymorphism in theNQO1 gene, which is involved in protection of cells from oxidative damage. We genotyped the polymorphisms by using polymerase chain reaction–restriction fragment-length polymorphism analysis in 134 patients with de novo AML, 34 with therapy-related AML (t-AML), and 178 controls. The distributions of theXRCC3 Thr241Met and NQO1 Pro187Ser genotypes were not significantly different in patients and controls. However, the distribution of the XRCC1 Arg399Gln genotypes was significantly different when comparing the t-AML and control groups (χ2, P = .03). The presence of at least oneXRCC1 399Gln allele indicated a protective effect for the allele in controls compared with patients with t-AML (odds ratio 0.44; 95% confidence interval, 0.20-0.93). We found no interactions between the XRCC1 or XRCC3 and NQO1genotypes. We also found no differences in the distribution of the XPD Lys751Gln or XRCC1 Arg194Trp genotypes. Our data provide evidence of a protective effect against AML in individuals with at least one copy of the variant XRCC1 399Gln allele compared with those homozygous for the common allele.

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