Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.5.1.1 (DNA ligase)
 2,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

DNA repair enzyme genetic polymorphisms have been postulated to increase the risk of certain cancers in the presence of tobacco carcinogen exposures. The XPD protein is an important component of the TFIIH transcription factor complex. XPD genetic polymorphisms resulting in amino acids substitutions may lead to alterations in TFIIH helicase activity, resulting in repair and transcription defects. Cyclin D1 is a key regulatory protein for the transition of cells from the G(1)-S cell cycle phase. The CCND1 G870A polymorphism has been reported to enhance alternate splicing of a stable mRNA variant, which may result in the bypass of the G(1)/S cell cycle checkpoint. In this study, XPD G23591A (Asp312Asn) and A35931C (Lys751Gln) polymorphisms and the CCND1 G870A splice variant frequencies were determined in 273 upper aero-digestive tract cancer cases and 269 controls. The XPD Asp312Asn variant frequency was significantly different among cases and controls and conferred an odds ratio (OR) of 1.3 (95% CI 1.0-1.8). However, individuals with the CCND1 G870A and XPD Lys751Gln variants had higher age adjusted ORs of 3.2 (95% CI 2.2-4.6) and 2.2 (95% CI 1.5-3.2), respectively. Furthermore, a significant gene-gene interaction was observed among cases with at least two variant alleles for both CCND1 and XPD genes [OR 7.09 (95% CI 4.03-12.5)]. Smokers with a combination of at least one variant allele of both CCND1 and XPD genes also had an elevated risk as compared to nonsmokers. This is the first study to suggest an associative interaction between XPD and CCND1 genetic polymorphisms, tobacco exposure, and cancer risk.
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PMID:Association of polymorphisms in the cyclin D1 and XPD genes and susceptibility to cancers of the upper aero-digestive tract. 1575 15

Genetic variants in DNA repair enzymes contribute to the susceptibility to cutaneous melanoma; consequently, we analyzed whether common nonsynonymous single-nucleotide polymorphisms in DNA repair enzyme genes might also influence the course of disease. To this end, we determined eight polymorphisms of seven different DNA repair enzymes in 742 patients with cutaneous melanoma, and correlated these with overall survival. Univariate Cox proportional hazards model analyses revealed that ERCC5 (XPG) 1104 His/His was significantly associated with impaired survival. Indeed, the univariate hazard ratio (HR) was 2.8 times higher for patients with ERCC5 1104 His/His (P<0.001) compared with ERCC5 1104 Asp/Asp. Accordingly, the 5-year survival rate was 55% (95% confidence interval 43-71) for patients with ERCC5 1104 His/His, whereas 82% (95% confidence interval 78-86) of patients with ERCC5 1104 Asp/Asp were still alive at this time. Importantly, adjusted Cox regression analysis not only confirmed ERCC5 1104 His/His as an independent prognostic factor (multivariate HR=4.5; P<0.001), but also revealed the significant impact of ERCC2 (XPD) 751 Gln/Gln on prognosis, with a 2.2-fold increased HR compared with ERCC2 751 Lys/Lys (P=0.009). Thus, ERCC5 codon 1104 and ERCC2 codon 751 polymorphisms are independent prognostic factors in patients with cutaneous melanoma.
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PMID:ERCC5 p.Asp1104His and ERCC2 p.Lys751Gln polymorphisms are independent prognostic factors for the clinical course of melanoma. 2139 47

The effect of genetic polymorphism of DNA repair enzyme on the DNA adduct levels was evaluated in this study. We explored the relationship between polymorphism in the nucleotide excision repair enzyme XPD and DNA adduct levels in lymphocytes. Lymphocyte DNA adducts were measured by a (32.)
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PMID:Lymphocyte DNA adducts and polymorphism in the DNA repair enzyme XPD. 2388 80


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