Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In West Bengal, India more than 6 million people are exposed to high levels of arsenic through drinking water. Since, only 15-20% of the exposed individuals show arsenic-induced skin lesions, it is assumed that genetic variation might play an important role in arsenic toxicity and carcinogenicity. Arsenic exposure often leads to the development of hyperkeratosis, the precursor of arsenic-induced skin cancer. ERCC2 (excision repair cross-complementing rodent repair deficiency, complementation group 2) is a nucleotide excision repair pathway gene, and its SNPs have been implicated in several types of epithelial cancers. We investigated the possible association of ERCC2 codon 751 A-->C polymorphism (lysine to glutamine) with arsenic-induced hyperkeratosis and correlated ERCC2 genotypes with increased frequencies of chromosomal aberration to ascertain whether any genotype leads to sub-optimal DNA repair. For this association study, 318 unrelated arsenic exposed subjects (165 with hyperkeratosis and 153 without any arsenic-induced skin lesions), drinking water contaminated with arsenic to a similar extent, were recruited. Genotyping was done through PCR-RFLP procedure. Lys/Lys genotype was significantly over-represented in the arsenic-induced hyperkeratosis-exhibiting group [odds ratio (OR) = 4.77, 95% confidence interval (CI) = 2.75-8.23]. A statistically significant increase in both CA/cell and percentage of aberrant cells was observed in the individuals with AA genotype compared to those with AC or CC genotype combined (P < 0.01) in each of the two study groups, as also, in the total study population. This study indicates that ERCC2 codon 751 Lys/Lys genotype is significantly associated with arsenic-induced premalignant hyperkeratosis and is possibly due to sub-optimal DNA repair capacity of the ERCC2 codon 751 Lys/Lys genotype.
Carcinogenesis 2007 Mar
PMID:Polymorphism in the ERCC2 codon 751 is associated with arsenic-induced premalignant hyperkeratosis and significant chromosome aberrations. 1705 May 53

DNA repair genes have been proposed as candidate cancer susceptibility genes. The excision repair cross-complementing rodent repair deficiency, complementation group 2 (ERCC2)/xeroderma pigmentosum complementary group D (XPD) protein is considered to be a key enzyme in nucleotide excision repair (NER) pathway. To elucidate whether common ERCC2 variants are associated with lung cancer susceptibility, we conducted a case-control study consisting of 339 cases with primary lung cancer and 358 controls matched on age, gender and ethnicity in a Chinese population. Six haplotype tagging single-nucleotide polymorphisms (htSNPs) (rs238403, rs50871, rs3916840, rs238415, rs3916874 and rs1799787) from HapMap database were analyzed, which provide an almost complete coverage of the genetic variations in the ERCC2 gene. Although none of the six htSNPs was individually associated with lung cancer risk, we found that two ERCC2 haplotypes were associated with risk of lung cancer. Haplotype 4 defined by rs238403T-rs50871T-rs3916840C-rs238415C-rs3916874G-rs1799787C and haplotype 7 defined by rs238403C-rs50871G-rs3916840C-rs238415C-rs3916874G-rs1799787C were strongly associated with an increased risk of lung cancer [odds ratio, OR (95% confidence interval, CI) = 2.62 (1.53-4.50), P = 0.0003 for hap4; OR (95% CI) = 3.01 (1.36-6.63), P = 0.004 for hap7]. Furthermore, diplotype analyses also strengthened the significant associations of risk haplotype 4 [OR (95% CI) = 3.56 (2.12-5.87), P < 0.001] or risk haplotype 7 [OR (95% CI) = 3.38 (1.75-6.55), P < 0.001] and lung cancer. Analysis of linkage disequilibrium (LD) also confirmed that considerable LD exists between the pairs of the six htSNPs within ERCC2. These results suggested that the risk subhaplotypes cosegregate with one or more biologically functional polymorphisms. Our results provide evidence to support a role for ERCC2 in lung cancer development in a Chinese population.
Carcinogenesis 2009 Jul
PMID:HapMap-based study of the DNA repair gene ERCC2 and lung cancer susceptibility in a Chinese population. 1940 34

DNA repair genes are important in maintaining genomic stability and integrity. DNA repair gene polymorphisms, such as those of the human homolog of 8-oxoguanine DNA glycosylase 1 (hOGG1) and excision repair cross-complementing rodent repair deficiency, complementation group 2/Xeroderma pigmentosum complementation group D (ERCC2/XPD), contribute to carcinogenesis. The aim of this study was to investigate the association of prostate cancer (PCa) risk with hOGG1 and ERCC2/XPD genetic variants. A case-control study of 200 cases including 100 PCa patients and 100 healthy subjects was conducted. Two single-nucleotide polymorphisms (SNPs) (ERCC2/XPD Arg156Arg and hOGG1 Ser326Cys) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results demonstrated a significant association of the XPD156 homozygous (AA, OR=3.80; 95% CI: 1.19-12.18; P=0.017), heterozygous (AC, OR=2.48; 95% CI: 1.02-6.35; P=0.033) and combined (AA+AC, OR=2.76; 95% CI: 1.18-6.84; P=0.011) mutant genotypes with a predisposition to high-risk PCa. In the stratified analysis, predisposition to high-risk PCa was also associated with the mutant genotypes of hOGG1 326 homozygous mutant (GG, OR=2.93; 95% CI: 1-8.74; P=0.033). The results also showed that the A allele of XPD Arg156Arg and the G allele of hOGG1 Ser326Cys were associated with an increased risk of PCa (OR=1.86 and 1.62; 95% CI: 1.13-3.06 and 1-2.67, respectively). In conclusion, the findings of this study demonstrated that the ERCC2/XPD Arg156Arg and hOGG1 Ser326Cys polymorphisms increased the susceptibility to high-risk PCa.
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PMID:Susceptibility of XPD and hOGG1 genetic variants to prostate cancer. 2464 9