Polymorphism in the ERCC2 codon 751 is associated with arsenic-induced premalignant hyperkeratosis and significant chromosome aberrations

Banerjee, M; Sarkar, J; Das, JK; Mukherjee, A; Sarkar, AK; Mondal, L; Giri, AK

HERO ID

627579

Reference Type

Journal Article

Year

2007

Language

English

PMID

17050553

HERO ID 627579
In Press No
Year 2007
Title Polymorphism in the ERCC2 codon 751 is associated with arsenic-induced premalignant hyperkeratosis and significant chromosome aberrations
Authors Banerjee, M; Sarkar, J; Das, JK; Mukherjee, A; Sarkar, AK; Mondal, L; Giri, AK
Journal Carcinogenesis
Volume 28
Issue 3
Page Numbers 672-676
Abstract 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.
Doi 10.1093/carcin/bgl181
Pmid 17050553
Wosid WOS:000245351100018
Is Certified Translation No
Dupe Override No
Comments |WOS:000245351100018
Is Public Yes
Language Text English
Is Qa No