Carcinogenesis Advance Access originally published online on October 17, 2006
Carcinogenesis 2007 28(3):672-676; doi:10.1093/carcin/bgl181
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Polymorphism in the ERCC2 codon 751 is associated with arsenic-induced premalignant hyperkeratosis and significant chromosome aberrations
1 Molecular and Human Genetics Division, Indian Institute of Chemical Biology Kolkata, India
2 West Bank Hospital, Howrah India
3 Vivekananda Institute of Medical Sciences, Kolkata India
4 Peerless Hospital and B.K Roy Research Centre Kolkata, India
5 Regional Institute of Ophthalmology, Calcutta Medical College Kolkata, India
*To whom correspondence should be addressed at: Molecular and Human Genetics Division, Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Jadavpur, Kolkata 700 032, India Tel: +91 33 2473 3491/0492/6793; Fax: +91 33 2473 5197; E-mail: akgiri15{at}yahoo.com; akgiri{at}iicb.res.in
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.
Abbreviations: CA, chromosomal aberrations; ERCC2, excision repair cross-complementing rodent repair deficiency, complementation group 2; NER, nucleotide excision repair; XPD, xeroderma pigmentosum group D
Received June 30, 2006; revised September 13, 2006; accepted September 20, 2006.
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