Carcinogenesis Advance Access published online on October 17, 2006
Carcinogenesis, doi:10.1093/carcin/bgl181
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1 Indian Institute of Chemical Biology, Kolkata, India
* To whom correspondence should be addressed. In West Bengal, India more than 6 million people are exposed to high levels of arsenic through drinking water. Since, only 15 to 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 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
Received June 30, 2006
Revised September 13, 2006
Accepted September 20, 2006
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Polymorphism in the ERCC2 codon 751 is associated with arsenic-induced premalignant hyperkeratosis and significant chromosome aberrations
Mayukh Banerjee 1, Jyotirmoy Sarkar 1, Jayanta K. Das 2, Angshuman Mukherjee 3, Ajoy K. Sarkar 4, Lakshmikanta Mondal 5, and Ashok K. Giri 1 *
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
Ashok K. Giri, E-mail: akgiri15{at}yahoo.com; akgiri@iicb.res.in
Abstract 
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. Three hundred eighteen unrelated arsenic exposed subjects (165 with hyperkeratosis and 153 without any arsenic-induced skin lesions), drinking water contaminated with arsenic to similar extent, were recruited for this association study. Genotyping was done through PCR-RFLP procedure. Lys/Lys genotype was significantly over represented in the arsenic-induced hyperkeratosis-exhibiting group (OR=4.77, 95% CI 2.75 to 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.
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