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Polymorphism in the ERCC2 codon 751 is Associated with Arsenic-Induced Premalignant Hyperkeratosis and Significant Chromosome Aberrations

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Title Polymorphism in the ERCC2 codon 751 is Associated with Arsenic-Induced Premalignant Hyperkeratosis and Significant Chromosome Aberrations
 
Creator Banerjee, Mayukh
Sarkar, Jyotirmoy
Das, Jayanta K
Mukhopadhyay, Angshuman
Sarkar, Ajoy K
Mondal, Lakshmikanta
Giri, Ashok K
 
Subject Molecular & Human Genetics
 
Description 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 arsenicinduced skin cancer. ERCC2 (excision repair crosscomplementing 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 correlatedERCC2 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) ¼ 4.77,
95% confidence interval (CI) ¼ 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.
 
Date 2007
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/1211/1/Carcinogenesis_Paper.pdf
Banerjee, Mayukh and Sarkar, Jyotirmoy and Das, Jayanta K and Mukhopadhyay, Angshuman and Sarkar, Ajoy K and Mondal, Lakshmikanta and Giri, Ashok K (2007) Polymorphism in the ERCC2 codon 751 is Associated with Arsenic-Induced Premalignant Hyperkeratosis and Significant Chromosome Aberrations. Carcinogenesis, 28 (3). pp. 672-676.
 
Relation http://dx.doi.org/10.1093/carcin/bgl181
http://www.eprints.iicb.res.in/1211/