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Cancer. 2015 Jul 1;121(13):2222-9. doi: 10.1002/cncr.29291. Epub 2015 Mar 10.

A distinct and replicable variant of the squamous cell carcinoma gene inositol polyphosphate-5-phosphatase modifies the susceptibility of arsenic-associated skin lesions in Bangladesh.

Author information

1
Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts.
2
College of Public Health and Human Sciences, Oregon State University, Corvallis, Oregon.
3
Department of Health Studies, University of Chicago, Chicago, Illinois.
4
Dhaka Community Hospital, Dhaka, Bangladesh.
5
UChicago Research Bangladesh, Dhaka, Bangladesh.
6
Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts.

Abstract

BACKGROUND:

Single-nucleotide polymorphisms (SNPs) in inflammation, one-carbon metabolism, and skin cancer genes might influence susceptibility to arsenic-induced skin lesions.

METHODS:

A case-control study was conducted in Pabna, Bangladesh (2001-2003), and the drinking-water arsenic concentration was measured for each participant. A panel of 25 candidate SNPs was analyzed in 540 cases and 400 controls. Logistic regression was used to estimate the association between each SNP and the potential for gene-environment interactions in the skin lesion risk, with adjustments for relevant covariates. Replication testing was conducted in an independent Bangladesh population with 488 cases and 2,794 controls.

RESULTS:

In the discovery population, genetic variants in the one-carbon metabolism genes phosphatidylethanolamine N-methyltransferase (rs2278952, P for interaction  = .004; rs897453, P for interaction = .05) and dihydrofolate reductase (rs1650697, P for interaction = .02), the inflammation gene interleukin 10 (rs3024496, P for interaction =.04), and the skin cancer genes inositol polyphosphate-5-phosphatase (INPP5A; rs1133400, P for interaction = .03) and xeroderma pigmentosum complementation group C (rs2228000, P for interaction = .01) significantly modified the association between arsenic and skin lesions after adjustments for multiple comparisons. The significant gene-environment interaction between a SNP in the INPP5A gene (rs1133400) and water arsenic with respect to the skin lesion risk was successfully replicated in an independent population (P for interaction = .03).

CONCLUSIONS:

Minor allele carriers of the skin cancer gene INPP5A modified the odds of arsenic-induced skin lesions in both main and replicative populations. Genetic variation in INPP5A appears to have a role in susceptibility to arsenic toxicity.

KEYWORDS:

arsenic; environmental health; genetic polymorphisms; skin cancer; susceptibility

PMID:
25759212
PMCID:
PMC4565788
DOI:
10.1002/cncr.29291
[Indexed for MEDLINE]
Free PMC Article

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