TY - JOUR
T1 - 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
AU - Seow, Wei Jie
AU - Pan, Wen Chi
AU - Kile, Molly L.
AU - Tong, Lin
AU - Baccarelli, Andrea A.
AU - Quamruzzaman, Quazi
AU - Rahman, Mahmuder
AU - Mostofa, Golam
AU - Rakibuz-Zaman, Muhammad
AU - Kibriya, Muhammad
AU - Ahsan, Habibul
AU - Lin, Xihong
AU - Christiani, David C.
N1 - Publisher Copyright:
© 2015 American Cancer Society. © 2015 American Cancer Society.
PY - 2015/7/1
Y1 - 2015/7/1
N2 - 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. Cancer 2015;121:2222-2229.
AB - 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. Cancer 2015;121:2222-2229.
KW - arsenic
KW - environmental health
KW - genetic polymorphisms
KW - skin cancer
KW - susceptibility
UR - http://www.scopus.com/inward/record.url?scp=84931561149&partnerID=8YFLogxK
U2 - 10.1002/cncr.29291
DO - 10.1002/cncr.29291
M3 - Article
C2 - 25759212
AN - SCOPUS:84931561149
SN - 0008-543X
VL - 121
SP - 2222
EP - 2229
JO - Cancer
JF - Cancer
IS - 13
ER -
