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Cancer Epidemiol Biomarkers Prev. 2016 Feb;25(2):381-90. doi: 10.1158/1055-9965.EPI-15-0718. Epub 2015 Dec 16.

Determinants and Consequences of Arsenic Metabolism Efficiency among 4,794 Individuals: Demographics, Lifestyle, Genetics, and Toxicity.

Author information

1
Department of Public Health Sciences, The University of Chicago, Chicago, Illinois.
2
Divison of Epidemiology and Biostatistics, School of Public Health, University of Illinois at Chicago, Chicago, Illinois.
3
UChicago Research Bangladesh, Dhaka, Bangladesh.
4
Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York.
5
Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
6
Departments of Population Health and Environmental Medicine, New York University School of Medicine, New York, New York.
7
Department of Public Health Sciences, The University of Chicago, Chicago, Illinois. Department of Human Genetics and Comprehensive Cancer Center, The University of Chicago, Chicago, Illinois. brandonpierce@uchicago.edu habib@uchicago.edu.
8
Department of Public Health Sciences, The University of Chicago, Chicago, Illinois. Department of Human Genetics and Comprehensive Cancer Center, The University of Chicago, Chicago, Illinois. Department of Medicine, The University of Chicago, Chicago, Illinois. brandonpierce@uchicago.edu habib@uchicago.edu.

Abstract

BACKGROUND:

Exposure to inorganic arsenic (iAs), a class I carcinogen, affects several hundred million people worldwide. Once absorbed, iAs is converted to monomethylated (MMA) and then dimethylated forms (DMA), with methylation facilitating urinary excretion. The abundance of each species in urine relative to their sum (iAs%, MMA%, and DMA%) varies across individuals, reflecting differences in arsenic metabolism capacity.

METHODS:

The association of arsenic metabolism phenotypes with participant characteristics and arsenical skin lesions was characterized among 4,794 participants in the Health Effects of Arsenic Longitudinal Study (Araihazar, Bangladesh). Metabolism phenotypes include those obtained from principal component (PC) analysis of arsenic species.

RESULTS:

Two independent PCs were identified: PC1 appears to represent capacity to produce DMA (second methylation step), and PC2 appears to represent capacity to convert iAs to MMA (first methylation step). PC1 was positively associated (P <0.05) with age, female sex, and BMI, while negatively associated with smoking, arsenic exposure, education, and land ownership. PC2 was positively associated with age and education but negatively associated with female sex and BMI. PC2 was positively associated with skin lesion status, while PC1 was not. 10q24.32/AS3MT region polymorphisms were strongly associated with PC1, but not PC2. Patterns of association for most variables were similar for PC1 and DMA%, and for PC2 and MMA% with the exception of arsenic exposure and SNP associations.

CONCLUSIONS:

Two distinct arsenic metabolism phenotypes show unique associations with age, sex, BMI, 10q24.32 polymorphisms, and skin lesions.

IMPACT:

This work enhances our understanding of arsenic metabolism kinetics and toxicity risk profiles.

PMID:
26677206
PMCID:
PMC4767610
DOI:
10.1158/1055-9965.EPI-15-0718
[Indexed for MEDLINE]
Free PMC Article

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