Determinants and consequences of arsenic metabolism efficiency among 4,794 individuals: Demographics, lifestyle, genetics, and toxicity

Rick J. Jansen, Maria Argos, Lin Tong, Jiabei Li, Muhammad Rakibuz-Zaman, Md Tariqul Islam, Vesna Slavkovich, Alauddin Ahmed, Ana Navas-Acien, Faruque Parvez, Yu Chen, Mary V. Gamble, Joseph H. Graziano, Brandon L. Pierce, Habibul Ahsan

Research output: Contribution to journalArticlepeer-review

60 Scopus citations


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 toMMA(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.

Original languageEnglish (US)
Pages (from-to)381-390
Number of pages10
JournalCancer Epidemiology Biomarkers and Prevention
Issue number2
StatePublished - Feb 2016
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2015 American Association for Cancer Research.


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