التفاصيل البيبلوغرافية
| العنوان: |
Associations between arsenic (+3 oxidation state) methyltransferase (AS3MT) and N‐6 adenine‐specific DNA methyltransferase 1 (N6AMT1) polymorphisms, arsenic metabolism, and cancer risk in a chilean population |
| المؤلفون: |
de la Rosa, Rosemarie, Steinmaus, Craig, Akers, Nicholas K, Conde, Lucia, Ferreccio, Catterina, Kalman, David, Zhang, Kevin R, Skibola, Christine F, Smith, Allan H, Zhang, Luoping, Smith, Martyn T |
| المصدر: |
Environmental and Molecular Mutagenesis, vol 58, iss 6 |
| بيانات النشر: |
eScholarship, University of California |
| سنة النشر: |
2017 |
| المجموعة: |
University of California: eScholarship |
| مصطلحات موضوعية: |
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Oncology and Carcinogenesis, Cancer, Urologic Diseases, Clinical Research, Foodborne Illness, 2.1 Biological and endogenous factors, Aetiology, Aged, Arsenic, Chile, Female, Gene Frequency, Genetic Predisposition to Disease, Humans, Linkage Disequilibrium, Male, Methyltransferases, Middle Aged, Neoplasms, Oxidation-Reduction, Polymorphism, Genetic, Risk Factors, Site-Specific DNA-Methyltransferase (Adenine-Specific), Treatment Outcome, arsenic metabolism, N6AMT1 |
| جغرافية الموضوع: |
411 - 422 |
| الوصف: |
Inter-individual differences in arsenic metabolism have been linked to arsenic-related disease risks. Arsenic (+3) methyltransferase (AS3MT) is the primary enzyme involved in arsenic metabolism, and we previously demonstrated in vitro that N-6 adenine-specific DNA methyltransferase 1 (N6AMT1) also methylates the toxic inorganic arsenic (iAs) metabolite, monomethylarsonous acid (MMA), to the less toxic dimethylarsonic acid (DMA). Here, we evaluated whether AS3MT and N6AMT1 gene polymorphisms alter arsenic methylation and impact iAs-related cancer risks. We assessed AS3MT and N6AMT1 polymorphisms and urinary arsenic metabolites (%iAs, %MMA, %DMA) in 722 subjects from an arsenic-cancer case-control study in a uniquely exposed area in northern Chile. Polymorphisms were genotyped using a custom designed multiplex, ligation-dependent probe amplification (MLPA) assay for 6 AS3MT SNPs and 14 tag SNPs in the N6AMT1 gene. We found several AS3MT polymorphisms associated with both urinary arsenic metabolite profiles and cancer risk. For example, compared to wildtypes, individuals carrying minor alleles in AS3MT rs3740393 had lower %MMA (mean difference = -1.9%, 95% CI: -3.3, -0.4), higher %DMA (mean difference = 4.0%, 95% CI: 1.5, 6.5), and lower odds ratios for bladder (OR = 0.3; 95% CI: 0.1-0.6) and lung cancer (OR = 0.6; 95% CI: 0.2-1.1). Evidence of interaction was also observed for both lung and bladder cancer between these polymorphisms and elevated historical arsenic exposures. Clear associations were not seen for N6AMT1. These results are the first to demonstrate a direct association between AS3MT polymorphisms and arsenic-related internal cancer risk. This research could help identify subpopulations that are particularly vulnerable to arsenic-related disease. Environ. Mol. Mutagen. 58:411-422, 2017. © 2017 Wiley Periodicals, Inc. |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
unknown |
| العلاقة: |
qt4js2b595; https://escholarship.org/uc/item/4js2b595Test |
| الإتاحة: |
https://escholarship.org/uc/item/4js2b595Test |
| حقوق: |
public |
| رقم الانضمام: |
edsbas.B158ED2C |
| قاعدة البيانات: |
BASE |
