Individual differences in arsenic metabolism and lung cancer in a case-control study in Cordoba, Argentina

In humans, ingested inorganic arsenic is metabolized to monomethylarsenic (MMA) then to dimethylarsenic (DMA), although in most people this process is not complete. Previous studies have identified associations between the proportion of urinary MMA (%MMA) and increased risks of several arsenic-relat...

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Bibliographic Details
Published in:	Toxicology and applied pharmacology Vol. 247; no. 2; pp. 138 - 145
Main Authors:	Steinmaus, Craig, Yuan, Yan, Kalman, Dave, Rey, Omar A., Skibola, Christine F., Dauphine, Dave, Basu, Anamika, Porter, Kristin E., Hubbard, Alan, Bates, Michael N., Smith, Martyn T., Smith, Allan H.
Format:	Journal Article
Language:	English
Published:	Amsterdam Elsevier Inc 01-09-2010 Elsevier
Subjects:	60 APPLIED LIFE SCIENCES Adult Aged Aged, 80 and over Argentina ARSENIC Arsenic - urine Biological and medical sciences BODY Carcinogenesis, carcinogens and anticarcinogens Case-Control Studies Chemical agents Chemical and industrial products toxicology. Toxic occupational diseases Cystathionine beta-Synthase - genetics DISEASES DRINKING WATER ELEMENTS Environmental Exposure - statistics & numerical data Female Humans HYDROGEN COMPOUNDS Lung cancer Lung Neoplasms - epidemiology Lung Neoplasms - genetics Lung Neoplasms - urine LUNGS Male Medical sciences METABOLISM Metals and various inorganic compounds Middle Aged NEOPLASMS ORGANS OXYGEN COMPOUNDS Pneumology RADIOLOGY AND NUCLEAR MEDICINE RESPIRATORY SYSTEM Risk Factors SEMIMETALS Toxicology Tumors Tumors of the respiratory system and mediastinum WATER Young Adult South America Argentina America Drinking water Arsenic Metabolism Lung cancer Human Lung disease Respiratory disease Malignant tumor Case control study Bronchopulmonary Carcinogen Bronchus disease Cancer
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Summary:	In humans, ingested inorganic arsenic is metabolized to monomethylarsenic (MMA) then to dimethylarsenic (DMA), although in most people this process is not complete. Previous studies have identified associations between the proportion of urinary MMA (%MMA) and increased risks of several arsenic-related diseases, although none of these reported on lung cancer. In this study, urinary arsenic metabolites were assessed in 45 lung cancer cases and 75 controls from arsenic-exposed areas in Cordoba, Argentina. Folate has also been linked to arsenic-disease susceptibility, thus an exploratory assessment of associations between single nucleotide polymorphisms in folate metabolizing genes, arsenic methylation, and lung cancer was also conducted. In analyses limited to subjects with metabolite concentrations above detection limits, the mean %MMA was higher in cases than in controls (17.5% versus 14.3%, p = 0.01). The lung cancer odds ratio for subjects with %MMA in the upper tertile compared to those in the lowest tertile was 3.09 (95% CI, 1.08–8.81). Although the study size was too small for a definitive conclusion, there was an indication that lung cancer risks might be highest in those with a high %MMA who also carried cystathionine β-synthase ( CBS) rs234709 and rs4920037 variant alleles. This study is the first to report an association between individual differences in arsenic metabolism and lung cancer, a leading cause of arsenic-related mortality. These results add to the increasing body of evidence that variation in arsenic metabolism plays an important role in arsenic-disease susceptibility.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	0041-008X 1096-0333
DOI:	10.1016/j.taap.2010.06.006