Dataset Information

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

ABSTRACT: 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 beta-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.

SUBMITTER: Steinmaus C

PROVIDER: S-EPMC3849353 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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

Steinmaus Craig C Yuan Yan Y Kalman Dave D Rey Omar A OA Skibola Christine F CF Dauphine Dave D Basu Anamika A Porter Kristin E KE Hubbard Alan A Bates Michael N MN Smith Martyn T MT Smith Allan H AH

Toxicology and applied pharmacology 20100617 2

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, Arg ...[more]

PMID: 20600216

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Project description:BACKGROUND:Hormonal therapy is an integral component for breast cancer treatment in women with oestrogen receptor positive tumours in early-stage and advanced cases of the disease. Little is known about what factors influence oncologists' prescribing practices, especially non-biological factors, although this information may have important implications for understanding inequalities in health care quality and outcomes. This paper presents findings from research on factors influencing oncologists' prescribing hormonal therapy for women with early and advanced cases of breast cancer in the city of Córdoba, Argentina. METHODS:A qualitative study using in-depth, semi-structured interviews with 16 oncologists was conducted. A stratified purposive sampling was used to recruit female and male participants and working at 3 health subsystems (private, social security, public). Data was analysed using the Framework approach. RESULTS:According to the respondents, factors influencing prescribing practices of hormonal therapy are varied. Women's socio-economic status (poverty and wealth) and their level of health literacy can affect oncologists' prescribing practices. Overall, in comparison to male, female oncologists reported more awareness of patients' needs, more involvement in communicating drug side-effects, and in offering treatment options in private health settings. The 3 health subsystems provided a differential access to drugs and lines of hormonal treatment, which ranged from a limited availability in the public sector, to administrative restrictions imposed by the social security system, and to a lesser extent, the private sector. This happened in the backdrop of national legislation covering oncological treatments and drugs free of charge. CONCLUSIONS:Addressing prescribing practices for hormonal therapy as a distinct type of breast cancer treatment (chronic care) is fundamental in the understanding of breast cancer care and can shed light on inequalities in treatments. Identifying the underlying care gaps in the prescription of hormonal therapy can help in the design of tailored interventions.

Project description:Biomethylation is the major pathway for the metabolism of inorganic arsenic (iAs) in many mammalian species, including the human. However, significant interspecies differences have been reported in the rate of in vivo metabolism of iAs and in yields of iAs metabolites found in urine. Liver is considered the primary site for the methylation of iAs and arsenic (+3 oxidation state) methyltransferase (As3mt) is the key enzyme in this pathway. Thus, the As3mt-catalyzed methylation of iAs in the liver determines in part the rate and the pattern of iAs metabolism in various species. We examined kinetics and concentration-response patterns for iAs methylation by cultured primary hepatocytes derived from human, rat, mice, dog, rabbit, and rhesus monkey. Hepatocytes were exposed to [(73)As]arsenite (iAs(III); 0.3, 0.9, 3.0, 9.0 or 30 nmol As/mg protein) for 24 h and radiolabeled metabolites were analyzed in cells and culture media. Hepatocytes from all six species methylated iAs(III) to methylarsenic (MAs) and dimethylarsenic (DMAs). Notably, dog, rat and monkey hepatocytes were considerably more efficient methylators of iAs(III) than mouse, rabbit or human hepatocytes. The low efficiency of mouse, rabbit and human hepatocytes to methylate iAs(III) was associated with inhibition of DMAs production by moderate concentrations of iAs(III) and with retention of iAs and MAs in cells. No significant correlations were found between the rate of iAs methylation and the thioredoxin reductase activity or glutathione concentration, two factors that modulate the activity of recombinant As3mt. No associations between the rates of iAs methylation and As3mt protein structures were found for the six species examined. Immunoblot analyses indicate that the superior arsenic methylation capacities of dog, rat and monkey hepatocytes examined in this study may be associated with a higher As3mt expression. However, factors other than As3mt expression may also contribute to the interspecies differences in the hepatocyte capacity to methylate iAs.

Dataset Information

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

Publications

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

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