Arsenic occurs naturally in many environmental components and enters the human body through several exposure pathways. Natural enrichment of arsenic may result in considerable contamination of soil, water, and air. Arsenic in groundwater can exceed values hundreds of time higher than the concentration recommended for drinking water. Such exposure levels indicate a serious potential health risk to individuals consuming raw groundwater. Human activities that have an impact on the environment may increase the distribution of inorganic arsenic. Abandoned mines are of great concern due to the extremely high arsenic concentrations detected in mine drainage and tailings. Diet, drinking water, air, soil, and occupational exposures are all sources of inorganic arsenic for humans. Interdisciplinary efforts to better characterize the transport of arsenic and reactants that facilitate their release to the environment are important for human health studies. Multi-disciplinary efforts are needed to study diet, infectious disease, genetics, and cultural practices unique to each region to better understand human health risk and to design public health interventions.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) may increase breast cancer risk, and the association may be modified by inherited differences in deactivation of PAH intermediates by glutathione S-transferases (GSTs). Few breast cancer studies have investigated the joint effects of multiple GSTs and a PAH biomarker. OBJECTIVE: We estimated the breast cancer risk associated with multiple polymorphisms in the GST gene (GSTA1, GSTM1, GSTP1, and GSTT1) and the interaction with PAH-DNA adducts and cigarette smoking. METHODS: We conducted unconditional logistic regression using data from a population-based sample of women (cases/controls, respectively): GST polymorphisms were genotyped using polymerase chain reaction and matrix-assisted laser desorption/ionization time-of-flight assays (n = 926 of 916), PAH-DNA adduct blood levels were measured by competitive enzyme-linked immunosorbent assay (n = 873 of 941), and smoking status was assessed by in-person questionnaires (n = 943 of 973). RESULTS: Odds ratios for joint effects on breast cancer risk among women with at least three variant alleles were 1.56 [95% confidence interval (CI), 1.13-2.16] for detectable PAH-DNA adducts and 0.93 (95% CI, 0.56-1.56) for no detectable adducts; corresponding odds ratios for three or more variants were 1.18 (95% CI, 0.82-1.69) for ever smokers and 1.44 (95% CI, 0.97-2.14) for never smokers. Neither interaction was statistically significant (p = 0.43 and 0.62, respectively). CONCLUSION: We found little statistical evidence that PAHs interacted with GSTT1, GSTM1, GSTP1, and GSTA1 polymorphisms to further increase breast cancer risk.

Background: Single nucleotide polymorphisms in genes related to DNA repair capacity and UV exposure have not been well investigated in relation to skin lesions associated with arsenic exposure. This population based case-control study, of 600 cases and 600 controls, frequency matched on age and gender in Pabna, Bangladesh in 2001-2002, investigated the association and potential effect modification between polymorphisms in XPD (Lys751Gln and Asp312Asn) genes, tendency to sunburn and arsenic related skin lesions. Methods: Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Result: No significant association was observed between skin lesions and the XPD 312 Asp/Asn (AOR 0.87, 95%CI (0.65-1.15)) Asn/Asn (AOR 0.76, 95%CI (0.50-1.15))(referent Asp/Asp); XPD 751 Lys/Gln (AOR 0.92, 95% CI (0.69-1.23)) Gln/Gln (AOR 0.98, 95%CI (0.66-1.45))(referent Lys/Lys. While we did not observe any evidence of effect modification of these polymorphisms on the association between well arsenic concentration and skin lesions; we did observe effect modification between these polymorphisms and sunburn tendency and arsenic related skin lesions. Individuals with the heterozygote or homozygote variant forms (Asp/Asn or Asn/Asn) had half the risk of skin lesions (OR 0.45 95%CI 0.29-0.68) compared to those with the wild type XPDAsp312Asn genotype (Asp/Asp) and individuals with heterozygote or homozygote variant forms (Lys/Gln or Gln/Gln) had half the risk of skin lesions (OR 0.47 95%CI 0.31-0.72) compared to those with the wild type XPDLys751Gln genotype (Lys/Lys), within the least sensitive strata of sunburn severity. We observed effect modification on the multiplicative scale for XPD 751 and XPD 312. Conclusion: Tendency to sunburn modified the relationship between XPD polymorphism and skin lesions. Further study is necessary to explore the effect of XPD polymorphisms and sun exposure on risk of arsenic related skin lesions.

OBJECTIVE: We investigated whether primary and secondary arsenic methylation ratios were associated with skin lesions and whether GSTT1, GSTP1, and GSTM1 polymorphisms modify these relationships. METHODS: A case-control study of 600 cases and 600 controls that were frequency matched on age and sex was conducted in Pabna, Bangladesh, in 2001-2002. Individual well water, urine, and blood samples were collected. Water arsenic concentration was determined using inductively coupled plasma mass spectrometry (ICP-MS). Urinary arsenic speciation was determined using high performance liquid chromatography hydride with generator atomic absorption spectrometry and ICP-MS. Genotyping was conducted using multiplex polymerase chain reaction and TaqMan. RESULTS: A 10-fold increase in primary methylation ratio [monomethylarsonic acid (MMA)/(arsenite + arsenate] was associated with a 1.50-fold increased risk of skin lesions (multivariate odds ratio = 1.50; 95% confidence interval, 1.00-2.26). We observed significant interaction on the multiplicative scale between GSTT1 wildtype and secondary methylation ratio [dimethylarsinic acid/MMA; likelihood ratio test (LRT), p = 0.01]. No significant interactions were observed for GSTM1 or GSTP1 or for primary methylation ratios. CONCLUSION: Our findings suggest that increasing primary methylation ratios are associated with an increase in risk of arsenic-related skin lesions. The interaction between GSTT1 wildtype and secondary methylation ratio modifies risk of skin lesions among arsenic-exposed individuals.

BackgroundAs the next generation of scientists enters the field of environmental health, it is imperative that they view their contributions in the context of global environmental stewardship. In this commentary, a group of international graduate students facilitated by three experienced environmental health scientists present their views on what they consider to be the global environmental health concerns of today. This group convened initially in October 2004 at an international health conference in Prague, Czech Republic.ObjectivesIn this report we identify perceived environmental health concerns that exist around the world, with a focus on Central and Eastern Europe. Additionally, we address these perceived problems and offers some potential solutions.DiscussionAt the meeting, students were invited to participate in two panel discussions. One group of young international scientists identified several significant global environmental health concerns, including air pollution, occupational hazards, and risk factors that may exacerbate current environmental health issues. The second panel determined that communication, education, and regulation were the mechanisms for addressing current environmental challenges.ConclusionsIn this commentary we expand on the views presented at the meeting and represent the concerns of young investigators from nine different countries. We provide ideas about and support the exchange of information between developed and developing countries on how to handle the environmental health challenges that face the world today.

An established exposure-response relationship exists between water arsenic levels and skin lesions. Results of previous studies with limited historical exposure data, and laboratory animal studies suggest that diet may modify arsenic metabolism and toxicity. In this study, we evaluated the effect of diet on the risk of arsenic-related skin lesions in Pabna, Bangladesh. Six hundred cases and 600 controls loosely matched on age and sex were enrolled at Dhaka Community Hospital, Bangladesh, in 2001-2002. Diet, demographic data, and water samples were collected. Water samples were analyzed for arsenic using inductively coupled plasma mass spectroscopy. Betel nut use was associated with a greater risk of skin lesions in a multivariate model [odds ratio (OR)= 1.67; 95% confidence interval (CI), 1.18-2.36]. Modest decreases in risk of skin lesions were associated with fruit intake 1-3 times/month (OR = 0.68; 95%CI, 0.51-0.89) and canned goods at least 1 time/month (OR = 0.41; 95% CI, 0.20-0.86). Bean intake at least 1 time/day (OR = 1.89; 95% CI, 1.11-3.22) was associated with increased odds of skin lesions. Betel nut use appears to be associated with increased risk of developing skin lesions in Bangladesh. Increased intake of fruit and canned goods may be associated with reduced risk of lesions. Increased intake of beans may be associated with an increased risk of skin lesions. The results of this study do not provide clear support for a protective effect of vegetable and overall protein consumption against the development of skin lesions, but a modest benefit cannot be excluded. Key words: arsenic, Bangladesh, betel nut, case-control, diet.

Recent in vitro studies have suggested a potential role for antimony as a confounder in human health studies related to arsenic in drinking water. We measured tube-well water concentrations of antimony and arsenic in the Pabna region of Bangladesh, where arsenic concentrations are known to be elevated and the concentrations of antimony have not yet been thoroughly documented. Two hundred forty-five tube-well water samples were collected from various regions in Pabna, Bangladesh, as part of an ongoing case-control study. Water samples were analyzed for arsenic and antimony concentrations by inductively coupled plasma-mass spectrometry using U.S. Environmental Protection Agency method 200.8. The arsenic concentrations in the tube-well water samples ranged from < 1 micro g/L to 747 micro g/L. All 245 water samples had antimony concentrations < 1 micro g/L. Based on consideration of the concentrations used the in vitro studies compared with field-observed concentrations, our results do not support the hypothesis that antimony would be a significant confounder in observed relationships between arsenic exposure through drinking water and potential health outcomes in Pabna, Bangladesh. Key words: antimony, arsenic, Bangladesh, drinking water, tube well.

Malignant melanoma, a type of cancer that accounts for 1% to 3% of all malignant neoplasms in 20 times more frequent in the American white than black population. During a computer-aided retrospective chart review of more than 2,500 patients with melanoma being followed up at the Duke University Comprehensive Cancer Center, 31 blacks have been identified. Primary lesions of the foot were predominant in blacks with melanoma, and a high percentage of these were classified pathologically as acral lentiginous primary lesions. Black patients had a more advanced stage of disease at first presentation and a more deeply invasive primary lesion than their white counterparts. Five-year survival for the total black population was 23%. Blacks had a significantly worse prognosis than the white population when a comparison with the total group was made that was controlled for sex, age, site of primary lesion, stage of disease at presentation, and Clark level of primary melanoma lesion. This emphasizes the aggressive nature of this disease in the American black.