Genetic variants associated with arsenic susceptibility: study of purine nucleoside phosphorylase, arsenic (+3) methyltransferase, and glutathione S-transferase omega genes

BACKGROUND: Individual variability in arsenic metabolism may underlie individual susceptibility toward arsenic-induced skin lesions and skin cancer. Metabolism of arsenic proceeds through sequential reduction and oxidative methylation being mediated by the following genes: purine nucleoside phosphorylase (PNP), arsenic (+3) methyltransferase (As3MT), glutathione S-transferase omega 1 (GSTO1), and omega 2 (GSTO2). PNP functions as arsenate reductase; As3MT methylates inorganic arsenic and its metabolites; and both GSTO1 and GSTO2 reduce the metabolites. Alteration in functions of these gene products may lead to arsenic-specific disease manifestations. OBJECTIVES: To find any probable association between arsenicism and the exonic single nucleotide polymorphisms (SNPs) of the above-mentioned arsenic-metabolizing genes, we screened all the exons in those genes in an arsenic-exposed population. METHODS: Using polymerase chain reaction restriction fragment length polymorphism analysis, we screened the exons in 25 cases (individuals with arsenic-induced skin lesions) and 25 controls (individuals without arsenic-induced skin lesions), both groups drinking similar arsenic-contaminated water. The exonic SNPs identified were further genotyped in a total of 428 genetically unrelated individuals (229 cases and 199 controls) for association study. RESULTS: Among four candidate genes, PNP, As3MT, GSTO1, and GSTO2, we found that distribution of three exonic polymorphisms, His20His, Gly51Ser, and Pro57Pro of PNP, was associated with arsenicism. Genotypes having the minor alleles were significantly overrepresented in the case group: odds ratio (OR) = 1.69 [95% confidence interval (CI), 1.08-2.66] for His20His; OR = 1.66 [95% CI, 1.04-2.64] for Gly51Ser; and OR = 1.67 [95% CI, 1.05-2.66] for Pro57Pro. CONCLUSIONS: The results indicate that the three PNP variants render individuals susceptible toward developing arsenic-induced skin lesions.     

Arsenic in drinking water and the prevalence of respiratory effects in West Bengal, India

BACKGROUND: A large population in West Bengal, India has been exposed to naturally occurring inorganic arsenic through their drinking water. A cross-sectional survey involving 7683 participants of all ages was conducted in an arsenic-affected region between April 1995 and March 1996. The main focus of the study was skin keratoses and pigmentation alterations, two characteristic signs of ingested inorganic arsenic. Strong exposure-response gradients were found for these skin lesions. The study also collected limited information concerning respiratory system signs and symptoms, which we report here because increasing evidence suggests that arsenic ingestion also causes pulmonary effects. METHODS: Participants were clinically examined and interviewed, and the arsenic content in their current primary drinking water source was measured. There were few smokers and analyses were confined to non-smokers (N = 6864 participants). RESULTS: Among both males and females, the prevalence of cough, shortness of breath, and chest sounds (crepitations and/or rhonchi) in the lungs rose with increasing arsenic concentrations in drinking water. These respiratory effects were most pronounced in individuals with high arsenic water concentrations who also had skin lesions. Prevalence odds ratio (POR) estimates were markedly increased for participants with arsenic-induced skin lesions who also had high levels of arsenic in their current drinking water source (> or = 500 microg/l) compared with individuals who had normal skin and were exposed to low levels of arsenic (<50 microg/l). In participants with skin lesions, the age-adjusted POR estimates for cough were 7.8 for females (95% CI : 3.1-19.5) and 5.0 for males (95% CI : 2.6-9.9); for chest sounds POR for females was 9.6 (95% CI : 4.0-22.9) and for males 6.9 (95% CI : 3.1-15.0). The POR for shortness of breath in females was 23.2 (95% CI : 5.8-92.8) and in males 3.7 (95% CI : 1.3-10.6). CONCLUSION: These results add to evidence that long-term ingestion of inorganic arsenic can cause respiratory effects.     

Nutritional factors and susceptibility to arsenic-caused skin lesions in West Bengal, India

There has been widespread speculation about whether nutritional deficiencies increase the susceptibility to arsenic health effects. This is the first study to investigate whether dietary micronutrient and macronutrient intake modulates the well-established human risk of arsenic-induced skin lesions, including alterations in skin pigmentation and keratoses. The study was conducted in West Bengal, India, which along with Bangladesh constitutes the largest population in the world exposed to arsenic from drinking water. In this case-control study design, cases were patients with arsenic-induced skin lesions and had < 500 microg/L arsenic in their drinking water. For each case, an age- and sex-matched control was selected from participants of a 1995-1996 cross-sectional survey, whose drinking water at that time also contained < 500 microg/L arsenic. Nutritional assessment was based on a 24-hr recall for major dietary constituents and a 1-week recall for less common constituents. Modest increases in risk were related to being in the lowest quintiles of intake of animal protein [odds ratio (OR) = 1.94; 95% confidence interval (CI), 1.05-3.59], calcium (OR = 1.89; 95% CI, 1.04-3.43), fiber (OR = 2.20; 95% CI, 1.15-4.21), and folate (OR = 1.67; 95% CI, 0.87-3.2). Conditional logistic regression suggested that the strongest associations were with low calcium, low animal protein, low folate, and low fiber intake. Nutrient intake was not related to arsenic exposure. We conclude that low intake of calcium, animal protein, folate, and fiber may increase susceptibility to arsenic-caused skin lesions. However, in light of the small magnitude of increased risks related to these dietary deficiencies, prevention should focus on reducing exposure to arsenic.     

Respiratory effects and arsenic contaminated well water in Bangladesh

Arsenic in drinking water causes a widespread concern in Bangladesh, where a major proportion of tube wells is contaminated. Arsenic ingestion causes skin lesions, which is considered as definite exposure. A prevalence comparison study of respiratory effects among subjects with and without arsenic exposure through drinking water was conducted in Bangladesh. Exposed participants were recruited through health awareness campaign programs. Unexposed participants were randomly selected, where tubewells were not contaminated with arsenic. A total of 169 individuals participated (44 exposed individuals exhibiting skin lesions; 125 unexposed individuals). The arsenic concentrations ranged from 136 to 1000 micro g l(-1). The information regarding respiratory system signs and symptoms were also collected and the analyses were confined to nonsmokers. The crude prevalence ratio for chronic bronchitis and chronic cough amounted to 2.1 (95% CI 0.7-6.1). The prevalence ratios for chronic bronchitis increased with increasing exposure, i.e., 1.0, 1.6, 2.7 and 2.6 using unexposed as the reference. The prevalence ratios for chronic cough were 1.0, 1.6, 2.7 and 2.6 for the exposure categories, using the same unexposed as the reference. The dose-response trend was the same (P < 0.1) for both conditions. These results add to evidence that long-term ingestion of arsenic exposure can cause respiratory effects.     

Decrements in lung function related to arsenic in drinking water in West Bengal, India

During 1998-2000, the authors investigated relations between lung function, respiratory symptoms, and arsenic in drinking water among 287 study participants, including 132 with arsenic-caused skin lesions, in West Bengal, India. The source population involved 7,683 participants who had been surveyed for arsenic-related skin lesions in 1995-1996. Respiratory symptoms were increased among men with arsenic-caused skin lesions (versus those without lesions), particularly "shortness of breath at night" (odds ratio (OR) = 2.8, 95% confidence interval (CI): 1.1, 7.6) and "morning cough" (OR = 2.8, 95% CI: 1.2, 6.6) in smokers and "shortness of breath ever" (OR = 3.8, 95% CI: 0.7, 20.6) in nonsmokers. Among men with skin lesions, the average adjusted forced expiratory volume in 1 second (FEV1) was reduced by 256.2 ml (95% CI: 113.9, 398.4; p < 0.001) and the average adjusted forced vital capacity (FVC) was reduced by 287.8 ml (95% CI: 134.9, 440.8; p < 0.001). In men, a 100-microg/liter increase in arsenic level was associated with a 45.0-ml decrease (95% CI: 6.2, 83.9) in FEV1 (p = 0.02) and a 41.4-ml decrease (95% CI: -0.7, 83.5) in FVC (p = 0.054). Women had lower risks than men of developing skin lesions and showed little evidence of respiratory effects. In this study, consumption of arsenic-contaminated water was associated with respiratory symptoms and reduced lung function in men, especially among those with arsenic-related skin lesions.     

5,10-亚甲基四氢叶酸还原酶基因C677T位点突变与地方性砷中毒皮肤病变发生关系的研究

目的　 5 ,10- 亚甲基四氢叶酸还原酶 (MTHFR)是叶酸代谢关键酶 ,旨在了解该酶基因C6 77T位点突变是否是地方性砷中毒皮肤病变发生的遗传易感因素。方法　选择 5 0名出现砷性皮肤病变居民作为皮肤病变组 ,以同地区饮水砷浓度相近的 35名正常人作为对照 ,进行MTHFR基因C6 77T位点多态性分析(PCR- RFLP法 )、血清叶酸测定 (微生物法 )和维生素B1 2 测定 (电化学发光法 )。结果　皮肤病变组MTHFR基因C6 77T位点TT基因型占 34. 0 % ,T等位基因频率为 5 6 . 0 %。皮肤病变组和对照组基因型构成和等位基因频率差异无显著性。两组血清叶酸、VitB1 2 水平差异均无显著性。以血清叶酸水平≥ 10. 5nmol L且CC基因型作为参照 ,其它组粗OR值和经Logistic回归分析控制性别、年龄、水砷浓度、吸烟后的校正OR值均大于 1,但 95 %CI包含 1。结论　MTHFR基因C6 77T位点多态性与地方性砷中毒皮肤病变的发生无明显关联。     

A prospective study of arsenic exposure from drinking water and incidence of skin lesions in Bangladesh

Elevated concentrations of arsenic in groundwater pose a public health threat to millions of people worldwide. The authors aimed to evaluate the association between arsenic exposure and skin lesion incidence among participants in the Health Effects of Arsenic Longitudinal Study (HEALS). The analyses used data on 10,182 adults free of skin lesions at baseline through the third biennial follow-up of the cohort (2000-2009). Discrete-time hazard regression models were used to estimate hazard ratios and 95% confidence intervals for incident skin lesions. Multivariate-adjusted hazard ratios for incident skin lesions comparing 10.1-50.0, 50.1-100.0, 100.1-200.0, and ≥200.1 μg/L with ≤10.0 μg/L of well water arsenic exposure were 1.17 (95% confidence interval (CI): 0.92, 1.49), 1.69 (95% CI: 1.33, 2.14), 1.97 (95% CI: 1.58, 2.46), and 2.98 (95% CI: 2.40, 3.71), respectively (P(trend) = 0.0001). Results were similar for the other measures of arsenic exposure, and the increased risks remained unchanged with changes in exposure in recent years. Dose-dependent associations were more pronounced in females, but the incidence of skin lesions was greater in males and older individuals. Chronic arsenic exposure from drinking water was associated with increased incidence of skin lesions, even at low levels of arsenic exposure (<100 μg/L).     

Association between nutritional status and arsenicosis due to chronic arsenic exposure in Bangladesh

The role of nutritional factors in arsenic metabolism and toxicity is not clear. Provision of certain low protein diets resulted in decreased excretion of DMA and increased tissue retention of arsenic in experimental studies. This paper reports a prevalence comparison study conducted in Bangladesh to assess the nutritional status among the chronic arsenic exposed and unexposed population. 138 exposed individuals diagnosed as arsenicosis patients were selected from three known arsenic endemic villages of Bangladesh and age, sex matched 144 unexposed subjects were randomly selected from three arsenic free villages. The mean arsenic concentration in drinking water for the exposed and unexposed population was 641.15 and 13.5 microg L(-1) respectively. Body Mass Index was found to be lower than 18.5, the cut off point for malnutrition, in 57 (41.31%) out of 138 exposed arsenicosis cases and 31 (21.53%) out of 144 unexposed individuals. The crude prevalence ratio (or risk) was 1.92 (95% CI = 1.33-2.78) for poor nutritional status among the arsenicosis cases compared to the unexposed population. The findings of this study add to the evidence that poor nutritional status may increase an individual's susceptibility to chronic arsenic toxicity, or alternatively that arsenicosis may contribute to poor nutritional status.     

The impact of diet and betel nut use on skin lesions associated with drinking-water arsenic in Pabna, Bangladesh

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.     

A pathway-based analysis of urinary arsenic metabolites and skin lesions

Inorganic arsenic is metabolized to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA). Limited evidence suggests that the ability to fully metabolize arsenic into DMA influences susceptibility to disease. To determine whether percentage of MMA was predictive of disease, the authors used data from a case-control study conducted in Bangladesh (2001-2003). Persons who were diagnosed with keratosis, melanosis, Bowen's disease, or squamous cell carcinoma were matched on age, sex, and village to persons without these conditions. This analysis was restricted to persons who had no missing data on covariates (859 cases, 868 controls). A path analysis was used to evaluate simultaneously the association between the percentage of all urinary arsenic metabolites and the odds of skin lesions using PROC CALIS in SAS, version 9.1 (SAS Institute, Inc., Cary, North Carolina) and Mplus, version 6.1 (Muthén & Muthén, Los Angeles, California). The odds of skin lesions were significantly associated with log(10) percentage of MMA (adjusted odds ratio (OR(adj)) = 1.56, 95% confidence interval (CI): 1.15, 2.12) but not log(10) percentage of inorganic arsenic (OR(adj) = 1.06, 95% CI: 0.75, 1.50) or log(10) percentage of DMA (OR(adj) = 1.07, 95% CI: 0.33, 3.46). This novel analysis confirmed that persons who excrete a higher proportion of MMA have a greater risk of skin lesions after data are adequately controlled for urinary arsenic metabolites, current arsenic exposure, and other risk factors.     

Modification of risk of arsenic-induced skin lesions by sunlight exposure, smoking, and occupational exposures in Bangladesh

BACKGROUND: The risk of skin lesions associated with arsenic exposure from drinking water in Bangladesh is considerably greater in men than in women. METHODS: Using baseline data from 11,062 cohort members in the Health Effects of Arsenic Longitudinal Study in Araihazar, Bangladesh, we performed a cross-sectional analysis to evaluate whether the association between arsenic exposure from drinking water and the risk of skin lesions is modified by tobacco smoking, excessive sunlight, the use of fertilizer, and the use of pesticides. A time-weighted well arsenic concentration was estimated for each participant by incorporating history of well use. Relative excess risk for interaction (RERI) and its 95% confidence intervals (CIs) were estimated using adjusted prevalence odds ratios. RESULTS: We observed a synergistic effect between the highest level of arsenic exposure (> 113 microg/L) and tobacco smoking on risk of skin lesions in men (RERI = 1.5 [95% CI = 0.3 to 2.7] overall and 1.7 [0.2 to 3.4] for the subpopulation with longer-term arsenic exposure). We also observed suggestive synergistic effects between higher levels (28.1-113.0 microg/L and 113.1-864.0 microg/L) of arsenic exposure and fertilizer use in men (RERI = 1.0 [-0.2 to 2.2] and 1.3 [-0.2 to 2.9] respectively). Furthermore, the risk of skin lesions associated with any given level of arsenic exposure was greater in men with excessive sun exposure. The patterns of effect estimates in women indicate similar-but-weaker interaction effects of arsenic exposure with tobacco smoking and fertilizer use. CONCLUSIONS: These findings help explain why the risk of arsenic-related skin lesions was much greater in men than in women in Bangladesh. Because most arsenic-induced skin cancers arise from these skin lesions, treatment and remediation plans should take into consideration these etiologic cofactors.     

Arsenic exposure from drinking water and risk of premalignant skin lesions in Bangladesh: baseline results from the Health Effects of Arsenic Longitudinal Study

Millions of persons around the world are exposed to low doses of arsenic through drinking water. However, estimates of health effects associated with low-dose arsenic exposure have been extrapolated from high-dose studies. In Bangladesh, many persons have been exposed to a wide range of doses of arsenic from drinking water over a significant period of time. The authors evaluated dose-response relations between arsenic exposure from drinking water and premalignant skin lesions by using baseline data on 11,746 participants recruited in 2000-2002 for the Health Effects of Arsenic Longitudinal Study in Araihazar, Bangladesh. Several measures of arsenic exposure were estimated for each participant based on well-water arsenic concentration and usage pattern of the wells and on urinary arsenic concentration. In different regression models, consistent dose-response effects were observed for all arsenic exposure measures. Compared with drinking water containing <8.1 microg/liter of arsenic, drinking water containing 8.1-40.0, 40.1-91.0, 91.1-175.0, and 175.1-864.0 microg/liter of arsenic was associated with adjusted prevalence odds ratios of skin lesions of 1.91 (95% confidence interval (CI): 1.26, 2.89), 3.03 (95% CI: 2.05, 4.50), 3.71 (95% CI: 2.53, 5.44), and 5.39 (95% CI: 3.69, 7.86), respectively. The effect seemed to be influenced by gender, age, and body mass index. These findings provide information that should be considered in future research and policy decisions.     

Arsenic in drinking water and skin lesions: dose-response data from West Bengal,India

BACKGROUND: Over 6 million people live in areas of West Bengal, India, where groundwater sources are contaminated with naturally occurring arsenic. The key objective of this nested case-control study was to characterize the dose-response relation between low arsenic concentrations in drinking water and arsenic-induced skin keratoses and hyperpigmentation. METHODS: We selected cases (persons with arsenic-induced skin lesions) and age- and sex-matched controls from participants in a 1995-1996 cross-sectional survey in West Bengal. We used a detailed assessment of arsenic exposure that covered at least 20 years. Participants were reexamined between 1998 and 2000. Consensus agreement by four physicians reviewing the skin lesion photographs confirmed the diagnosis in 87% of cases clinically diagnosed in the field. RESULTS: The average peak arsenic concentration in drinking water was 325 microg/liter for cases and 180 microg/liter for controls. The average latency for skin lesions was 23 years from first exposure. We found strong dose-response gradients with both peak and average arsenic water concentrations. CONCLUSIONS: The lowest peak arsenic ingested by a confirmed case was 115 microg/liter. Confirmation of case diagnosis and intensive longitudinal exposure assessment provide the basis for a detailed dose-response evaluation of arsenic-caused skin lesions.     

The prevalence of subjective symptoms after exposure to arsenic in drinking water in Inner Mongolia,China

BACKGROUND: In Inner Mongolia, China, more than 300,000 people are chronically exposed to arsenic via their drinking water. We have previously reported that the prevalence of arsenical dermatosis was as high as 40% in the Hetao Plain area. However, the association between exposure to arsenic in drinking water and adverse health effects has not been fully examined. The purpose of this study was to examine the association between exposure to arsenic and prevalence of subjective symptoms. METHODS: A cross-sectional study was carried out in 431 residents of an arsenic-affected village and 189 residents of an arsenic-free village in 1996. Health-related interviews and physical examinations were conducted. The odds ratio for each subjective symptom was estimated, comparing residents of arsenic-free and affected villages. RESULTS: An arsenic level of 50+ microg/L was found in 90.6% of wells in the arsenic-affected village. Adjusted odds ratios of subjective symptoms, including coughs (odds ratio [OR] = 12.8, 95% confidence interval [CI]: 6.4-25.6), stomachaches (OR = 5.8, 95% CI: 3.6-9.4), palpitations (OR = 3.6, 95% CI: 1.5-8.2), urination problems (OR = 14.7, 95% CI: 3.3-65.5) and spontaneous abortions (OR = 2.7, 95% CI: 0.8-8.4), were markedly higher amongst residents of the arsenic-affected village, including those without arsenic dermatosis. CONCLUSIONS: The present study shows a high prevalence of subjective symptoms amongst residents of an arsenic-affected village. Symptoms occurred in people with and without arsenic dermatosis. Our findings suggest that symptoms other than dermatosis should be considered when a clinical diagnosis of arsenic toxicosis is made.     

Absence from childcare for respiratory illness

BACKGROUND: This population-based study investigated prospectively collected absence for respiratory illness data in two types of formal childcare (centre day care and family day care) in Perth, Western Australia, and factors associated with such absence. METHODS: All centres (n = 11) and 95% of family day care caregivers (n = 130) selected at random from licensing lists agreed to participate. Demographic details were obtained from a parental questionnaire and absences were recorded prospectively. Characteristics of the child and family were described using univariate odds ratios (OR) with 95% confidence intervals (CI). Multivariable analysis including generalized estimating equations was used to investigate having at least one absence for respiratory illness, having two or more absences, and having six or more absences. RESULTS: No statistically significant difference between care types for having had at least one absence episode for respiratory illness (OR 1.37, 95% CI 0.92-2.04) was found. Children who attended care for more days per week (OR 1.40, 95% CI 1.26-1.56) and those in the study for more weeks (OR 1.03, 95% CI 1.01-1.05) were more likely to be absent for respiratory illness. Those children in care for a greater number of hours per day were less likely to be absent (OR 0.88, 95% CI 0.80-0.97). Family history of bronchitis was also associated with absence for respiratory illness (OR 1.86, 95% CI 1.32-2.63). CONCLUSIONS: Statistically significant factors which had an impact on absence for respiratory illness were primarily those relating to the time spent in childcare and to family history of bronchitis.     

Iatrogenic outbreak of M. chelonae skin abscesses.

We describe an outbreak of skin lesions due to Mycobacterium chelonae subsp. abscessus associated with injections of lidocaine (lignocaine) given by a ''bioenergetic'' (a practitioner of alternative medicine) in Colombia. The lidocaine carpules and the lesions of the patients yielded mycobacteria with identical biochemical characteristics. Using the methodology of Sartwell and a case control design we examined the incubation period and assessed risk factors. Of 667 potentially exposed individuals, a total of 298 patients were interviewed, of whom 232 had skin lesions. The median incubation period was 30.5 days (range 15-59 days). Male sex (OR 2.85, 95% CI 1.26-6.51), increasing age (OR 1.25, 95% CI 1.03-1.53), subcutaneous injection route (OR 3.72, 95% CI 1.09-12.7) and number of injections (OR 1.01, 95% CI 1.00-1.03) were risk factors for disease. To our knowledge, this is the largest reported outbreak of M. chelonae infection, the first in which the organism has been isolated from the putative vehicle of infection, and the first in which the incubation period could be determined.     

Levels of arsenic in drinking-water and cutaneous lesions in Inner Mongolia

The most common health effects from drinking-water containing dissolved arsenic are skin abnormalities and lesions that are typically diagnosed as keratosis and pigment disorder. It was previously reported that the prevalence of cutaneous lesions was about 44% in arsenic-affected villages. However, there has been little research on the relationship between levels of arsenic in drinking-water and cutaneous lesions in Inner Mongolia. One study examined the association between the prevalence of keratosis and levels of arsenic exposure and the relationship between pigment disorder and levels of arsenic exposure among villagers aged 18 years or older in the arsenic-affected village of Hetao Plain in Inner Mongolia, PR China. The study included 227 participants who were affected by cutaneous lesions and 221 participants who were not affected by cutaneous lesions diagnosed in 1996 and 1998. Well-water drunk by the participants was collected to analyze arsenic content. Adjusting for age, sex, and smoking, logistic regression was applied to calculate the risks that arsenic in drinking-water will lead to cutaneous lesions. The results from the logistic regression showed that, with the increase of arsenic concentration in water, the risk of pigment disorder also increased (odds ratio [OR]=5.25, 95% confidence interval [CI] 1.32-83.24 for 50-199 microg/L; OR=10.97, 95% CI 1.50-79.95 for 200-499 [microg/L; OR=10.00, 95% CI 1.39-71.77 for > or = 500 microg/L (p=0.000), but the association between risk of keratosis and levels of arsenic was not significant (p=0.346). The findings suggest that keratosis is an early feature of arsenic poisoning, and the development of pigment disorder depends on higher doses of arsenic intake rather than keratosis. Further studies are needed to confirm that cutaneous lesions and other adverse health effects occur at low levels of arsenic exposure.     

Cancer screening practices among cancer survivors

BACKGROUND: Cancer survivors are more vulnerable to future cancers than individuals without cancer. As such, it is important to understand whether survivors are engaging in cancer screenings. METHODS: The screening practices reported in response to the 2000 Health Interview Survey of 2151 individuals with cancer were examined and compared to those of 30,195 individuals without cancer. RESULTS: The proportion of cancer survivors obtaining screenings ranged from 21% to 77%. Compared to individuals without cancer, women with cancer were more likely to have had a mammogram (odds ratio [OR]=1.8, 95% CI=1.5-2.1), a clinical breast exam (OR=2.2, 95% CI=1.9-2.5), and/or a Papanicolaou test (OR=1.3, 95% CI=1.1-1.5) in the recommended timeframe. Similarly, men with cancer were more likely than men without cancer to have had a prostate-specific antigen test performed (OR=2.5, 95% CI=2.0-3.0). All cancer survivors were more likely than individuals without a cancer diagnosis to have had a total body skin exam (OR=4.0, 95% CI=3.5-4.6), a fecal occult blood test (OR=1.4, 95% CI=1.2-1.6), and/or a colorectal exam (OR=2.2, 95% CI=1.9-2.5). Similar results were obtained when individuals diagnosed with the cancer for which the screen was designed to detect were excluded. CONCLUSIONS: The results demonstrate that cancer survivors have higher screening rates than individuals without a cancer diagnosis. Despite this, the proportion of survivors obtaining screenings varies considerably by the type of screen. An understanding of the impact of cancer screening in cancer survivors, as well as the reasons for and against obtaining cancer screenings, is necessary.     

Skin and respiratory symptoms among workers with suspected work-related disease

Background Many workers are exposed to chemicals that can cause both respiratory and skin responses. Although there has been much work on respiratory and skin outcomes individually, there are few published studies examining lung and skin outcomes together. Aims To identify predictors of reporting concurrent skin and respiratory symptoms in a clinical population. Methods Patients with possible work-related skin or respiratory disease were recruited. An interviewer- administered questionnaire collected data on skin and respiratory symptoms, health history, smoking habits, workplace characteristics and occupational exposures. Predictors of concurrent skin and respiratory symptoms were identified using multiple logistic regression models adjusted for age, sex and atopy. Results In total, 204 subjects participated; 46% of the subjects were female and the mean age was 45.4 years (SD = 10.5). Most subjects (n = 167, 82%) had possible work-related skin disease, compared with 37 (18%) subjects with possible work-related respiratory disease. Subjects with a history of eczema (OR 3.68, 95% CI 1.7-7.8), those from larger workplaces (OR 2.82, 95% CI 1.8-7.4) and those reporting respirator use at work (OR 2.44, 95% CI 1.2-4.8) had significantly greater odds of reporting both work-related skin and respiratory symptoms. Current smoking was also associated with reporting concurrent skin and respiratory symptoms (OR 2.57, 95% CI 1.2-5.8). Conclusions Workers reported symptoms in both systems, and this may be under-recognised both in the workplace and the clinic. The association between history of eczema and concurrent skin and respiratory symptoms suggests a role for impaired barrier function but needs further investigation.     

胸苷酸合成酶基因多态和生活习惯及亚甲基四氢叶酸还原酶基因协同作用与胃癌的易感性

目的　研究胸苷酸合成酶 (TS) 3’ UTR基因多态和生活习惯及亚甲基还原酶基因相互作用与胃癌易感性的关系。方法　在上消化道癌高发区淮安市进行病例对照研究 (胃癌患者 1 0 7例 ,人群对照 2 0 0名 ) ,调查研究对象的生活习惯 ,采用聚合酶链反应 限制性片段长度多态性 (PCR RFLP)技术检测研究对象的TS 3’ UTR基因型。结果　 (1 )胃癌组中TS +6bp +6bp、+6bp - 6bp、- 6bp - 6bp基因型频度分别为5 .6 %、47.7%和 46 .7% ,与对照组的 9.0 %、54 .0 %和 37.0 %相比 ,差异无显著性 (χ2 =3 .1 90 ,P =0 .2 0 3)。与携带 +6bp等位基因者相比 ,携带TS - 6bp - 6bp基因型者胃癌发生的危险性有所升高 (调整OR =1 .36 ,95 %CI:1 .0 0～ 1 .78,P =0 .0 4 7)。 (2 )TS - 6bp - 6bp基因型对吸烟、饮酒及不饮茶的习惯在胃癌发生中的作用有放大效应。与携带 +6bp等位基因且不吸烟者或不经常饮酒者或饮茶者相比 ,携带 - 6bp - 6bp基因型且有吸烟习惯者或经常饮酒者或不饮茶者发生胃癌的调整OR分别为 2 .79(95 %CI :1 .51～ 5 .1 8)、1 .76(95 %CI:1 .0 7～ 2 .90 )和 2 .34(95 %CI :1 .43～ 3 .82 )。 (3)TS - 6bp - 6bp基因型与亚甲基四氢叶酸还原酶 (MTHFR)C T或T T基因型有协同作用。携带TS - 6bp - 6bp基因型同时