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.     

Comparison of health effects between individuals with and without skin lesions in the population exposed to arsenic through drinking water in West Bengal, India

A study was conducted to explore the effect of arsenic causing conjunctivitis, neuropathy and respiratory illness in individuals, with or without skin lesions, as a result of exposure through drinking water, contaminated with arsenic to similar extent. Exposed study population belongs to the districts of North 24 Parganas and Nadia, West Bengal, India. A total of 725 exposed (373 with skin lesions and 352 without skin lesions) and 389 unexposed individuals were recruited as study participants. Participants were clinically examined and interviewed. Arsenic content in drinking water, urine, nail and hair was estimated. Individuals with skin lesion showed significant retention of arsenic in nail and hair and lower amount of urinary arsenic compared to the group without any skin lesion. Individuals with skin lesion also showed higher risk for conjunctivitis ((odd's ratio) OR: 7.33, 95% CI: 5.05-10.59), peripheral neuropathy (OR: 3.95, 95% CI: 2.61-5.93) and respiratory illness (OR: 4.86, 95% CI: 3.16-7.48) compared to the group without any skin lesion. The trend test for OR of the three diseases in three groups was found to be statistically significant. Again, individuals without skin lesion in the exposed group showed higher risk for conjunctivitis (OR: 4.66, 95% CI: 2.45-8.85), neuropathy (OR: 3.99, 95% CI: 1.95-8.09), and respiratory illness (OR: 3.21, 95% CI: 1.65-6.26) when compared to arsenic unexposed individuals. Although individuals with skin lesions were more susceptible to arsenic-induced toxicity, individuals without skin lesions were also subclinically affected and are also susceptible to arsenic-induced toxicity and carcinogenicity when compared to individuals not exposed to arsenic.     

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.     

Case-control analysis of dietary folate and risk of bladder cancer

Dietary folate, a water-soluble B vitamin found in a variety of fruits and vegetables, is of particular interest as a chemopreventive agent due to its role in DNA methylation and DNA synthesis and repair. We hypothesized that individuals with low folate intake would be at an increased risk for bladder cancer. Using an ongoing case-control study we assessed dietary folate in 409 incident bladder cancer patients and 451 healthy control subjects. A food-frequency questionnaire was used to estimate naturally occurring food folate (microg/kcal/day), dietary folate equivalents (DFE) from food sources (microg DFE/kcal/day), and DFE from all sources (microg DFE/kcal/day). Unconditional logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Bladder cancer patients reported a statistically significant lower intake of folate than control subjects for food folate and DFE from food sources (P < 0.001) but not for DFE from all sources (P = 0.061). In the highest quartile of food folate intake there was a 54% reduced risk for bladder cancer (OR = 0.46; 95% CI = 0.29-0.73) after adjusting for age, gender, ethnicity, smoking, and total energy intake. Similarly, the highest quartile of intake was associated with a 59% reduced risk for DFE from food sources (OR = 0.41; 95% CI = 0.26-0.65) and a 35% reduced risk for DFE from all sources (OR = 0.65; 95% CI = 0.42-1.00). In the joint-effects analyses using never smokers with high folate intake as the reference group (OR = 1.0), heavy smokers with low food folate intake had a 2.31-fold (95% CI = 1.11-4.82) increased risk, whereas heavy smokers with high folate intake had a reduced OR of 1.31 (95% CI = 0.53-3.26). Although the ORs were not statistically significant, light smokers and high folate intake exhibited a protective effect (OR = 0.62; 95% CI = 0.20-1.94), whereas an increased risk was observed for light smoking and low folate intake (OR = 1.41; 95% CI = 0.57-3.45). These patterns were consistent for the joint effects of smoking and DFE from food sources and DFE from all sources. In summary, high intake of dietary folate was associated with an overall decrease in bladder cancer risk. These data may have important implications for cancer prevention; however, large, hypothesis-driven, population-based clinical trials will be required to confirm these findings.     

Tea as a Potential Chemopreventive Agent in PhIP Carcinogenesis: Effects of Green Tea and Black Tea on PhIP-DNA Adduct Formation in Female F-344 Rats

Disturbances in DNA methylation have been hypothesized as being involved in carcinogenesis. It has been proposed that dietary factors such as folate, alcohol, and methionine may be associated with colon cancer because of their involvement in DNA methylation processes. Data from a large retrospective population‐based case‐control study of incident colon cancer were used to evaluate whether intake of alcohol and other dietary factors involved in DNA methylation are associated with colon cancer. Dietary data were obtained using a detailed diet history questionnaire. We did not observe strong independent associations between folate, vitamin B6, vitamin B12, methionine, or alcohol and risk of colon cancer after adjusting for body size, physical activity, cigarette smoking patterns, energy intake, and dietary intake of fiber and calcium. However, when assessing the associations between colon cancer and a composite dietary profile based on alcohol intake, methionine, folate, vitamin B12, and vitamin B6 we observed a trend of increasing risk as one moved from a low‐ to a high‐risk group. This trend was modest and most marked in those diagnosed at a younger age [odds ratio (OR) for men = 1.3, 95% confidence interval (CI) = 0.9–1.9; OR for women = 1.6, 95% CI= 1.0–2.6]. We observed that associations with this high‐risk dietary profile were greater among those who took aspirin or nonsteroidal anti‐inflammatory drugs on a regular basis and were younger at the time of diagnosis (men OR = 1.7, 95% CI = 1.0–3.2; women OR = 2.2, 95% CI= 1.0–4.8) and for distal tumors (men OR = 1.4, 95% CI = 0.9–2.3; women OR = 2.0, 95% CI = 1.0–3.8). Findings from this study provide only limited support for previously reported associations between dietary factors involved in DNA methylation and risk of colon cancer.     

Does the interaction between maternal folate intake and the methylenetetrahydrofolate reductase polymorphisms affect the risk of cleft lip with or without cleft palate?

Periconceptional folic acid supplementation may reduce the risk of cleft lip with or without cleft palate (CL(P)). Polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene reduce availability of 5-methyltetrahydrofolate, the predominant circulating form of folate. To determine the effect of MTHFR C677T and MTHFR A1298C genotypes and haplotypes on CL(P) risk and the interaction with maternal periconceptional dietary folate and folic acid supplement intake, the authors conducted a case-control triad study in the Netherlands (1998-2000) among 179 CL(P) and 204 control families. Infant and parental MTHFR C677T and MTHFR A1298C genotypes and haplotypes were not associated with CL(P) risk in the case-control and transmission disequilibrium test analyses. Mothers carrying the MTHFR 677TT genotype and who either did not use folic acid supplements periconceptionally or had a low dietary folate intake, or both, had an increased risk of delivering a CL(P) child (odds ratio (OR) = 5.9, 95% confidence interval (CI): 1.1, 30.9; OR = 2.8, 95% CI: 0.7, 10.5; OR = 10.0, 95% CI: 1.3, 79.1, respectively). No supplement use, low dietary folate intake, and maternal MTHFR 1298CC genotype increased the risk of CL(P) offspring almost sevenfold (OR = 6.5, 95% CI: 1.4, 30.2). Thus, the detrimental effect of low periconceptional folate intake on the risk of giving birth to a CL(P) child was more pronounced in mothers with the MTHFR 677TT or MTHFR 1298CC genotype.     

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。     

Calcium intake and 28-year cardiovascular and coronary heart disease mortality in Dutch civil servants.

Data obtained from a general health examination in 1953-1954 of 2605 middle-aged Dutch civil servants were analysed to investigate the relation between dietary calcium and cardiovascular (CVD) and coronary heart disease (CHD) mortality. Calcium intake was assessed at baseline by a 1-week food frequency recall. Multivariate adjusted odds ratios (OR) were calculated using the highest quintile of calcium intake as the reference. No statistically significant associations were observed for low calcium intake in 15 and 28 years of follow-up in both men and women. For men, multivariate adjusted OR for the lowest quintile of calcium intake were 1.3 (95% confidence interval (CI): 0.8-1.9) and 0.9 (95% CI: 0.6-1.6) for 28-year CVD and CHD mortality, respectively. For women, corresponding OR were 1.1 (95% CI: 0.6-2.0) and 1.1 (95% CI: 0.5-2.5). Although an inverse association between calcium intake and CVD and CHD mortality, possibly mediated by blood pressure, might be hypothesized, no clear association was observed. Because dietary patterns in the 1950s were quite stable, and major calcium sources were addressed, misclassification of calcium intake may not be fully responsible for this finding.     

Dietary intakes of selected nutrients and food groups and risk of cervical cancer

We investigated the relationships between intakes of selected dietary nutrients and food groups and risk of cervical cancer in a hospital-based, case-control study including 239 cases diagnosed with squamous cell carcinoma of the cervix and 979 hospital patients with nonneoplastic diagnoses who completed a self-administered questionnaire between 1982 and 1998 at Roswell Park Cancer Institute. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by unconditional logistic regression adjusting for age, education, smoking status, use of oral contraceptives, barrier contraceptives and spermicides, family history of cervical cancer, year questionnaire completed, and energy intake. Significant reductions in risk of approximately 40-60% were observed for women in the highest vs. lowest tertiles of dietary fiber (OR=0.59, 95% CI=0.37-0.94), vitamin C (OR=0.52, 95% CI=0.33-0.80), vitamin E (OR=0.44, 95% CI=0.27-0.72), vitamin A (OR=0.47, 95% CI=0.30-0.73), alpha-carotene (OR=0.41, 95% CI=0.27-0.63), beta-carotene (OR=0.44, 95% CI=0.29-0.68), lutein (OR=0.51, 95% CI=0.33-0.79), folate (OR=0.55, 95% CI=0.34-0.88), and total fruit and vegetable intake (OR=0.52, 95% CI=0.34-0.77). Our findings suggest that a diet rich in plant-based nutrients may be important in reducing the risk of cervical cancer.     

Blood concentrations of methionine, selenium, beta-carotene, and other micronutrients in a case-control study of arsenic-induced skin lesions in West Bengal, India

Previous studies have suggested that susceptibility to arsenic toxicity could be influenced by micronutrients, in particular selenium, methionine, and beta-carotene. A case-control study was conducted in West Bengal, India, in a region known to have groundwater arsenic contamination, to determine whether differences in micronutrient status contribute to susceptibility to arsenic-induced skin lesions. Micronutrient status was assessed by blood levels of specific micronutrients and metabolic indicators. Blood was obtained from 180 cases with skin lesions and 192 controls. Blood assays measured micronutrients and carotenoids (folate, selenium, vitamin B12, vitamin B6, retinol, alpha-tocopherol, lutein/zeaxanthin, beta-carotene, lycopene, beta-cryptoxanthin) and metabolic indicators such as glucose, cholesterol, transthyretin, amino acids, and proteins potentially associated with methylation (cysteine, homocysteine, methionine, glutathione). The distributions of nutrient concentrations were similar in cases and controls. The median selenium concentrations in cases and controls were both 1.15 micromol/L, and there was little evidence of differences in other micronutrients. Odds ratios (ORs) for arsenic-induced skin lesions were estimated for each quartile of nutrient concentrations, using the quartile with the highest nutrient level as the referent group. There were no clear trends associated with deficiencies of any micronutrient or metabolic indicator. For decreasing quartiles of selenium, the OR estimates were 1.00, 0.67, 0.99, 0.80; P=0.81; for methionine, the OR estimates were 1.00, 0.83, 0.78, 0.72; P=0.29. For beta-carotene, the ORs were 1.00, 0.53, 0.51, 0.96, demonstrating no increased risk at the lower quartiles. The measured micronutrients and metabolic indicators investigated do not appear to modify the risk of developing arsenic-induced skin lesions. The lack of any trend of increasing risk with lower selenium, vitamin E, and beta-carotene concentrations has important implications for proposed therapeutic interventions. The emphasis of interventions should be on reducing arsenic exposure.     

Relationship between folate status and tumour progression in patients with hepatocellular carcinoma

Previous studies with folate/methyl-deficient rat models proposed the role of folate deficiency in hepatocarcinogenesis and tumour progression. We investigated the relationship between folate status and tumour progression in patients with hepatocellular carcinoma (HCC). Ninety HCC patients (age 62 (sd 10) years) recruited through the Department of Internal Medicine, Chi-Mei Hospital, participated in this cross-sectional study. According to the clinical criteria, 44 % showed marginal folate deficiency (serum folate 7-14 nmol/l; folate intake 278 (sd 212) microg/d), and 16 % were folate deficient ( < 7 nmol/l; 207 (sd 113) microg/d). Serum folate showed inverse correlations with three elements of tumour progression: tumour size (r - 0.29; P = 0.005), tumour multiplicity (r - 0.24; P = 0.018) and metastasis (r - 0.39; P = 0.0001). When HCC progression was categorised into stages I to IV, serum folate decreased as HCC stage progressed (stage I, 24.5 (sd 11.5); stage IV, 10.3 (sd 3.3) nmol/l; P = 0.032). After adjustment for age, sex, lifestyle and dietary factors, patients with low blood folate status (serum folate < 14 nmol/l) had increased risks for advanced tumour progression in large tumours (OR 7.1 (95 % CI 2.27, 21.9); P = 0.0007), tumour multiplicity (OR 3.2 (95 % CI 1.07, 3.51); P = 0.004) and metastasis (OR 4.5 (95 % CI 1.11, 18.4); P = 0.03) relative to those with normal folate status. Further controlling for liver injury, tumour proliferation and tumour stage, however, negated the effect of folate on advanced tumour progression. The data thus suggest that low blood folate status could be a risk factor for tumour progression, which is modulated by clinical lesions present in HCC patients. Future studies with larger sample sizes are warranted to explore the joint effects of low folate and hepatic lesions in human HCC malignancy.     

Serum 25-hydroxyvitamin D, dietary calcium intake, and distal colorectal adenoma risk

Vitamin D has recently emerged as a potentially protective agent against colorectal neoplasia. We assessed the associations between dietary vitamin D, plasma 25-hydroxyvitamin D [25(OH)D], dietary calcium, and colorectal adenomas in a large screening sigmoidoscopy-based case-control study in Southern California. Because conversion of serum 25(OH)D to serum 1,25-vitamin D is highly regulated by serum calcium, we also assessed modification of the 25(OH)D-adenoma association by calcium intake. Cases were 473 subjects with a primary adenoma, and controls were 507 subjects who had no adenomas at sigmoidoscopy and no history of adenomas. Compared with those in the lowest quartile of intake, those in the highest quartile of dietary vitamin D had an adjusted odds ratio (OR) of 0.83 [95% confidence interval (CI) = 0.49-1.41] and those in the highest quartile of dietary calcium had an OR of 0.82 (95% CI = 0.49-1.25). There was a suggestion that plasma 25(OH)D may be protective in this population (OR for highest vs. lowest quartile = 0.74, 95% CI = 0.51-1.09). A significant protective effect of 25(OH)D was clearly evident only in those with calcium intakes below (OR = 0.40 for highest vs. lowest quartile, 95% CI = 0.22-0.71, p for trend = 0.005) and above (OR = 1.17, 95% CI = 0.69-1.99, p for trend = 0.94) the median calcium intake.     

Raw and cooked vegetables, fruits, selected micronutrients, and breast cancer risk: a case-control study in Germany

In 1998-2000, a case-control study of breast cancer was conducted in Heidelberg, Germany. Three hundred ten consecutively recruited cases with primary breast cancer were matched according to 10-yr age groups to 353 controls with conditions unrelated to diet or endocrine disorders. Intake of raw vegetables, total vegetables, and whole-grain products was inversely associated with breast cancer risk (highest vs. lowest quartile adjusted odds ratio [OR] 0.51, 95% confidence interval [CI] 0.31-0.84; OR = 0.62, 95% CI = 0.38-1.02; and OR = 0.57; 95% CI = 0.34-0.95, respectively). Also, high intake of some selected vitamins and minerals possessing putative DNA-stabilizing properties displayed significant inverse risk associations. Adjusted ORs were as follows: vitamin C (OR = 0.49, 95% CI = 0.2-0.88), folate equivalents (OR = 0.47, 95% CI = 0.25-0.88), b-carotene (OR = 0.46, 95% CI = 0.27-0.80), zinc (OR = 0.35, 95% CI = 0.15-0.78), and copper (OR = 0.51, 95% CI = 0.31-1.03). In contrast, no significant association with risk was seen for an increased intake of fruits, cooked vegetables, fiber, calcium, manganese, or iron. In this population of German women, components of raw vegetables and some micronutrients appear to decrease breast cancer risk.     

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.     

Nutrient intake and risk of squamous cell carcinoma of the esophagus: a case-control study in Uruguay

In 1996-2004 a case-control study on nutrient intake, dietary constituents and risk of squamous cell carcinoma of the esophagus was conducted in Montevideo, Uruguay. In fact, Uruguay, and especially its northern provinces, which border Brazil, are high-risk areas. The study included 234 cases and 936 controls. The controls were hospitalized patients with non-neoplastic disease, which was not related to tobacco smoking and alcohol drinking, and without recent changes in their diets. Controls were frequency matched to cases on age (10-yr intervals), sex, and residence (Montevideo and other provinces). Dietary constituents were energy adjusted using the residuals method and then categorized in quartiles according to the distribution of the controls. The final model included linoleic acid, lycopene, alpha-carotene, beta-cryptoxanthin, vitamin A, monounsaturated fat, total carbohydrates, beta-carotene, and folate. The odds ratio (OR) for high intake of linoleic acid was 1.4 (95% confidence interval, CI = 1.2-1.6), whereas lycopene displayed a strong protective effect (OR = 0.7; 95% CI = 0.6-0.9). The possible role of these and other dietary constituents in esophageal carcinogenesis is discussed.     

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.     

The association of calcium and vitamin D with risk of colorectal adenomas

The Polyp Prevention Trial (PPT) was a multicenter randomized clinical trial designed to determine the effects of a high-fiber, high-fruit and vegetable, low-fat diet on the recurrence of adenomatous polyps in the large bowel. Detailed dietary intake and supplement use data were collected at baseline and at each of 4 annual study visits. Adenoma recurrence was ascertained by complete colonoscopy at baseline and after 1 and 4 y. Recurrence was found in 754 of the 1905 trial participants. We evaluated the association between calcium and vitamin D intake and adenomatous polyp recurrence after adjusting for intervention group, age, gender, nonsteroidal anti-inflammatory drug use, total energy intake, and the interaction of gender and intervention group. Vitamin D models were also adjusted for the location of the clinic site. Dietary variables were adjusted for total energy intake via the residual method. There were no overall significant associations between adenoma recurrence and dietary calcium intake [odds ratio (OR) for the 5th compared with the lowest quintile = 0.91; 95% CI = 0.67-1.23; P-trend = 0.68], total calcium intake (OR = 0.86; 95% CI = 0.62-1.18; P-trend = 0.20), or dietary vitamin D intake (OR = 0.93; 95% CI = 0.69-1.25; P-trend = 0.43) averaged over follow-up. Total vitamin D intake was weakly inversely associated with adenoma recurrence (OR = 0.84; 95% CI = 0.62-1.13; P-trend = 0.03). Supplemental calcium and vitamin D use during follow-up also were inversely associated with adenoma recurrence (OR for any compared with no use = 0.82; 95% CI = 0.68-0.99; and OR = 0.82; 95% CI = 0.68-0.99; for calcium and vitamin D, respectively). Slightly stronger associations were noted for the prevention of multiple recurrences. Our analyses did not suggest a significant effect modification between total calcium and total vitamin D intake (P = 0.14) on risk for adenoma recurrence. This trial cohort provides some evidence that calcium and vitamin D may be inversely associated with adenoma recurrence.     

Dietary folate and depressive symptoms are associated in middle-aged Finnish men

Several cross-sectional studies have focused on the low blood folate levels of depressed patients. However, no published studies have examined the association between dietary folate and current symptoms of depression in a general population. We investigated the association between dietary folate, cobalamin, pyridoxine and riboflavin and current symptoms of depression in a cross-sectional general population study. We recruited 2682 men aged between 42 and 60 y from eastern Finland. Those who had a previous history of psychiatric disorder were excluded (n = 146, 5.6% of the cohort). Depressive symptoms were assessed with the 18-item Human Population Laboratory Depression Scale. Those who scored 5 or more at baseline were considered to have elevated depressive symptoms (n = 228, 9.3% of the cohort). The participants were grouped into thirds according to their dietary folate intake. Those in the lowest third of energy-adjusted folate intake had a higher risk of being depressed [odds ratio (OR) 1.67, 95% CI = 1.19-2.35, P = 0.003] than those in the highest folate intake third. This increased risk remained significant after adjustment for smoking habits, alcohol consumption, appetite, BMI, marital status, education, adulthood socioeconomic status and total fat consumption (OR = 1.46, 95% CI = 1.01-2.12, P = 0.044). There were no associations between the intake of cobalamin, pyridoxine or riboflavin, and depression. These results indicate that nutrition may have a role in the prevention of depression.     

Effect of nutrient intake and Helicobacter pylori infection on gastric cancer in Korea: a case-control study

To examine the effects of dietary factor and Helicobacter pylori (H. pylori) infection with emphasis on vitamin intake on the risk of gastric cancer (GC), we conducted a case-control study in South Korea, a high-risk area for GC. Trained dietitians interviewed 136 cases histologically diagnosed with GC. An equal number of hospital controls was selected by matching sex and age. High dietary intakes of vegetable fat [odds ratio (OR) = 0.35; 95% confidence interval (CI) = 0.15-0.83], folate (OR = 0.35; 95% CI = 0.13-0.96), and antioxidants, such as vitamin A (OR = 0.34; 95% CI = 0.13-0.83), beta-carotene (OR = 0.33; 95% CI = 0.13-0.82), vitamin C (OR = 0.26; 95% CI = 0.09-0.72), and vitamin E (OR = 0.41; 95% CI = 0.17-1.01), were shown to have a protective effect on GC risk using a multivariate model adjusting for foods significantly related to GC in our previous study (charcoal grilled beef, spinach, garlic, mushroom, and a number of types of kimchi) and supplement use. When stratified according to H. pylori infection, high intakes of vitamin C (OR = 0.10; 95% CI = 0.02-0.63) and vitamin E (OR = 0.16; 95% CI = 0.03-0.83) exhibited highly significant inverse associations with GC among the H. pylori-infected subjects compared with noninfected individuals. GC risk was significantly decreased only when consumption levels for two of these vitamins were high. Our findings suggest that high intake of antioxidant vitamins contribute to the reduction of GC risk and that GC risk in Korea may be decreased by encouraging those with H. pylori infection to increase their intake of antioxidant vitamins.     

Polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene, intakes of folate and related B vitamins and colorectal cancer: a case-control study in a population with relatively low folate intake

Folate is key in one-carbon metabolism, disruption of which can interfere with DNA synthesis, repair, and methylation. Efficient one-carbon metabolism requires other B vitamins and the optimal activity of enzymes including 5,10-methylenetetrahydrofolate reductase (MTHFR). We report a population-based case-control study of folate intake, related dietary factors and MTHFR polymorphisms (C677T, A1298C) and colorectal cancer in a population with relatively high colorectal cancer incidence and relatively low folate intake. A total of 264 cases with histologically confirmed incident colorectal cancer and 408 controls participated. There was no clear trend in risk with reported intakes of total, or dietary, folate, riboflavin, vitamin B12 or vitamin B6, nor were there interactions between folate intake and the other B vitamins or alcohol. For C677T, risk decreased with increasing variant alleles (multivariate OR for CT v. CC = 0.77 (95 % CI 0.52, 1.16); OR for TT v. CC = 0.62 (95 % CI 0.31, 1.24)), which, although not statistically significant, was consistent with previous studies. For A1298C, compared with AA subjects, CC subjects had modest, non-significant, reduced risk (multivariate OR = 0.81 (95 % CI 0.45, 1.49)). There were significant interactions between total folate and C677T (P = 0.029) and A1298C (P = 0.025), and total vitamin B6 and both polymorphisms (C677T, P = 0.016; A1298C, P = 0.033), although the patterns observed differed from previous studies. Seen against the setting of low folate intake, the results suggest that the role of folate metabolism in colorectal cancer aetiology may be more complex than previously thought. Investigation of particular folate vitamers (for example, tetrahydrofolate, 5,10-methylenetetrahydrofolate) may help clarify carcinogenesis pathways.