Faculty Bibliography

Chronic arsenic exposure is a world wide health problem. Although arsenic induced cancer has been widely studied, comparatively little attention has been paid to arsenic induced vascular disease. Epidemiological studies have shown that chronic arsenic exposure is associated with increased morbidity and mortality from cardiovascular disease. In addition, studies suggest that susceptibility to arsenic induced vascular disease may be modified by nutritional factors in addition to genetic factors. Recently, animal models for arsenic induced atherosclerosis and liver sinusoidal endothelial cell dysfunction have been developed. Initial studies in these models show that arsenic exposure accelerates and exacerbates atherosclerosis in ApoE-knockout mice. Microarray studies of liver mRNA and micoRNA abundance in mice exposed in utero suggest that a permanent state of stress is induced by the arsenic exposure. Furthermore, the livers of the arsenic exposed mice have activated pathways involved in immune responses suggesting a pro-hyperinflammatory state. Arsenic exposure of mice after weaning show a clear dose response in the extent of disease exacerbation. In addition, increased inflammation in arterial wall is evident. In response to arsenic stimulated oxidative signaling, liver sinusoidal endothelium differentiates into a continuous endothelium that limits nutrient exchange and waste elimination. Data suggest that NADPH oxidase derived superoxide or its derivatives are essential second messengers in the signaling pathway for arsenic-stimulated vessel remodeling. The recent findings provide future directions for research into the cardiovascular effects of arsenic exposure

BACKGROUND: In Bangladesh, millions of people are exposed to arsenic in drinking water; arsenic is associated with increased risk of cancer. Once ingested, arsenic is metabolized via methylation and excreted in urine. Knowledge about nutritional factors affecting individual variation in methylation is limited. OBJECTIVES: The purpose of this study was to examine associations between intakes of protein, methionine, and cysteine total urinary arsenic in a large population-based sample. METHODS: The study subjects were 10,402 disease-free residents of Araihazar, Bangladesh, who participated in the Health Effects of Arsenic Longitudinal Study (HEALS). Food intakes were assessed using a validated food frequency questionnaire developed for the study population. Nutrient composition was determined by using the U.S. Department of Agriculture National Nutrient Database for Standard Reference. Generalized estimating equations were used to examine association between total urinary arsenic across quintiles of nutrient intakes while controlling for arsenic exposure from drinking water and other predictors of urinary arsenic. RESULTS: Greater intakes of protein, methionine, and cysteine were associated with 10-15% greater total urinary arsenic excretion, after controlling for total energy intake, body weight, sex, age, tobacco use, and intake of some other nutrients. CONCLUSIONS: Given previously reported risks between lower rates of arsenic excretion and increased rates of cancer, these findings support the role of nutrition in preventing arsenic-related disease

The protective effect of full-term pregnancy against breast cancer is thought to be induced by two placental hormones: human chorionic gonadotropin and human chorionic somatotropin hormone (CSH) produced by the placental trophoblastic cells. We hypothesized that variants in placental genes encoding these hormones may alter maternal breast cancer risk subsequent to pregnancy. We conducted a case-control study to examine the association between polymorphisms in a woman's placental (i.e., her offspring's) homologous chorionic gonadotrophin beta5 (CGB5) and CSH1 genes and her post-pregnancy breast cancer risk. A total of 293 breast cancer cases and 240 controls with at least one offspring with available DNA were selected from the New York site of the Breast Cancer Family Registry. Three single nucleotide polymorphisms (SNP) in CGB5 and CSH1 genes were genotyped for 844 offspring of the cases and controls. Overall, maternal breast cancer risk did not significantly differ by the offspring's carrier status of the three SNPs. Among women with an earlier age at childbirth (younger than the median age of 26 years), those with a child carrying the variant C allele of CGB5 rs726002 SNP had an elevated breast cancer risk [odds ratio (OR), 2.09; 95% confidence interval (95% CI), 1.17-3.73]. Among women with a later age at childbirth, breast cancer risk did not differ by offspring's carrier status of CGB5 rs726002 SNP (OR, 0.90; 95% CI, 0.53-1.51; P for interaction = 0.04). The findings suggest that placental CGB5 genotype may be predictive of maternal post-pregnancy breast cancer risk among women who give birth early in life. [Cancer Res 2008;68(23):9729-34]

Due to the established association between estrogen levels and breast cancer risk, polymorphic variation in genes regulating estrogen levels is thought to be related to breast cancer risk. Aromatase, the protein product of the CYP19 gene, is involved in the production of endogenous estrogens via androgen conversion. We examined whether polymorphic variation in CYP19 associated with increased breast cancer risk in a population based case-control study. We examined two single nucleotide polymorphisms (SNP), rs1008805 (A/G) and rs730154 (C/T), which have been shown to tag SNPs within two different haplotype blocks in CYP19. Among premenopausal women, the presence of at least one G allele at rs1008805 was significantly associated with an increase in the risk of breast cancer (OR = 1.72 [95% CI, 1.20-2.49]), especially with estrogen and progesterone receptor negative breast cancer (OR = 3.89 [1.74-8.70] and OR = 2.52 [1.26-5.05], respectively). No association was observed among postmenopausal women (OR = 1.06 [0.82-1.36]). There was no significant association between rs730154 and breast cancer, regardless of menopausal status. Our results suggest that premenopausal women carrying the G allele at CYP19 rs1008805 have increased risk of breast cancer. The finding supports the potential role of variation in estrogen biosynthesis genes in premenopausal breast cancer risk

Background. @nbsp; Asthma, a serious health problem worldwide, is becoming more common. Colonization with Helicobacter pylori, a major human indigenous (commensal) microbe, during early life may be relevant to the risk of childhood asthma. Methods. @nbsp; We conducted cross-sectional analyses, using data from 7412 participants in the National Health and Nutrition Examination Survey (NHANES) 1999-2000, to assess the association between H. pylori and childhood asthma. Results. @nbsp; H. pylori seropositivity was inversely associated with onset of asthma before 5 years of age and current asthma in children aged 3-13 years. Among participants 3-19 years of age, the presence of H. pylori was inversely related to ever having had asthma (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.45-1.06), and the inverse association with onset of asthma before 5 years of age was stronger (OR, 0.58; 95% CI, 0.38-0.88). Among participants 3-13 years of age, H. pylori positivity was significantly inversely associated with current asthma (OR, 0.41; 95% CI, 0.24-0.69). H. pylori seropositivity also was inversely related to recent wheezing, allergic rhinitis, and dermatitis, eczema, or rash. Conclusions. @nbsp; This study is the first to report an inverse association between H. pylori seropositivity and asthma in children. The findings indicate new directions for research and asthma prevention

BACKGROUND: An estimated 25-40 million of the 127 million people of Bangladesh have been exposed to high levels of naturally occurring arsenic from drinking groundwater. The mitigating effects of diet on arsenic-related premalignant skin lesions are largely unknown. OBJECTIVES: The purpose of this study was to clarify the effects of the vitamin B group (thiamin, riboflavin, niacin, pyridoxine, and cobalamin) and antioxidants (vitamins A, C, and E) on arsenic-related skin lesions. METHODS: We performed a cross-sectional study using baseline data from the Health Effects of Arsenic Longitudinal Study (HEALS), 2000-2002, with individual-level, time-weighted measures of arsenic exposure from drinking water. A total of 14,828 individuals meeting a set of eligibility criteria were identified among 65,876 users of all 5,996 tube wells in the 25-km(2) area of Araihazar, Bangladesh; 11,746 were recruited into the study. This analysis is based on 10,628 subjects (90.5%) with nonmissing dietary data. Skin lesions were identified according to a structured clinical protocol during screening and confirmed with further clinical review. RESULTS: Riboflavin, pyridoxine, folic acid, and vitamins A, C, and E significantly modified risk of arsenic-related skin lesions. The deleterious effect of ingested arsenic, at a given exposure level, was significantly reduced (ranging from 46% reduction for pyridoxine to 68% for vitamin C) for persons in the highest quintiles of vitamin intake. CONCLUSIONS: Intakes of B-vitamins and antioxidants, at doses greater than the current recommended daily amounts for the country, may reduce the risk of arsenic-related skin lesions in Bangladesh