Faculty Bibliography

In humans, taurine (2-aminoethanesulfonic acid) is mainly obtained from diet. Despite the fact that the health effects of taurine are largely unknown, taurine has become a popular supplement and ingredient in energy drinks in recent years. Evidence from mechanistic and animal studies has shown that the main biological actions of taurine include its ability to conjugate bile acids, regulate blood pressure (BP), and act as a potent antioxidant and anti-inflammatory agent. These actions suggest that high levels of taurine may be protective against coronary heart disease (CHD). However, data from epidemiologic and intervention studies in humans are limited. We review what is known about taurine\'s metabolism, its transportation in the body, its food sources, and evidence of its effect on cardiovascular health from in vitro, animal, and epidemiologic studies. We also discuss shortcomings of the human studies that need to be addressed in the future. The identification of taurine as a preventive factor for CHD may be of great public health importance

OBJECTIVES: We examined associations between immigration and acculturation attributes and oral disease among immigrants. METHODS: We conducted a large cross-sectional study of 1318 immigrants in New York City. We performed comprehensive interviews and oral examinations of the participants and used linear regression models to assess differences in oral disease levels among immigrant subgroups. We also constructed proportional odds models to evaluate the association of oral disease level with length of stay in the United States, age at immigration, and language preference. RESULTS: After we controlled for most known risk factors, country of birth and age at immigration were associated with variations in oral disease prevalence and need for oral health care. Length of stay was inversely associated with need for treatment of dental caries but not with any other indicator of oral disease. Language preference was not associated with any indicator of oral disease. CONCLUSIONS: Immigrants' country of birth, length of stay in the United States, and age at immigration played important roles in their oral disease prevalence, independently of most known risk factors for oral diseases. Our findings emphasize the need for more studies to elucidate the complex relationships of ethnicity, socioeconomic status, and culturally influenced factors that impact immigrants' oral health.

The contamination of groundwater by arsenic in Bangladesh is a major public health concern affecting 35-75 million people. Although it is evident that high levels (>300 mug/L) of arsenic exposure from drinking water are related to adverse health outcomes, health effects of arsenic exposure at low-to-moderate levels (10-300 mug/L) are not well understood. We established the Health Effects of Arsenic Longitudinal Study (HEALS) with more than 20,000 men and women in Araihazar, Bangladesh, to prospectively investigate the health effects of arsenic predominately at low-to-moderate levels (0.1 to 864 mug/L, mean 99 mug/L) of arsenic exposure. Findings to date suggest adverse effects of low-to-moderate levels of arsenic exposure on the risk of pre-malignant skin lesions, high blood pressure, neurological dysfunctions, and all-cause and chronic disease mortality. In addition, the data also indicate that the risk of skin lesion due to arsenic exposure is modifiable by nutritional factors, such as folate and selenium status, lifestyle factors, including cigarette smoking and body mass index, and genetic polymorphisms in genes related to arsenic metabolism. The analyses of biomarkers for respiratory and cardiovascular functions support that there may be adverse effects of arsenic on these outcomes and call for confirmation in large studies. A unique strength of the HEALS is the availability of outcome data collected prospectively and data on detailed individual-level arsenic exposure estimated using water, blood and repeated urine samples. Future prospective analyses of clinical endpoints and related host susceptibility will enhance our knowledge on the health effects of low-to-moderate levels of arsenic exposure, elucidate disease mechanisms, and give directions for prevention

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