Circulating carotenoids and risk of breast cancer: pooled analysis of eight prospective studies.

BACKGROUND: Carotenoids, micronutrients in fruits and vegetables, may reduce breast cancer risk. Most, but not all, past studies of circulating carotenoids and breast cancer have found an inverse association with at least one carotenoid, although the specific carotenoid has varied across studies. METHODS: We conducted a pooled analysis of eight cohort studies comprising more than 80% of the world's published prospective data on plasma or serum carotenoids and breast cancer, including 3055 case subjects and 3956 matched control subjects. To account for laboratory differences and examine population differences across studies, we recalibrated participant carotenoid levels to a common standard by reassaying 20 plasma or serum samples from each cohort together at the same laboratory. Using conditional logistic regression, adjusting for several breast cancer risk factors, we calculated relative risks (RRs) and 95% confidence intervals (CIs) using quintiles defined among the control subjects from all studies. All P values are two-sided. RESULTS: Statistically significant inverse associations with breast cancer were observed for α-carotene (top vs bottom quintile RR = 0.87, 95% CI = 0.71 to 1.05, P(trend) = .04), ß-carotene (RR = 0.83, 95% CI = 0.70 to 0.98, P(trend) = .02), lutein+zeaxanthin (RR = 0.84, 95% CI = 0.70 to 1.01, P(trend) = .05), lycopene (RR = 0.78, 95% CI = 0.62 to 0.99, P(trend) = .02), and total carotenoids (RR = 0.81, 95% CI = 0.68 to 0.96, P(trend) = .01). ß-Cryptoxanthin was not statistically significantly associated with risk. Tests for heterogeneity across studies were not statistically significant. For several carotenoids, associations appeared stronger for estrogen receptor negative (ER(-)) than for ER(+) tumors (eg, ß-carotene: ER(-): top vs bottom quintile RR = 0.52, 95% CI = 0.36 to 0.77, P(trend) = .001; ER(+): RR = 0.83, 95% CI = 0.66 to 1.04, P(trend) = .06; P(heterogeneity) = .01). CONCLUSIONS: This comprehensive prospective analysis suggests women with higher circulating levels of α-carotene, ß-carotene, lutein+zeaxanthin, lycopene, and total carotenoids may be at reduced risk of breast cancer.

Subjects agree to participate in environmental health studies without fully comprehending the associated risk.

Recent advances in environmental health research have greatly improved our ability to measure and quantify how individuals are exposed. These advances, however, bring bioethical uncertainties and potential risks that individuals should be aware of before consenting to participate. This study assessed how well participants from two environmental health studies comprehended consent form material. After signing the consent form, participants were asked to complete a comprehension assessment tool. The tool measured whether participants could recognize or recall six elements of the consent form they had just reviewed. Additional data were collected to look for differences in comprehension by gender, age, race, and the time spent reading the original consent form. Seventy-three participants completed a comprehension assessment tool. Scores ranged from 1.91 to 6.00 (mean = 4.66); only three people had perfect comprehension scores. Among the least comprehended material were questions on study-related risks. Overall, 53% of participants were not aware of two or more study-related risks. As environmental public health studies pose uncertainties and potential risks, researchers need to do more to assess participants' understanding before assuming that individuals have given their 'informed' consent.

Strengthening public health ethics at the centers for disease control and prevention.

In early 2005, the Centers for Disease Control and Prevention (CDC) launched an initiative to strengthen leadership in public health ethics. This resulted in the formation of an external Ethics Subcommittee of the Advisory Committee to the Director, an internal CDC Public Health Ethics Committee, and the creation of a new position, the CDC Public Health Ethics Coordinator, to oversee the activities of these two committees and to serve as the main point of contact for public health ethics at the agency. Through this effort, the CDC is collaborating with the Ethics Subcommittee to develop ethical guidance documents that address specific public health program concerns, including pandemic influenza, emergency preparedness and response, and genomics. It is anticipated that as the public health ethics activities grow within the CDC, benefits will be seen in greater participation and partnership with affected stakeholders and strengthened public trust in health recommendations.

The night vision threshold test is a better predictor of low serum vitamin A concentration than self-reported night blindness in pregnant urban Nepalese women.

This study was conducted to validate the night vision threshold test (NVTT) as an indicator of night blindness. A total of 1401 pregnant women from the National Maternity Hospital participated in this study. Women were queried about night blindness and took the NVTT using standardized procedures after 10 min of dark adaptation. Sixteen percent failed the NVTT, but only 6.4% reported having night blindness. Blood samples from women who failed the NVTT (cases) and matched controls indicated the serum vitamin A (SVA) concentration was lower (P < 0.05) in cases (1.19 +/- 0.03 micromol/L) than in controls (1.29 +/- 0.03 micromol/L). The SVA concentrations did not differ between women who reported and did not report night blindness. The SVA concentration was correlated (r = 0.22, P < 0.001) with the NVTT scores. Twenty-five percent of women with an SVA < 0.35 micromol/L reported night blindness while 100% failed the NVTT. Nineteen percent of women with an SVA < 0.70 micromol/L reported night blindness while 73% failed the NVTT. A receiver operating characteristics analysis indicated that the NVTT had greater sensitivity (0.73 vs. 0.19) and less specificity (0.51 vs. 0.87) compared with reported night blindness for women with SVA < 0.70 micromol/L and greater sensitivity (100.0 vs. 0.73) and similar specificity (0.51 vs. 0.50) for women with SVA < 0.35 micromol/L. The NVTT identified women with low SVA and self-reported night blindness was misleading. We provide a preliminary algorithm to predict the population of women with low SVA concentrations.

Vitamin A levels and immunity in humans.

In animal studies, vitamin A deficiency induces a shift from type 2 (humoral) to type 1 (cellular) cytokines; there are no similar data for humans. Control of human immunodeficiency virus (HIV) and Mycobacterium tuberculosis infections requires type 1 cytokine (cellular) immunity. These infections and vitamin A deficiency are highly prevalent in Africa. We therefore examined the interactions among serum vitamin A levels, immune parameters, HIV infection status, Mycobacterium bovis BCG vaccine scarring (as an indicator of a type 1 cytokine profile), and clinical findings for 70 hospitalized children in Malawi, Africa. Directly conjugated monoclonal antibodies and flow cytometry were used to assess cell-specific cytokine production by peripheral blood monocytes and lymphocyte subpopulations. The statistical techniques employed included nonparametric statistics and logistic regression analyses. Thirty percent of the participants had severe vitamin A deficiency (<10 microg/dl), 34% had moderate deficiency (10 to <20 microg/dl), and 36% had normal levels (> or = 20 microg/dl). Vitamin A levels were lower for HIV-positive than for HIV-negative children (median, 10 and 17 microg/dl, respectively). Vitamin A-deficient children (<20 microg/dl) were more likely than non-vitamin A-deficient children to have higher proportions of natural killer (NK) cells (median, 8.3 and 5.2%, respectively) and lower ratios of interleukin-10-producing monocytes to tumor necrosis factor alpha-producing monocytes after induction (median, 1.0 and 2.3, respectively). Vitamin A-deficient children were also more likely than non-vitamin A-deficient children to exhibit respiratory symptoms (47% versus 12%) and visible BCG vaccine scars (83% versus 48%), which are indicative of a type 1 response to vaccination. Vitamin A status did not vary with gender, age, incidence of malaria parasitemia, blood culture positivity, or rates of mortality (6% of vitamin A-deficient children died versus 20% of non-vitamin A-deficient children). Lower vitamin A levels were associated with a relative type 1 cytokine dominance and proportionately more NK cells, both of which may be somewhat beneficial to persons who are exposed to HIV, M. tuberculosis, or other type 1 pathogens.