Background Low dietary folate intake is associated with several neoplasias, but reports are inconsistent for breast cancer. Additionally, the association of folate with breast cancer estrogen receptor (ER) status is not well established. Objective To determine if dietary intakes of folate, B-vitamins (B2, B6, B12) and methionine are associated with breast cancer risk and ER status in Hispanic, and non-Hispanic White women in the southwestern US. Materials and Methods Primary breast cancer cases (n = 2,325) in the 4-Corners region (Arizona, Colorado, New Mexico and Utah), diagnosed between October 1999 and May 2004, were identified through state cancer registries. Controls (n = 2,525) were frequency-matched by ethnicity and age (±5 years). Dietary intake, physical activity and other exposures were assessed using in-person interviews. Risk was assessed through multivariable and multinomial logistic regression with adjustment for relevant covariates. Result While there was no overall association with breast cancer, the highest quartile of folate intake was marginally inversely associated with ER− breast cancer (Odds Ratio (OR) = 0.50, 95%CI 0.25–1.00, p for trend = 0.07). Vitamin B12 intake was inversely associated with breast cancer also (OR = 0.73, 95%CI 0.53–1.00, p for trend = 0.06), particularly for the highest quartile of ER+ breast cancer (OR = 0.67, 95%CI 0.46–0.99, p for trend = 0.06), among NHW women (OR = 0.49, 95%CI 0.29–0.81, p for trend = 0.01) and invasive breast cancer (OR = 0.63; 95%CI: 0.42, 0.93, P trend = 0.01). Methionine intake was also inversely associated with ER+ breast cancer (OR for 4th quartile = 0.83, 95%CI 0.66–1.03, p for trend = 0.04), primarily among Hispanic women (OR = 0.71, 95%CI 0.47–1.06, and P for trend = 0.02). Conclusion Higher intake of folate is marginally associated with a lower risk for ER− breast cancer, and higher intakes of vitamin B-12 and methionine are marginally associated with a lower risk of ER+ breast cancer.

OBJECTIVE To determine whether the plasma level of sex hormone-binding globulin (SHBG) identifies South Asian Indian children at risk for metabolic syndrome. METHODS Adults and their children aged 5 to 9 years were recruited at the annual health fair at the Hindu temple serving the South Asian Indian community in Louisville, Kentucky. Anthropometric data were collected in adults and children, and blood pressure, lipid, and glucose levels were measured in adults. SHBG levels were measured in children using a fingerstick blood sample. In adults, metabolic syndrome was diagnosed according to the International Diabetes Federation criteria. Twelve months later, follow-up anthropometric data were obtained for a portion of the children. RESULTS The study included 30 sets of parents and 30 children. The prevalence of metabolic syndrome among 310 adults attending the health fair was 42% in men and 39% in women. Children with 1 parent with metabolic syndrome had 24% lower SHBG levels that increased to 55% if both parents had metabolic syndrome. SHBG levels were inversely related to waist circumference and to body mass index percentile. Both SHBG and waist circumference predicted weight gain over 1 year in children. CONCLUSIONS Low SHBG levels were found in South Asian Indian children whose parents had attributes of metabolic syndrome. The dose dependency of SHBG is consistent with inheritance of a genetic trait, and if the results are applicable to other racial/ethnic groups, SHBG may be a useful marker to identify at-risk children for early intervention.

Previous evidence suggests that the testicular negative feedback control of gonadotropin-releasing hormone-luteinizing hormone (LH) secretion may change as men age, and may thereby contribute to the hypogonadism that occurs as men grow older. To pursue this idea, we analyzed the results for 35 men with primary hypogonadism who were participants in an open-label multicenter study of testosterone replacement. LH, sex hormone-binding globulin (SHBG), and total and free testosterone and estradiol concentrations were measured in blood samples at baseline and after 2% testosterone gel was applied daily for 2 weeks. A 24-hour pharmacokinetic profile for testosterone and estradiol was obtained at the end of week 2. Age was a strong predictor of LH suppression during testosterone replacement (r = -0.46), and the effect could not be explained by obesity, SHBG, or higher levels of total or non-SHBG testosterone or estradiol during treatment. In fact, both LH and non-SHBG testosterone levels were lower (P < .05) in older men receiving testosterone treatment. In addition, the strongest association overall was between the percentage decline in LH and non-SHBG estradiol concentrations (r = -0.39). These data provide further evidence that suppression of LH secretion during testosterone treatment is greater as men age, and are consistent with the hypothesis that the hypogonadism of aging men is partly due to a change in gonadotropin negative feedback regulation. These results further suggest that estrogen receptor signaling might contribute to this effect.

OBJECTIVES:The effects of dietary intake of antioxidant vitamins on breast cancer risk are inconclusive. Moreover, little is known as to whether associations differ between non-Hispanic White (NHW) and Hispanic women. We assessed the associations of the dietary intake of antioxidant vitamins commonly found in fruits and vegetables with breast cancer risk and estrogen receptor (ER) status among NHW and Hispanic women living in the Southwestern U.S.MATERIALS AND METHODS:Primary breast cancer cases in the 4-Corners region (Arizona, Colorado, New Mexico, Utah), diagnosed between October 1999 and May 2004, were identified through state cancer registries. Controls were frequency matched by ethnicity and age (+/-5 years). Information on demographic characteristics and other breast cancer risk factors prior to the referent year were collected by interviewer-administered computerized questionnaire. A modified extensive diet history questionnaire was used to assess dietary intake.RESULTS:We did not find a protective effect of dietary antioxidants, such as alpha or beta-carotene, beta-cryptoxanthin, lutein/zeaxanthin, lycopene, retinol, vitamin C, alpha, delta, beta or gamma-tocopherol, on breast cancer risk in populations living in the Southwest. We did not find any consistent associations with multivariate risk of breast cancer or estrogen receptor status. Cigarette smoking was not a significant effect modifier of these associations.CONCLUSION:This case-control study did not find any meaningful association of the dietary intake of antioxidant vitamins with breast cancer risk or ER status.

The obesity epidemic is a global issue and shows no signs of abating, while the cause of this epidemic remains unclear. Marketing practices of energy-dense foods and institutionally-driven declines in physical activity are the alleged perpetrators for the epidemic, despite a lack of solid evidence to demonstrate their causal role. While both may contribute to obesity, we call attention to their unquestioned dominance in program funding and public efforts to reduce obesity, and propose several alternative putative contributors that would benefit from equal consideration and attention. Evidence for microorganisms, epigenetics, increasing maternal age, greater fecundity among people with higher adiposity, assortative mating, sleep debt, endocrine disruptors, pharmaceutical iatrogenesis, reduction in variability of ambient temperatures, and intrauterine and intergenerational effects as contributing factors to the obesity epidemic are reviewed herein. While the evidence is strong for some contributors such as pharmaceutical-induced weight gain, it is still emerging for other reviewed factors. Considering the role of such putative etiological factors of obesity may lead to comprehensive, cause specific, and effective strategies for prevention and treatment of this global epidemic.

Objective: To evaluate the association between BMI (kg/m 2 ) and headaches among women. Methods and Procedures: Cross‐sectional analysis of 11 datasets identified after searching for all large publicly available epidemiologic cohort study datasets containing relevant variables. Datasets included National Health Interview Survey (NHIS): 1997–2003, the first National Health Examination and Nutrition Survey, Alameda County Health Study (ACHS), Tecumseh Community Health Study (TCHS), and Women's Health Initiative (WHI). The women (220,370 in total) were aged 18 years or older and had reported their headache or migraine status. Results: Using nonlinear regression techniques and models adjusted for age, race, and smoking, we found that increased BMI was generally associated with increased likelihood of headache or severe headache among women. A BMI of ∼20 was associated with the lowest risk of headache. Relative to a BMI of 20, mild obesity (BMI of 30) was associated with roughly a 35% increase in the odds for experiencing headache whereas severe obesity (BMI of 40) was associated with roughly an 80% increase in odds. Results were essentially unchanged when models were further adjusted for socioeconomic variables, alcohol consumption, and hypertension. Being diagnosed with migraine showed no association with BMI. Discussion: Among US women, a BMI of ∼20 (about the 5th percentile) was associated with the lowest likelihood of headache. Consistently across studies, obese women had significantly increased risk for headache. By contrast, the risk for diagnosed migraine headache per se was not obviously related to BMI. The direction of causation and mechanisms of action remain to be determined.

Inhibin-B is a heterodimeric glycoprotein produced by Sertoli cells. Although inhibin-B levels are low when seminiferous tubules are damaged, studies in normal monkeys reveal that inhibin-B levels also correlate positively with Sertoli cell number. In this study, we measured inhibin-B levels in healthy young adult men aged 18-24 years and in prepubertal boys aged 5-9 years in relation to body mass index (BMI). Inhibin-B levels declined with increasing obesity in young adult men; values were 26% lower in men who were obese compared to normal-weight men. Sex hormone-binding globulin and total testosterone, but not free testosterone, were also lower with increasing BMI; serum follicle-stimulating hormone and luteinizing hormone levels were unaffected by obesity. In prepubertal boys, by contrast, inhibin-B was unaffected by obesity. We propose that reduced levels of inhibin-B indicate that obese men have fewer Sertoli cells than men of normal weight. Moreover, normal values in obese prepubertal boys suggest that the effect of obesity on inhibin-B is established during puberty. Finally, because each Sertoli cell is thought to support a finite number of germ cells, fewer Sertoli cells in obesity may predispose to a lower sperm count in adulthood. We speculate that the escalating prevalence of obesity and insulin resistance among adolescents might negatively influence male reproductive function for the next generation.

In this chapter we provide an overview of basic statistical concepts and procedures that are germane to researchers interested in aging. We include discussions of hypothesis testing, research design, statistical power, data collection, statistical significance, parametric and nonparametric statistical methods, and choosing an appropriate statistical test. We also provide brief introductions to the different types of data (categorical versus continuous), summary statistics, and a selection of parametric and nonparametric statistical tests including t-tests, analysis of variance, ordinary least squares regression, logistic regression, and survival analysis. We place special emphasis on statistics for maximum lifespan using the example of animal research on caloric restriction. We also include discussions of the major methods of significance testing for statistics of maximum lifespan. We conclude the chapter by offering a series of recommendations that will greatly increase the chances of conducting a valid statistical analysis.

Several theoretical studies have suggested that large samples of randomly ascertained siblings can be used to ascertain phenotypically extreme individuals and thereby increase power to detect genetic linkage in complex traits. Here, we report a genetic linkage scan using extremely discordant and concordant sibling pairs, selected from 34,580 sibling pairs in the southwest of England who completed a personality questionnaire. We performed a genomewide scan for quantitative-trait loci (QTLs) that influence variation in the personality trait of neuroticism, or emotional stability, and we established genomewide empirical significance thresholds by simulation. The maximum pointwise P values, expressed as the negative logarithm (base 10), were found on 1q (3.95), 4q (3.84), 7p (3.90), 12q (4.74), and 13q (3.81). These five loci met or exceeded the 5% genomewide significance threshold of 3.8 (negative logarithm of the P value). QTLs on chromosomes 1, 12, and 13 are likely to be female specific. One locus, on chromosome 1, is syntenic with that reported from QTL mapping of rodent emotionality, an animal model of neuroticism, suggesting that some animal and human QTLs influencing emotional stability may be homologous.