Environment driven changes in type 2 diabetes, overweight and obesity in an isolated Mixe community in the Valley of Oaxaca, southern Mexico.

BACKGROUND: This study focused on type 2 diabetes mellitus (T2DM) in a group of adult Mixe, an Indigenous population from Oaxaca, Mexico. Mixe comprised an estimated 9.4% (n ≅ 90 000) of the Indigenous population in Oaxaca. Mexico. OBJECTIVE: This study focused on a group of adult Mixe, an Indigenous population from Oaxaca, Mexico. To compare the prevalence of T2DM, overweight (OW), obesity (OB), and hypertension (HTN) between 2007 and 2017 for a small, isolated Mixe community in the Valley of Oaxaca, Mexico. We test whether or not environmental changes have affected T2DM prevalence. METHODS AND MATERIALS: Demographic and medical record data were collected in the community in 2007 and 2017 from the medical clinic and the mayor's office. T2DM was medically diagnosed among adults (>34 years old), in 2007 (n = 730) and in 2017 (n = 829). RESULTS: T2DM crude prevalence increased from 6.7% to 12.1% (p < .001) from 2007 to 2017. The mean age of the sample analyzed was 60.6 (SD = 9.7). Age-adjusted T2DM prevalence increased from 6.7% to 10.8% (p < .002). T2DM was 5.7%-5.5% among males (p < .53) and 7.1%-13.6% among females (p < .001). Sex-specific OW and OB simulation studies indicate females had 7% less OW in 2007, and males were unchanged compared with 2017. OB among males and females was significantly higher in 2017 compared with 2007 (increased by 15.2% and 8.3%, males and females, respectively). Sexes combined OW + OB increased 12.7% among males but was unchanged in females (-0.5%). In the sexes combined analysis, OW prevalence increased 12.7% to 27.1% (p < .001) and OB prevalence increased 10.7%-27.9% (p < .001) from 2007 to 2017. HTN did not change significantly from 2007 to 2017 (15.4% and 14.6%, respectively) (p = .63) in adults. Among T2DM individuals, the frequency of HTN was not significantly different in 2007 and 2017 (57.1% and 37%, respectively) (p = .65). Transition to a Western diet consisting of high-carbohydrate foods occurred at the same time as increased T2DM from 2007 to 2017, with a higher prevalence of T2DM noted among females in 2017. CONCLUSIONS: An increased prevalence of T2DM, OW, and OB but not HTN was observed in the Mixe community from 2007 to 2017 and was associated with the adoption of a high-carbohydrate Western diet.

Validity of models for predicting BRCA1 and BRCA2 mutations.

BACKGROUND: Deleterious mutations of the BRCA1 and BRCA2 genes confer susceptibility to breast and ovarian cancer. At least 7 models for estimating the probabilities of having a mutation are used widely in clinical and scientific activities; however, the merits and limitations of these models are not fully understood. OBJECTIVE: To systematically quantify the accuracy of the following publicly available models to predict mutation carrier status: BRCAPRO, family history assessment tool, Finnish, Myriad, National Cancer Institute, University of Pennsylvania, and Yale University. DESIGN: Cross-sectional validation study, using model predictions and BRCA1 or BRCA2 mutation status of patients different from those used to develop the models. SETTING: Multicenter study across Cancer Genetics Network participating centers. PATIENTS: 3 population-based samples of participants in research studies and 8 samples from genetic counseling clinics. MEASUREMENTS: Discrimination between individuals testing positive for a mutation in BRCA1 or BRCA2 from those testing negative, as measured by the c-statistic, and sensitivity and specificity of model predictions. RESULTS: The 7 models differ in their predictions. The better-performing models have a c-statistic around 80%. BRCAPRO has the largest c-statistic overall and in all but 2 patient subgroups, although the margin over other models is narrow in many strata. Outside of high-risk populations, all models have high false-negative and false-positive rates across a range of probability thresholds used to refer for mutation testing. LIMITATION: Three recently published models were not included. CONCLUSIONS: All models identify women who probably carry a deleterious mutation of BRCA1 or BRCA2 with adequate discrimination to support individualized genetic counseling, although discrimination varies across models and populations.

The impact of periconceptional maternal stress on fecundability.

PURPOSE: To examine the association between periconceptional self-reported stress levels and fecundability in women. METHODS: Daily stress was reported on a scale from 1 to 4 (lowest to highest) among 400 women who completed daily diaries including data on lifestyle and behavioral factors, menstrual characteristics, contraceptive use, and intercourse for up to 20 cycles or until pregnancy. Discrete survival analysis was used to estimate the associations between self-reported stress during specific windows of the menstrual cycle and fecundability (cycles at risk until pregnancy), adjusting for potential confounders. RESULTS: One hundred thirty-nine women became pregnant. During the follicular phase, there was a 46% reduction in fecundability for a 1-unit increase in self-reported stress during the estimated ovulatory window (fecundability odds ratio [FOR] = 0.54; 95% confidence interval [CI] 0.35-0.84) and an attenuated trend for the preovulatory window (FOR = 0.73; 95% CI 0.48-1.10). During the luteal phase, higher stress was associated with increased probability of conception (FOR = 1.63, 95% CI 1.07-2.50), possibly due to reverse causality. CONCLUSIONS: Higher stress during the ovulatory window may reduce probability of conception; however, once conception occurs, changes in the hormonal milieu and/or knowledge of the pregnancy may result in increased stress. These findings reinforce the need for encouraging stress management techniques in the aspiring and expecting mother.

Characterization of BRCA1 and BRCA2 mutations in a large United States sample.

PURPOSE: An accurate evaluation of the penetrance of BRCA1 and BRCA2 mutations is essential to the identification and clinical management of families at high risk of breast and ovarian cancer. Existing studies have focused on Ashkenazi Jews (AJ) or on families from outside the United States. In this article, we consider the US population using the largest US-based cohort to date of both AJ and non-AJ families. METHODS: We collected 676 AJ families and 1,272 families of other ethnicities through the Cancer Genetics Network. Two hundred eighty-two AJ families were population based, whereas the remainder was collected through counseling clinics. We used a retrospective likelihood approach to correct for bias induced by oversampling of participants with a positive family history. Our approach takes full advantage of detailed family history information and the Mendelian transmission of mutated alleles in the family. RESULTS: In the US population, the estimated cumulative breast cancer risk at age 70 years was 0.46 (95% CI, 0.39 to 0.54) in BRCA1 carriers and 0.43 (95% CI, 0.36 to 0.51) in BRCA2 carriers, whereas ovarian cancer risk was 0.39 (95% CI, 0.30 to 0.50) in BRCA1 carriers and 0.22 (95% CI, 0.14 to 0.32) in BRCA2 carriers. We also reported the prospective risks of developing cancer for cancer-free carriers in 10-year age intervals. We noted a rapid decrease in the relative risk of breast cancer with age and derived its implication for genetic counseling. CONCLUSION: The penetrance of BRCA mutations in the United States is largely consistent with previous studies on Western populations given the large CIs on existing estimates. However, the absolute cumulative risks are on the lower end of the spectrum.