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Breast cancer prevention is of great importance to reduce high incidence in South Africa. This study aimed to investigate adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Cancer Prevention Recommendations and the association with breast cancer risk in black urban women from Soweto, South Africa. A total of 396 breast cancer cases and 396 population-based controls from the South African Breast Cancer study (SABC) matched on age and demographic settings were included. Validated questionnaires were used to collect dietary and epidemiological data. To assess adherence to these recommendations, an eight-point adherence score was developed, using tertiles among controls for scoring each recommendation (0, 0·5 and 1) with zero indicating the lowest adherence to the recommendations. OR and 95 % CI were estimated using multivariate logistic regression models to analyse associations between the WCRF/AICR score and breast cancer risk. Greater adherence (>4·5 v. <3·25) to the 2018 WCRF/AICR Cancer Prevention Recommendations was associated with a significant inverse association with breast cancer risk overall (OR = 0·54, 95 % CI 0·35, 0·91) and specifically in postmenopausal women (OR = 0·55, 95 % CI 0·34, 0·95), in cases with oestrogen positive and progesterone positive breast cancer subtypes (OR = 0·54, 95 % CI 0·39, 0·89 and OR = 0·68, 95 % CI 0·43, 0·89, respectively) and in obese women (OR = 0·52, 95 % CI 0·35, 0·81). No significant association with breast cancer risk was observed in premenopausal women. Greater adherence to the 2018 WCRF/AICR Cancer Prevention Recommendations may reduce breast cancer risk in this black urban population of Soweto. Adherence thereof should be encouraged and form a part of cost-effective breast cancer prevention guidelines.

Background: We investigated whether associations between prevalent diabetes and cancer risk are pertinent to older adults and whether associations differ across subgroups of age, body weight status or levels of physical activity., Methods: We harmonised data from seven prospective cohort studies of older individuals in Europe and the United States participating in the CHANCES consortium. Cox proportional hazard regression was used to estimate the associations of prevalent diabetes with cancer risk (all cancers combined, and for colorectum, prostate and breast). We calculated summary risk estimates across cohorts using pooled analysis and random-effects meta-analysis., Results: A total of 667,916 individuals were included with an overall median (P25-P75) age at recruitment of 62.3 (57-67) years. During a median follow-up time of 10.5 years, 114,404 total cancer cases were ascertained. Diabetes was not associated with the risk of all cancers combined (hazard ratio (HR) = 0.94; 95% confidence interval (CI): 0.86-1.04; I 2  = 63.3%). Diabetes was positively associated with colorectal cancer risk in men (HR = 1.17; 95% CI: 1.08-1.26; I 2  = 0%) and a similar HR in women (1.13; 95% CI: 0.82-1.56; I 2  = 46%), but with a confidence interval including the null. Diabetes was inversely associated with prostate cancer risk (HR = 0.81; 95% CI: 0.77-0.85; I 2  = 0%), but not with postmenopausal breast cancer (HR = 0.96; 95% CI: 0.89-1.03; I 2  = 0%). In exploratory subgroup analyses, diabetes was inversely associated with prostate cancer risk only in men with overweight or obesity., Conclusions: Prevalent diabetes was positively associated with colorectal cancer risk and inversely associated with prostate cancer risk in older Europeans and Americans.

Importance: An improved model for risk stratification can be useful for guiding public health strategies of breast cancer prevention., Objective: To evaluate combined risk stratification utility of common low penetrant single nucleotide polymorphisms (SNPs) and epidemiologic risk factors., Design, Setting, and Participants: Using a total of 17 171 cases and 19 862 controls sampled from the Breast and Prostate Cancer Cohort Consortium (BPC3) and 5879 women participating in the 2010 National Health Interview Survey, a model for predicting absolute risk of breast cancer was developed combining information on individual level data on epidemiologic risk factors and 24 genotyped SNPs from prospective cohort studies, published estimate of odds ratios for 68 additional SNPs, population incidence rate from the National Cancer Institute-Surveillance, Epidemiology, and End Results Program cancer registry and data on risk factor distribution from nationally representative health survey. The model is used to project the distribution of absolute risk for the population of white women in the United States after adjustment for competing cause of mortality., Exposures: Single nucleotide polymorphisms, family history, anthropometric factors, menstrual and/or reproductive factors, and lifestyle factors., Main Outcomes and Measures: Degree of stratification of absolute risk owing to nonmodifiable (SNPs, family history, height, and some components of menstrual and/or reproductive history) and modifiable factors (body mass index [BMI; calculated as weight in kilograms divided by height in meters squared], menopausal hormone therapy [MHT], alcohol, and smoking)., Results: The average absolute risk for a 30-year-old white woman in the United States developing invasive breast cancer by age 80 years is 11.3%. A model that includes all risk factors provided a range of average absolute risk from 4.4% to 23.5% for women in the bottom and top deciles of the risk distribution, respectively. For women who were at the lowest and highest deciles of nonmodifiable risks, the 5th and 95th percentile range of the risk distribution associated with 4 modifiable factors was 2.9% to 5.0% and 15.5% to 25.0%, respectively. For women in the highest decile of risk owing to nonmodifiable factors, those who had low BMI, did not drink or smoke, and did not use MHT had risks comparable to an average woman in the general population., Conclusions and Relevance: This model for absolute risk of breast cancer including SNPs can provide stratification for the population of white women in the United States. The model can also identify subsets of the population at an elevated risk that would benefit most from risk-reduction strategies based on altering modifiable factors. The effectiveness of this model for individual risk communication needs further investigation.

Obesity is a global concern, affecting both developed and developing countries. Although there are large variations in obesity and breast cancer rates worldwide and across racial/ethnic groups, most studies evaluating the impact of obesity on breast cancer risk and survival have been conducted in non-Hispanic white women in the United States or Europe. Given the known racial/ethnic differences in tumor hormone receptor subtype distribution, obesity prevalence, and risk factor profiles, we reviewed published data for women of African, Hispanic, and Asian ancestry in the United States and their countries of origin. Although the data are limited, current evidence suggests a stronger adverse effect of obesity on breast cancer risk and survival in women of Asian ancestry. For African Americans and Hispanics, the strength of the associations appears to be more comparable to that of non-Hispanic whites, particularly when accounting for subtype and menopausal status. Central obesity seems to have a stronger impact in African-American women than general adiposity as measured by body mass index. International data from countries undergoing economic transition offer a unique opportunity to evaluate the impact of rapid weight gain on breast cancer. Such studies should take into account genetic ancestry, which may help elucidate differences in associations between ethnically admixed populations. Overall, additional large studies that use a variety of adiposity measures are needed, because the current evidence is based on few studies, most with limited statistical power. Future investigations of obesity biomarkers will be useful to understand possible racial/ethnic biological differences underlying the complex association between obesity and breast cancer development and progression., (© 2015 American Society for Nutrition.)

Background: Asthma is a complex disease with both genetic and environmental causes. Genome-wide association studies of asthma have mostly involved European populations, and replication of positive associations has been inconsistent., Objective: We sought to identify asthma-associated genes in a large Latino population with genome-wide association analysis and admixture mapping., Methods: Latino children with asthma (n = 1893) and healthy control subjects (n = 1881) were recruited from 5 sites in the United States: Puerto Rico, New York, Chicago, Houston, and the San Francisco Bay Area. Subjects were genotyped on an Affymetrix World Array IV chip. We performed genome-wide association and admixture mapping to identify asthma-associated loci., Results: We identified a significant association between ancestry and asthma at 6p21 (lowest P value: rs2523924, P < 5 × 10(-6)). This association replicates in a meta-analysis of the EVE Asthma Consortium (P = .01). Fine mapping of the region in this study and the EVE Asthma Consortium suggests an association between PSORS1C1 and asthma. We confirmed the strong allelic association between SNPs in the 17q21 region and asthma in Latinos (IKZF3, lowest P value: rs90792, odds ratio, 0.67; 95% CI, 0.61-0.75; P = 6 × 10(-13)) and replicated associations in several genes that had previously been associated with asthma in genome-wide association studies., Conclusions: Admixture mapping and genome-wide association are complementary techniques that provide evidence for multiple asthma-associated loci in Latinos. Admixture mapping identifies a novel locus on 6p21 that replicates in a meta-analysis of several Latino populations, whereas genome-wide association confirms the previously identified locus on 17q21., (Published by Mosby, Inc.)

Purpose: Human papillomavirus type 16 (HPV16) infection is causing an increasing number of oropharyngeal cancers in the United States and Europe. The aim of our study was to investigate whether HPV antibodies are associated with head and neck cancer risk when measured in prediagnostic sera., Methods: We identified 638 participants with incident head and neck cancers (patients; 180 oral cancers, 135 oropharynx cancers, and 247 hypopharynx/larynx cancers) and 300 patients with esophageal cancers as well as 1,599 comparable controls from within the European Prospective Investigation Into Cancer and Nutrition cohort. Prediagnostic plasma samples from patients (collected, on average, 6 years before diagnosis) and control participants were analyzed for antibodies against multiple proteins of HPV16 as well as HPV6, HPV11, HPV18, HPV31, HPV33, HPV45, and HPV52. Odds ratios (ORs) of cancer and 95% CIs were calculated, adjusting for potential confounders. All-cause mortality was evaluated among patients using Cox proportional hazards regression., Results: HPV16 E6 seropositivity was present in prediagnostic samples for 34.8% of patients with oropharyngeal cancer and 0.6% of controls (OR, 274; 95% CI, 110 to 681) but was not associated with other cancer sites. The increased risk of oropharyngeal cancer among HPV16 E6 seropositive participants was independent of time between blood collection and diagnosis and was observed more than 10 years before diagnosis. The all-cause mortality ratio among patients with oropharyngeal cancer was 0.30 (95% CI, 0.13 to 0.67), for patients who were HPV16 E6 seropositive compared with seronegative., Conclusion: HPV16 E6 seropositivity was present more than 10 years before diagnosis of oropharyngeal cancers.

Background: IgE is both a marker and mediator of allergic inflammation. Despite reported differences in serum total IgE levels by race-ethnicity, African American and Latino subjects have not been well represented in genetic studies of total IgE., Objective: We sought to identify the genetic predictors of serum total IgE levels., Methods: We used genome-wide association data from 4292 subjects (2469 African Americans, 1564 European Americans, and 259 Latinos) in the EVE Asthma Genetics Consortium. Tests for association were performed within each cohort by race-ethnic group (ie, African American, Latino, and European American) and asthma status. The resulting P values were meta-analyzed, accounting for sample size and direction of effect. Top single nucleotide polymorphism associations from the meta-analysis were reassessed in 6 additional cohorts comprising 5767 subjects., Results: We identified 10 unique regions in which the combined association statistic was associated with total serum IgE levels (P<5.0×10(-6)) and the minor allele frequency was 5% or greater in 2 or more population groups. Variant rs9469220, corresponding to HLA-DQB1, was the single nucleotide polymorphism most significantly associated with serum total IgE levels when assessed in both the replication cohorts and the discovery and replication sets combined (P=.007 and 2.45×10(-7), respectively). In addition, findings from earlier genome-wide association studies were also validated in the current meta-analysis., Conclusion: This meta-analysis independently identified a variant near HLA-DQB1 as a predictor of total serum IgE levels in multiple race-ethnic groups. This study also extends and confirms the findings of earlier genome-wide association analyses in African American and Latino subjects., (Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Background: Genome-wide association studies of asthma have implicated many genetic risk factors, with well-replicated associations at approximately 10 loci that account for only a small proportion of the genetic risk., Objectives: We aimed to identify additional asthma risk loci by performing an extensive replication study of the results from the EVE Consortium meta-analysis., Methods: We selected 3186 single nucleotide polymorphisms for replication based on the P values from the EVE Consortium meta-analysis. These single nucleotide polymorphisms were genotyped in ethnically diverse replication samples from 9 different studies, totaling 7202 cases, 6426 controls, and 507 case-parent trios. Association analyses were conducted within each participating study, and the resulting test statistics were combined in a meta-analysis., Results: Two novel associations were replicated in European Americans: rs1061477 in the KLK3 gene on chromosome 19 (combined odds ratio = 1.18; 95% CI, 1.10-1.25) and rs9570077 (combined odds ratio =1.20; 95% CI, 1.12-1.29) on chromosome 13q21. We could not replicate any additional associations in the African Americans or Latinos., Conclusions: This extended replication study identified 2 additional asthma risk loci in populations of European descent. The absence of additional loci for African Americans and Latinos highlights the difficulty in replicating associations in admixed populations., (Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Rationale: Although cigarette smoking is the most important cause of chronic obstructive pulmonary disease (COPD), a substantial proportion of COPD cases cannot be explained by smoking alone., Objectives: To evaluate the risk factors for COPD besides personal cigarette smoking., Methods: We constituted an ad hoc subcommittee of the American Thoracic Society Environmental and Occupational Health Assembly. An international group of members was invited, based on their scientific expertise in a specific risk factor for COPD. For each risk factor area, the committee reviewed the literature, summarized the evidence, and developed conclusions about the likelihood of it causing COPD. All conclusions were based on unanimous consensus., Measurements and Main Results: The population-attributable fraction for smoking as a cause of COPD ranged from 9.7 to 97.9%, but was less than 80% in most studies, indicating a substantial burden of disease attributable to nonsmoking risk factors. On the basis of our review, we concluded that specific genetic syndromes and occupational exposures were causally related to the development of COPD. Traffic and other outdoor pollution, secondhand smoke, biomass smoke, and dietary factors are associated with COPD, but sufficient criteria for causation were not met. Chronic asthma and tuberculosis are associated with irreversible loss of lung function, but there remains uncertainty about whether there are important phenotypic differences compared with COPD as it is typically encountered in clinical settings., Conclusions: In public health terms, a substantive burden of COPD is attributable to risk factors other than smoking. To prevent COPD-related disability and mortality, efforts must focus on prevention and cessation of exposure to smoking and these other, less well-recognized risk factors.

In the United States, among Hispanics, Mexican Americans have the lowest rate of asthma. However, this population includes Mexican Americans born in the United States and in Mexico, and risk factors that might impact the prevalence of asthma differ between these groups. To determine the prevalence of and risk factors for asthma among U.S.- and Mexican-born Mexican Americans, we analyzed data from two U.S. surveys that included 4,574 persons who self-reported their ethnicity as Mexican American from the Third National Health and Nutrition Examination Survey (NHANES III) 1998-1994 and 12,980 persons who self-reported their ethnicity as Mexican American from National Health Interview Survey (NHIS) 1997-2001. U.S.-born Mexican Americans were more likely than Mexican-born Mexican Americans to report ever having asthma in both the NHANES III (7% [SE 0.5] vs. 3% [SE 0.3], p < 0.001) and NHIS surveys (8.1% [0.4] vs. 2.5% [0.2], p < 0.001). In a multivariate regression model controlling for multiple demographic variables and health care, the risk for asthma was higher among U.S.-born Mexicans in NHANES III (odds ratio 2.1, 95% confidence interval 1.4-3.3) and NHIS (odds ratio 2.7, 95% confidence interval 1.6-5.5). In conclusion, the prevalence of asthma was higher in U.S.-born than in Mexican-born Mexican Americans. This finding highlights the importance of environmental exposures in developing asthma in a migratory population.

Background: The impact of outdoor air pollution on infant mortality has not been quantified., Methods: Based on exposure-response functions from a U.S. cohort study, we assessed the attributable risk of postneonatal infant mortality in 23 U.S. metropolitan areas related to particulate matter <10 microm in diameter (PM10) as a surrogate of total air pollution., Results: The estimated proportion of all cause mortality, sudden infant death syndrome (normal birth weight infants only) and respiratory disease mortality (normal birth weight) attributable to PM10 above a chosen reference value of 12.0 microg/m3 PM10 was 6% (95% confidence interval 3-11%), 16% (95% confidence interval 9-23%) and 24% (95% confidence interval 7-44%), respectively. The expected number of infant deaths per year in the selected areas was 106 (95% confidence interval 53-185), 79 (95% confidence interval 46-111) and 15 (95% confidence interval 5-27), respectively. Approximately 75% of cases were from areas where the current levels are at or below the new U.S. PM2.5 standard of 15 microg/m3 (equivalent to 25 microg/m3 PM10). In a country where infant mortality rates and air pollution levels are relatively low, ambient air pollution as measured by particulate matter contributes to a substantial fraction of infant death, especially for those due to sudden infant death syndrome and respiratory disease. Even if all counties would comply to the new PM2.5 standard, the majority of the estimated burden would remain., Conclusion: Given the inherent limitations of risk assessments, further studies are needed to support and quantify the relationship between infant mortality and air pollution.

Climate change may affect exposures to air pollutants by affecting weather, anthropogenic emissions, and biogenic emissions and by changing the distribution and types of airborne allergens. Local temperature, precipitation, clouds, atmospheric water vapor, wind speed, and wind direction influence atmospheric chemical processes, and interactions occur between local and global-scale environments. If the climate becomes warmer and more variable, air quality is likely to be affected. However, the specific types of change (i.e., local, regional, or global), the direction of change in a particular location (i.e., positive or negative), and the magnitude of change in air quality that may be attributable to climate change are a matter of speculation, based on extrapolating present understanding to future scenarios. There is already extensive evidence on the health effects of air pollution. Ground-level ozone can exacerbate chronic respiratory diseases and cause short-term reductions in lung function. Exposure to particulate matter can aggravate chronic respiratory and cardiovascular diseases, alter host defenses, damage lung tissue, lead to premature death, and possibly contribute to cancer. Health effects of exposures to carbon monoxide, sulfur dioxide, and nitrogen dioxide can include reduced work capacity, aggravation of existing cardiovascular diseases, effects on pulmonary function, respiratory illnesses, lung irritation, and alterations in the lung's defense systems. Adaptations to climate change should include ensuring responsiveness of air quality protection programs to changing pollution levels. Research needs include basic atmospheric science work on the association between weather and air pollutants; improving air pollution models and their linkage with climate change scenarios; and closing gaps in the understanding of exposure patterns and health effects.

We examined the potential impacts of climate variability and change on human health as part of a congressionally mandated study of climate change in the United States. Our author team, comprising experts from academia, government, and the private sector, was selected by the federal interagency U.S. Global Change Research Program, and this report stems from our first 18 months of work. For this assessment we used a set of assumptions and/or projections of future climates developed for all participants in the National Assessment of the Potential Consequences of Climate Variability and Change. We identified five categories of health outcomes that are most likely to be affected by climate change because they are associated with weather and/or climate variables: temperature-related morbidity and mortality; health effects of extreme weather events (storms, tornadoes, hurricanes, and precipitation extremes); air-pollution-related health effects; water- and foodborne diseases; and vector- and rodent-borne diseases. We concluded that the levels of uncertainty preclude any definitive statement on the direction of potential future change for each of these health outcomes, although we developed some hypotheses. Although we mainly addressed adverse health outcomes, we identified some positive health outcomes, notably reduced cold-weather mortality, which has not been extensively examined. We found that at present most of the U.S. population is protected against adverse health outcomes associated with weather and/or climate, although certain demographic and geographic populations are at increased risk. We concluded that vigilance in the maintenance and improvement of public health systems and their responsiveness to changing climate conditions and to identified vulnerable subpopulations should help to protect the U.S. population from any adverse health outcomes of projected climate change.

An outline is presented of progress in the development of health expectancy indicators, which are growing in importance as a means of assessing the health status of populations and determining public health priorities.

Since an original report suggesting a protective effect of oral contraceptives on rheumatoid arthritis incidence, 12 studies from four countries have shown conflicting results. Using the method of DerSimonian and Laird all available studies (including two completed but not as yet published) were evaluated. Overall, the relative risk of oral contraceptive use on the development of RA were less than unity. When summary statistics for case-control studies were examined, a small protective effect was noted, but was not statistically significant.