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Background About 4.5% of new cancer cases affect adolescent and young adult aged between 15 and 39 years in the United States (US). However, the effect of neuropsychiatric conditions on long‐term adolescent and young adult cancer (AYAC) survivors has not been formally investigated. Thus, the impact and management of late neuropsychiatric complications in AYAC survivors compared to non‐cancer‐matched controls (NCMC) in the US were evaluated using the All of Us (AoU) Research Program. Methods Participants in the AoU Controlled Tier Dataset (v6) diagnosed with cancer between ages 15 and 39 were identified from electronic health records and surveys. AYAC survivors were matched with NCMC using the optimal pair‐matching algorithm at a 1:4 ratio. Data on past diagnoses, current follow‐up care, and treatment patterns of neuropsychiatric complications were collected. Results Analysis was performed on 788 AYAC survivors and 3152 NCMC. AYAC survivors, with an average of 8.8 years since their first cancer diagnosis, were more likely than NCMC to receive a diagnosis of neuropathy, memory loss and epilepsy (p  < 0.001). Survivors also had a higher rate of follow‐up care and treatment utilization for these neurological conditions compared to NCMC (p  < 0.05). Treatment utilization was highest among survivors receiving care for epilepsy (88%), and lower for neuropathy (70%), memory loss (61%), and chronic fatigue (59%). Conclusions This large study reveals that AYAC survivors, on average 9 years after their cancer diagnosis, require more frequent follow‐up care for neurological complications compared to non‐cancer individuals. However, the management of neuropathy, memory loss, and chronic fatigue is hindered by a lack of mechanism‐based effective therapies.

Endometriosis is a risk factor for epithelial ovarian cancer; however, whether this risk extends to all invasive histological subtypes or borderline tumours is not clear. We undertook an international collaborative study to assess the association between endometriosis and histological subtypes of ovarian cancer. Data from 13 ovarian cancer case–control studies, which were part of the Ovarian Cancer Association Consortium, were pooled and logistic regression analyses were undertaken to assess the association between self-reported endometriosis and risk of ovarian cancer. Analyses of invasive cases were done with respect to histological subtypes, grade, and stage, and analyses of borderline tumours by histological subtype. Age, ethnic origin, study site, parity, and duration of oral contraceptive use were included in all analytical models. 13 226 controls and 7911 women with invasive ovarian cancer were included in this analysis. 818 and 738, respectively, reported a history of endometriosis. 1907 women with borderline ovarian cancer were also included in the analysis, and 168 of these reported a history of endometriosis. Self-reported endometriosis was associated with a significantly increased risk of clear-cell (136 [20·2%] of 674 cases vs 818 [6·2%] of 13 226 controls, odds ratio 3·05, 95% CI 2·43–3·84, p<0·0001), low-grade serous (31 [9·2%] of 336 cases, 2·11, 1·39–3·20, p<0·0001), and endometrioid invasive ovarian cancers (169 [13·9%] of 1220 cases, 2·04, 1·67–2·48, p<0·0001). No association was noted between endometriosis and risk of mucinous (31 [6·0%] of 516 cases, 1·02, 0·69–1·50, p=0·93) or high-grade serous invasive ovarian cancer (261 [7·1%] of 3659 cases, 1·13, 0·97–1·32, p=0·13), or borderline tumours of either subtype (serous 103 [9·0%] of 1140 cases, 1·20, 0·95–1·52, p=0·12, and mucinous 65 [8·5%] of 767 cases, 1·12, 0·84–1·48, p=0·45). Clinicians should be aware of the increased risk of specific subtypes of ovarian cancer in women with endometriosis. Future efforts should focus on understanding the mechanisms that might lead to malignant transformation of endometriosis so as to help identify subsets of women at increased risk of ovarian cancer. Ovarian Cancer Research Fund, National Institutes of Health, California Cancer Research Program, California Department of Health Services, Lon V Smith Foundation, European Community's Seventh Framework Programme, German Federal Ministry of Education and Research of Germany, Programme of Clinical Biomedical Research, German Cancer Research Centre, Eve Appeal, Oak Foundation, UK National Institute of Health Research, National Health and Medical Research Council of Australia, US Army Medical Research and Materiel Command, Cancer Council Tasmania, Cancer Foundation of Western Australia, Mermaid 1, Danish Cancer Society, and Roswell Park Alliance Foundation.

Pooled data from 19 prospective studies showed that after adjustments for age, physical activity, alcohol consumption, education, and marital status, both overweight and obesity were associated with increased mortality, which was lowest with a BMI between 20 and 25. Two thirds of the adult population in the United States and at least half the populations of many other developed countries are currently overweight or obese. 1 , 2 Although it is well established that obese people — defined as having a body-mass index (BMI) (the weight in kilograms divided by the square of the height in meters) of 30.0 or more — have increased death rates from heart disease, stroke, and many specific cancers, 3 the strength of the relationship between a high BMI and all-cause mortality remains uncertain, as does the optimal BMI with respect to mortality. Some studies suggest that . . .

The prevalence of class III obesity (body mass index [BMI]≥40 kg/m2) has increased dramatically in several countries and currently affects 6% of adults in the US, with uncertain impact on the risks of illness and death. Using data from a large pooled study, we evaluated the risk of death, overall and due to a wide range of causes, and years of life expectancy lost associated with class III obesity. In a pooled analysis of 20 prospective studies from the United States, Sweden, and Australia, we estimated sex- and age-adjusted total and cause-specific mortality rates (deaths per 100,000 persons per year) and multivariable-adjusted hazard ratios for adults, aged 19-83 y at baseline, classified as obese class III (BMI 40.0-59.9 kg/m2) compared with those classified as normal weight (BMI 18.5-24.9 kg/m2). Participants reporting ever smoking cigarettes or a history of chronic disease (heart disease, cancer, stroke, or emphysema) on baseline questionnaires were excluded. Among 9,564 class III obesity participants, mortality rates were 856.0 in men and 663.0 in women during the study period (1976-2009). Among 304,011 normal-weight participants, rates were 346.7 and 280.5 in men and women, respectively. Deaths from heart disease contributed largely to the excess rates in the class III obesity group (rate differences = 238.9 and 132.8 in men and women, respectively), followed by deaths from cancer (rate differences = 36.7 and 62.3 in men and women, respectively) and diabetes (rate differences = 51.2 and 29.2 in men and women, respectively). Within the class III obesity range, multivariable-adjusted hazard ratios for total deaths and deaths due to heart disease, cancer, diabetes, nephritis/nephrotic syndrome/nephrosis, chronic lower respiratory disease, and influenza/pneumonia increased with increasing BMI. Compared with normal-weight BMI, a BMI of 40-44.9, 45-49.9, 50-54.9, and 55-59.9 kg/m2 was associated with an estimated 6.5 (95% CI: 5.7-7.3), 8.9 (95% CI: 7.4-10.4), 9.8 (95% CI: 7.4-12.2), and 13.7 (95% CI: 10.5-16.9) y of life lost. A limitation was that BMI was mainly ascertained by self-report. Class III obesity is associated with substantially elevated rates of total mortality, with most of the excess deaths due to heart disease, cancer, and diabetes, and major reductions in life expectancy compared with normal weight. Please see later in the article for the Editors' Summary.

High body mass index (BMI) has become the leading risk factor of disease burden in high-income countries. While recent studies have suggested that the risk of cancer related to obesity is mediated by time, insights into the dose-response relationship and the cumulative impact of overweight and obesity during the life course on cancer risk remain scarce. To our knowledge, this study is the first to assess the impact of adulthood overweight and obesity duration on the risk of cancer in a large cohort of postmenopausal women. Participants from the observational study of the Women's Health Initiative (WHI) with BMI information from at least three occasions during follow-up, free of cancer at baseline, and with complete covariate information were included (n = 73,913). Trajectories of BMI across ages were estimated using a quadratic growth model; overweight duration (BMI ≥ 25 kg/m2), obesity duration (BMI ≥ 30 kg/m2), and weighted cumulative overweight and obese years, which take into account the degree of overweight and obesity over time (a measure similar to pack-years of cigarette smoking), were calculated using predicted BMIs. Cox proportional hazard models were applied to determine the cancer risk associated with overweight and obesity duration. In secondary analyses, the influence of important effect modifiers and confounders, such as smoking status, postmenopausal hormone use, and ethnicity, was assessed. A longer duration of overweight was significantly associated with the incidence of all obesity-related cancers (hazard ratio [HR] per 10-y increment: 1.07, 95% CI 1.06-1.09). For postmenopausal breast and endometrial cancer, every 10-y increase in adulthood overweight duration was associated with a 5% and 17% increase in risk, respectively. On adjusting for intensity of overweight, these figures rose to 8% and 37%, respectively. Risks of postmenopausal breast and endometrial cancer related to overweight duration were much more pronounced in women who never used postmenopausal hormones. This study has limitations because some of the anthropometric information was obtained from retrospective self-reports. Furthermore, data from longitudinal studies with long-term follow-up and repeated anthropometric measures are typically subject to missing data at various time points, which was also the case in this study. Yet, this limitation was partially overcome by using growth curve models, which enabled us to impute data at missing time points for each participant. In summary, this study showed that a longer duration of overweight and obesity is associated with an increased risk of developing several forms of cancer. Furthermore, the degree of overweight experienced during adulthood seemed to play an important role in the risk of developing cancer, especially for endometrial cancer. Although the observational nature of our study precludes inferring causality or making clinical recommendations, our findings suggest that reducing overweight duration in adulthood could reduce cancer risk and that obesity prevention is important from early onset. If this is true, health care teams should recognize the potential of obesity management in cancer prevention and that excess body weight in women is important to manage regardless of the age of the patient.

Background Per- and poly- fluoroalkyl substances (PFASs) are a large family of synthetic chemicals, some of which are mammary toxicants and endocrine disruptors. Their potential as breast carcinogens is unclear. Our objective was to evaluate the risk of breast cancer associated with serum PFAS concentrations in a nested case-control study within the California Teachers Study. Methods Participants were 902 women with invasive breast cancer (cases) and 858 with no such diagnosis (controls) who provided 10 mL of blood and were interviewed during 2011–2015, an average of 35 months after case diagnosis. PFASs were measured using automated online SPE-HPLC-MS/MS methods. Statistical analyses were restricted to six PFASs with detection frequencies ≥ 95%: PFOA (Perfluorooctanoic acid), PFNA (Perfluorononanoic acid), PFUnDA (Perfluoroundecanoic acid), PFHxS (Perfluorohexane sulfonic acid), PFOS (Perfluorooctane sulfonic acid), and MeFOSAA (2-(N-Methyl-perfluorooctane sulfonamido) acetic acid. Unconditional logistic regression was used to calculate adjusted odds ratios (ORs), estimating the breast cancer risk associated with each PFAS. Results For all cases of invasive breast cancer, none of the adjusted ORs were statistically significant but marginally significant ORs < 1.0 were observed for PFUnDA and PFHxS (p-trend = 0.08). Adjusted ORs < 1.0 for PFUnDA and PFHxS were statistically significant ( p  ≤ 0.05) among the 107 cases with hormone-negative tumors but not the 743 with hormone-positive tumors. Conclusion Overall, these findings do not provide evidence that serum PFAS levels measured after diagnosis are related to breast cancer risk. The few inverse associations found may be due to chance or may be artifacts of study design. Future studies should incorporate information about genetic susceptibility, endogenous estrogen levels, and measurements of PFASs prior to diagnosis and treatment.

There are few medical issues that have generated as much controversy as screening for breast cancer. In science, controversy often stimulates innovation; however, the intensely divisive debate over mammographic screening has had the opposite effect and has stifled progress. The same two questions—whether it is better to screen annually or bi-annually, and whether women are best served by beginning screening at 40 or some later age—have been debated for 20 years, based on data generated three to four decades ago. The controversy has continued largely because our current approach to screening assumes all women have the same risk for the same type of breast cancer. In fact, we now know that cancers vary tremendously in terms of timing of onset, rate of growth, and probability of metastasis. In an era of personalized medicine, we have the opportunity to investigate tailored screening based on a woman’s specific risk for a specific tumor type, generating new data that can inform best practices rather than to continue the rancorous debate. It is time to move from debate to wisdom by asking new questions and generating new knowledge. The WISDOM Study (Women Informed to Screen Depending On Measures of risk) is a pragmatic, adaptive, randomized clinical trial comparing a comprehensive risk-based, or personalized approach to traditional annual breast cancer screening. The multicenter trial will enroll 100,000 women, powered for a primary endpoint of non-inferiority with respect to the number of late stage cancers detected. The trial will determine whether screening based on personalized risk is as safe, less morbid, preferred by women, will facilitate prevention for those most likely to benefit, and adapt as we learn who is at risk for what kind of cancer. Funded by the Patient Centered Outcomes Research Institute, WISDOM is the product of a multi-year stakeholder engagement process that has brought together consumers, advocates, primary care physicians, specialists, policy makers, technology companies and payers to help break the deadlock in this debate and advance towards a new, dynamic approach to breast cancer screening.

Background The debate continues among medical professionals regarding the frequency, starting age, and stopping age for mammography screening. Some experts suggest tailoring recommendations based on individuals’ personal breast cancer risk. Previous studies have not compared the impact of annual versus biennial mammography stratified by age group and risk category. The purpose of this study was to examine the relationship between mammography frequency and mortality by age group and risk category in the California Teachers Study. Methods Using data from study questionnaires from 93,438 women between the ages of 40 and 85 and linkages to the California Cancer Registry and other indices, overall and breast cancer-specific mortality by mammography frequency were estimated using multivariable Cox proportional hazards models, stratified by age group and risk category at baseline as determined by the Gail breast cancer risk model. Results During the follow-up period of 20 years, overall mortality risk was lower in women who had annual or biennial mammography compared to less frequent or no mammography in all age groups. Annual mammography was associated with lower overall mortality risk compared to biennial mammography among women age 50–85. This difference was especially apparent in women age 60–74, regardless of estimated Gail risk category at baseline. Breast cancer-specific mortality was lower among women who had annual mammography compared to biennial or less frequent mammography among women age 60–74, regardless of their baseline risk. Conclusions Our findings suggest that at least biennial mammography is beneficial to most women age 40–85 and that annual mammography is more beneficial than biennial mammography to most women age 50–85 in terms of overall mortality.

Foodborne illness is prevented by inspection and surveillance conducted by health departments across America. Appropriate restaurant behavior is enforced and monitored via public health inspections. However, surveillance coverage provided by state and local health departments is insufficient in preventing the rising number of foodborne illness outbreaks. To address this need for improved surveillance coverage we conducted a supplementary form of public health surveillance using social media data: Yelp.com restaurant reviews in the city of San Francisco. Yelp is a social media site where users post reviews and rate restaurants they have personally visited. Presence of keywords related to health code regulations and foodborne illness symptoms, number of restaurant reviews, number of Yelp stars, and restaurant price range were included in a model predicting a restaurant's likelihood of health code violation measured by the assigned San Francisco public health code rating. For a list of major health code violations see (S1 Table). We built the predictive model using 71,360 Yelp reviews of restaurants in the San Francisco Bay Area. The predictive model was able to predict health code violations in 78% of the restaurants receiving serious citations in our pilot study of 440 restaurants. Training and validation data sets each pulled data from 220 restaurants in San Francisco. Keyword analysis of free text within Yelp not only improved detection of high-risk restaurants, but it also served to identify specific risk factors related to health code violation. To further validate our model we applied the model generated in our pilot study to Yelp data from 1,542 restaurants in San Francisco. The model achieved 91% sensitivity 74% specificity, area under the receiver operator curve of 98%, and positive predictive value of 29% (given a substandard health code rating prevalence of 10%). When our model was applied to restaurant reviews in New York City we achieved 74% sensitivity, 54% specificity, area under the receiver operator curve of 77%, and positive predictive value of 25% (given a prevalence of 12%). Model accuracy improved when reviews ranked highest by Yelp were utilized. Our results indicate that public health surveillance can be improved by using social media data to identify restaurants at high risk for health code violation. Additionally, using highly ranked Yelp reviews improves predictive power and limits the number of reviews needed to generate prediction. Use of this approach as an adjunct to current risk ranking of restaurants prior to inspection may enhance detection of those restaurants participating in high risk practices that may have gone previously undetected. This model represents a step forward in the integration of social media into meaningful public health interventions.

Autophagy has been linked with melanoma risk and survival, but no polymorphisms in autophagy‐related (ATG) genes have been investigated in relation to melanoma progression. We examined five single‐nucleotide polymorphisms (SNPs) in three ATG genes (ATG5; ATG10; and ATG16L) with known or suspected impact on autophagic flux in an international population‐based case–control study of melanoma. DNA from 911 melanoma patients was genotyped. An association was identified between (GG) (rs2241880) and earlier stage at diagnosis (OR 0.47; 95% Confidence Intervals (CI) = 0.27–0.81, P = 0.02) and a decrease in Breslow thickness (P = 0.03). The ATG16L heterozygous genotype (AG) (rs2241880) was associated with younger age at diagnosis (P = 0.02). Two SNPs in ATG5 were found to be associated with increased stage (rs2245214 CG, OR 1.47; 95% CI = 1.11–1.94, P = 0.03; rs510432 CC, OR 1.84; 95% CI = 1.12–3.02, P = 0.05). Finally, we identified inverse associations between ATG5 (GG rs2245214) and melanomas on the scalp or neck (OR 0.20, 95% CI = 0.05–0.86, P = 0.03); ATG10 (CC) (rs1864182) and brisk tumor infiltrating lymphocytes (TILs) (OR 0.42; 95% CI = 0.21–0.88, P = 0.02), and ATG5 (CC) (rs510432) with nonbrisk TILs (OR 0.55; 95% CI = 0.34–0.87, P = 0.01). Our data suggest that ATG SNPs might be differentially associated with specific host and tumor characteristics including age at diagnosis, TILs, and stage. These associations may be critical to understanding the role of autophagy in cancer, and further investigation will help characterize the contribution of these variants to melanoma progression. Autophagy is critical in cancer risk and progression, and inherited variants in autophagy genes have not been investigated in relation to melanoma. In a large population‐based study of melanoma, two SNPs were associated with stage at diagnosis and tumor infiltrating lymphocytes; one SNP was associated with thinner Breslow thickness, earlier stage at diagnosis and younger age of diagnosis. Autophagy SNPs may influence melanoma progression and should be investigated further.