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Abstract Background Despite strong evidence of an inverse association of physical activity with postmenopausal breast cancer risk, whether a certain intensity or time of life of physical activity is most effective for lowering breast cancer risk is not known. Methods In 118,899 postmenopausal women in the prospective NIH-AARP Diet and Health Study, we examined the relations of light and moderate-to-vigorous intensity physical activity during four periods of life ("historical": ages 15-18, 19-29, 35-39 years; "recent": past 10 years) to postmenopausal breast cancer risk. Physical activity was assessed by self-report at baseline, and 4287 incident breast cancers were identified over 6.6 years of follow-up. Results In age-adjusted and multivariate Cox regression models, >7 hours/week of moderate-to-vigorous activity during the past 10 years was associated with 16% reduced risk of postmenopausal breast cancer (RR:0.84; 95%CI:0.76,0.93) compared with inactivity. The association remained statistically significant after adjustment for BMI (RR:0.87; 95%CI:0.78,0.96). Neither moderate-to-vigorous activity during other periods of life nor light intensity activity during any period of life was related to breast cancer risk, and associations did not vary by tumor characteristics. Conclusion A high level of recent, but not historical, physical activity of moderate-to-vigorous intensity is associated with reduced postmenopausal breast cancer risk. More precise recall of recent physical activity than activity in the distant past is one possible explanation for our findings.

Abstract Background Multidisciplinary attempts to understand the etiology of breast cancer are expanding to increasingly include new potential markers of disease risk. Those efforts may have maximal scientific and practical influence if new findings are placed in context of the well-understood lifestyle and reproductive risk factors or existing risk prediction models for breast cancer. We therefore evaluated known risk factors for breast cancer in a cancer screening trial that does not have breast cancer as a study endpoint but is large enough to provide numerous analytic opportunities for breast cancer. Methods We evaluated risk factors for breast cancer (N = 2085) among 70,575 women who were randomized in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Using Poisson regression, we calculated adjusted relative risks [RRs, with 95% confidence intervals (CIs)] for lifestyle and reproductive factors during an average of 5 years of follow-up from date of randomization. Results As expected, increasing age, nulliparity, positive family history of breast cancer, and use of menopausal hormone therapy were positively associated with breast cancer. Later age at menarche (16 years or older vs. < 12: RR = 0.81, 95% CI, 0.65–1.02) or menopause (55 years or older vs. < 45: RR = 1.29, 95% CI, 1.03–1.62) were less strongly associated with breast cancer than was expected. There were weak positive associations between taller height and heavier weight, and only severe obesity [body mass index (BMI; kg/m2) 35 or more vs. 18.5–24.9: RR = 1.21, 95% CI, 1.02–1.43] was statistically significantly associated with breast cancer. Conclusion The ongoing PLCO trial offers continued opportunities for new breast cancer investigations, but these analyses suggest that the associations between breast cancer and age at menarche, age at menopause, and obesity might be changing as the underlying demographics of these factors change. Clinical Trials Registration http://www.clinicaltrials.gov, NCT00002540.

Although physical activity is an established protective factor for cardiovascular diseases such as ischemic heart disease and stroke, less is known with regard to the association between specific domains of physical activity and heart failure, as well as the association between cardiorespiratory fitness and heart failure. We conducted a systematic review and meta-analysis of prospective observational studies to clarify the relations of total physical activity, domains of physical activity and cardiorespiratory fitness to risk of heart failure. PubMed and Embase databases were searched up to January 14th, 2020. Summary relative risks (RRs) were calculated using random effects models. Twenty-nine prospective studies (36 publications) were included in the review. The summary RRs for high versus low levels were 0.77 (95% CI 0.70–0.85, I2 = 49%, n = 7) for total physical activity, 0.74 (95% CI 0.68–0.81, I2 = 88.1%, n = 16) for leisure-time activity, 0.66 (95% CI 0.59–0.74, I2 = 0%, n = 2) for vigorous activity, 0.81 (95% CI 0.69–0.94, I2 = 86%, n = 3) for walking and bicycling combined, 0.90 (95% CI 0.86–0.95, I2 = 0%, n = 3) for occupational activity, and 0.31 (95% CI 0.19–0.49, I2 = 96%, n = 6) for cardiorespiratory fitness. In dose–response analyses, the summary RRs were 0.89 (95% CI 0.83–0.95, I2 = 67%, n = 4) per 20 MET-hours per day of total activity and 0.71 (95% CI 0.65–0.78, I2 = 85%, n = 11) per 20 MET-hours per week of leisure-time activity. Nonlinear associations were observed in both analyses with a flattening of the dose–response curve at 15–20 MET-hours/week for leisure-time activity. These findings suggest that high levels of total physical activity, leisure-time activity, vigorous activity, occupational activity, walking and bicycling combined and cardiorespiratory fitness are associated with reduced risk of developing heart failure. [ABSTRACT FROM AUTHOR]

Objective: Identifying potentially modifiable risk factors for ovarian cancer is essential for prevention because this cancer is predominantly detected at a late stage. Here, we estimated the relations of general adiposity and measures reflecting body fat distribution to the risk of epithelial ovarian cancer.Methods: We ascertained 683 ovarian epithelial cancers (343 high-grade serous, 141 non-high grade serous) among 145,575 women, aged 50-72 years (median follow-up 12.6 years), from the National Institutes of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study. Using Cox models, we estimated confounder-adjusted hazard ratios (HRs) and 95% confidence intervals (CI) for associations of overall ovarian cancer, high-grade serous and non-high-grade serous carcinoma with body mass index, waist circumference, hip circumference, waist-hip ratio, waist-height ratio, body adiposity index, body shape index, and abdominal volume index.Results: Anthropometric measures were unrelated to overall ovarian cancer, high-grade serous cancer, and non-high-grade serous cancer. For example, the HR for overall ovarian cancer per standard deviation increment of body mass index at baseline was 0.98 (95% CI 0.88-1.10). Similar associations were observed with measurements of body fat distribution.Conclusion: These results do not indicate that adult adiposity is associated with ovarian cancer risk in post-menopausal women. [ABSTRACT FROM AUTHOR]

Background Fat mass and fat-free mass may play independent roles in mortality risk but available studies on body composition have yielded inconsistent results. Objective The aim was to determine the relations of body fat mass and fat-free mass to risk of mortality. Methods In pooled data from 7 prospective cohorts encompassing 16,155 individuals aged 20 to 93 y (median, 44 y), we used Cox regression and restricted cubic splines to estimate HRs and 95% CIs for the relation of body composition, measured by bioelectrical impedance analysis, to total mortality. We adjusted for age, study, sex, ethnicity, history of diabetes mellitus, education, smoking, physical activity, and alcohol consumption. Results During a median follow-up period of 14 y (range, 3–21 y), 1347 deaths were identified. After mutual adjustment for fat mass and fat-free mass, fat mass showed a J-shaped association with mortality (overall P value < 0.001; P for nonlinearity = 0.003). Using a fat mass index of 7.3 kg/m2 as the reference, a high fat mass index of 13.0 kg/m2 was associated with an HR of 1.56 (95% CI: 1.30, 1.87). In contrast, fat-free mass showed an inverse association with mortality (overall P  value < 0.001; P for nonlinearity = 0.001). Compared with a low fat-free mass index of 16.1 kg/m2, a high fat-free mass of 21.9 kg/m2 was associated with an HR of 0.70 (95% CI: 0.56, 0.87). Conclusions Fat mass and fat-free mass show opposing associations with mortality. Excess fat mass is related to increased mortality risk, whereas fat-free mass protects against risk of mortality. These findings suggest that body composition provides important prognostic information on an individual's mortality risk not provided by traditional proxies of adiposity such as BMI. [ABSTRACT FROM AUTHOR]

Abstract Background Several epidemiologic studies have examined the association between physical activity and pancreatic cancer risk; however, the results of these studies are not consistent. Methods This study examined the associations of total, moderate, and vigorous physical activity to pancreatic cancer in a cohort of 33,530 U.S. women enrolled in the Breast Cancer Detection Demonstration Project (BCDDP). At baseline (1987–1989), information on physical activity over the past year was obtained using a self-administered questionnaire. Cox proportional hazards regression was used to estimate relative risks (RR) and 95% confidence intervals of pancreatic cancer risk. Results 70 incident cases of pancreatic cancer were ascertained during 284,639 person years of follow-up between 1987–1989 and 1995–1998. After adjustment for age, body mass index, smoking status, history of diabetes, and height, increased physical activity was related to a suggestively decreased risk of pancreatic cancer. The RRs for increasing quartiles of total physical activity were 1.0, 0.80, 0.66, 0.52 (95% CI = 0.26, 1.05; ptrend = 0.05). This association was consistent across subgroups defined by body mass index and smoking status. We also observed statistically non-significant reductions in pancreatic cancer risk for women in the highest quartile of moderate (RR = 0.57; 95% CI = 0.26, 1.26) and highest quartile of vigorous physical activity (RR = 0.63; 95% CI = 0.31, 1.28) compared to their least active counterparts. Conclusion Our study provides evidence for a role of physical activity in protecting against pancreatic cancer.

Increased cardiorespiratory fitness is related to decreased risk of major chronic illnesses, including cardiovascular disease, type 2 diabetes, and cancer, but its association with colorectal cancer specifically has received very little attention. We examined the relation of cardiorespiratory fitness to colorectal cancer in 59,191 UK Biobank participants aged 39–70 years without prevalent cancer at baseline, followed from 2009 to 2014. Submaximal bicycle ergometry was conducted at study entry, and cardiorespiratory fitness was defined as physical work capacity at 75% of the maximum heart rate, standardised to body mass (PWC75%). Multivariable Cox proportional hazards regression was performed to obtain hazard ratios (HR) and corresponding 95% confidence intervals (CI). During a mean follow-up of 4.6 years, 232 participants developed colorectal cancer (151 colon cancers; 79 rectal cancers). When comparing the 75th to the 25th percentiles of PWC75%, the multivariable-adjusted HR of colorectal cancer was 0.78 (95% CI 0.62–0.97). That relation was largely driven by an inverse association with colon cancer (HR 0.74, 95% CI 0.56–0.97) and less so with rectal cancer (HR 0.88, 95% CI 0.62–1.26; p value for difference by colorectal cancer endpoint = 0.056). The inverse relation of cardiorespiratory fitness with colorectal cancer was more evident in men (HR 0.72, 95% CI 0.55–0.94) than women (HR 0.99, 95% CI 0.71–1.38), although the gender difference was not statistically significant (p value for interaction = 0.192). Increased cardiorespiratory fitness is associated with decreased risk of colorectal cancer. Potential heterogeneity by colorectal cancer anatomic subsite and gender requires further study. [ABSTRACT FROM AUTHOR]

Effectors from the immune system can modulate the course and possibly the early development of gliomas. We, therefore, hypothesized that autoimmune diseases associated with increased immune‐surveillance may also modulate the risk of human glioma. To test this hypothesis, we used data from the well‐validated Clinical Practice Research Datalink (CPRD) GOLD from the UK to analyze the association of immune‐related disorders or use of immunosuppressive drugs and the risk of glioma. We identified 3112 incident glioma cases diagnosed between 1995 and 2017. We randomly selected up to 10 controls, matching them to glioma cases on age, sex, index date, general practice, and number of years of active history in the database prior to the index date. We performed conditional logistic regression analyses to estimate Odds Ratios (ORs) of glioma among those exposed to allergies, autoimmune diseases, and immunosuppressive drugs. Overall, we found no materially altered association between a history of any autoimmune disease (OR 0.98, 95% CI 0.86‐1.11), allergy (OR 0.97, 95% CI 0.89‐1.05), or use of immunosuppressive drugs and the risk of glioma. However, subgroup analyses among younger patients found a statistically significant increased risk of glioma in patients with a history of inflammatory bowel disease (IBD) (OR 2.59, 95% CI 1.31‐5.12). There was also an inverse association between asthma and risk of glioma in patients with longer survival (OR 0.73, 95% CI 0.58‐0.91) and between long‐term duration diabetes and risk of glioma (OR 0.71, 95% CI 0.53‐0.96). [ABSTRACT FROM AUTHOR]

Background: Previously we showed that adulthood body mass index (BMI) trajectories that result in obesity were associated with elevated risks of fatal prostate cancer (PCA). To further explore this relationship, we conducted a study within the NIH-AARP Diet and Health Study.Methods: Among 153 730 eligible men enrolled in the NIH-AARP cohort from 1995 to 1996 (median follow-up = 15.1 years), we identified 630 fatal PCA cases and 16 896 incident cases. BMI was assessed for ages 18, 35 and 50 and at study entry, enabling examination of latent class-identified BMI trajectories. Hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using Cox proportional hazards regression.Results: BMI at study entry (mean age = 63, HR = 1.12; 95% CI = 1.01, 1.24, per 5-unit increase) and maximum BMI during adulthood (HR = 1.12; 95% CI = 1.02, 1.24, per 5-unit increase) shared modest associations with increased risk of fatal PCA. Smoking status likely modified the relationship between BMI trajectories and fatal PCA (Pinteraction = 0.035 via change-in-estimate variable section, P = 0.065 via full a priori model). Among never-smokers, BMI trajectory of normal weight to obesity was associated with increased risk of fatal disease (HR = 2.37; 95% CI = 1.38, 4.09), compared with the maintained normal weight trajectory, whereas there was no association among former or current-smokers. Total and non-aggressive PCA exhibited modest inverse associations with BMI at all ages, whereas no association was observed for aggressive PCA.Conclusions: Increased BMI was positively associated with fatal PCA, especially among never-smokers. Future studies that examine PCA survival will provide additional insight as to whether these associations are the result of biology or confounding. [ABSTRACT FROM AUTHOR]

High‐grade glioma (HGG) is associated with poor prognosis. Drug repurposing evolves as new modality to improve standard therapy. The antidiabetic drug metformin has been found to inhibit glioma cell growth in vitro and in vivo. The aim of the present retrospective cohort study was to evaluate the survival of patients with HGG with or without treatment with metformin, based on a large cohort of a cancer registry. The analysis included 1,093 patients with HGG diagnosed between 1998 and 2013 from the population‐based clinical cancer registry Regensburg (Germany), which covers 2.1 Mio inhabitants and 98% of all cancer diagnoses. We performed multivariable adjusted Cox‐regression analyses. Hazard Ratios (HRs) with 95% Confidence Intervals (CIs) for overall survival (OS) and progression‐free survival (PFS) of patients with HGG with or without treatment with metformin were obtained. Use of metformin was associated with a significantly better overall and progression‐free survival of patients with WHO grade III glioma (HR for OS = 0.30; 95% CI = 0.11–0.81, HR for PFS = 0.29; 95% CI = 0.11–0.78), while there were no significant relations with OS (HR = 0.83; 95% CI = 0.57–1.20) or PFS (HR = 0.85; 95% CI = 0.59–1.22) in patients with WHO grade IV glioma. In conclusion, use of metformin is associated with better overall and progression‐free survival of patients with WHO grade III. Possible underlying mechanisms include the higher prevalence of IDH mutations in WHO grade III glioma, which might sensitize to the metabolic drug metformin. What's new? The oral diabetes drug metformin seems to boost survival of high grade glioma (HGG). In this study, the authors examined metformin use in a cohort of over 1,000 HGG patients. Patients with WHO grade III glioma had better survival if they were taking metformin, while no improvement in outcomes was associated with other diabetes medications, including sulfonylureas or insulin. No benefit was observed in patients with WHO grade IV cancers. The authors propose that the survival benefit may be linked to IDH mutations, which often occur in stage III but not stage IV gliomas. [ABSTRACT FROM AUTHOR]