Physical work exposure matrix for use in the UK Biobank.

BACKGROUND: UK Biobank (UKB) is a large prospective cohort capturing numerous health outcomes, but limited occupational information (job title, self-reported manual work and occupational walking/standing). AIMS: To create and evaluate validity of a linkage between UKB and a job exposure matrix for physical work exposures based on the US Occupational Information Network (O*NET) database. METHODS: Job titles and UK Standard Occupational Classification (SOC) codes were collected during UKB baseline assessment visits. Using existing crosswalks, UK SOC codes were mapped to US SOC codes allowing linkage to O*NET variables capturing numerous dimensions of physical work. Job titles with the highest O*NET scores were assessed to evaluate face validity. Spearman's correlation coefficients were calculated to compare O*NET scores to self-reported UKB measures. RESULTS: Among 324 114 participants reporting job titles, 323 936 were linked to O*NET. Expected relationships between scores and self-reported measures were observed. For static strength (0-7 scale), the median O*NET score was 1.0 (e.g. audiologists), with a highest score of 4.88 for stone masons and a positive correlation with self-reported heavy manual work (Spearman's coefficient = 0.50). For time spent standing (1-5 scale), the median O*NET score was 2.72 with a highest score of 5 for cooks and a positive correlation with self-reported occupational walking/standing (Spearman's coefficient = 0.56). CONCLUSIONS: While most jobs were not physically demanding, a wide range of physical work values were assigned to a diverse set of jobs. This novel linkage of a job exposure matrix to UKB provides a potentially valuable tool for understanding relationships between occupational exposures and disease.

Body size throughout the life-course and incident benign prostatic hyperplasia-related outcomes and nocturia.

BACKGROUND: Existing evidence suggests that there is an association between body size and prevalent Benign Prostatic Hyperplasia (BPH)-related outcomes and nocturia. However, there is limited evidence on the association between body size throughout the life-course and incident BPH-related outcomes. METHODS: Our study population consisted of men without histories of prostate cancer, BPH-related outcomes, or nocturia in the intervention arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) (n = 4710). Associations for body size in early- (age 20), mid- (age 50) and late-life (age ≥ 55, mean age 60.7 years) and weight change with incident BPH-related outcomes (including self-reported nocturia and physician diagnosis of BPH, digital rectal examination-estimated prostate volume ≥ 30 cc, and prostate-specific antigen [PSA] concentration > 1.4 ng/mL) were examined using Poisson regression with robust variance estimation. RESULTS: Men who were obese in late-life were 25% more likely to report nocturia (Relative Risk (RR): 1.25, 95% Confidence Interval (CI): 1.11-1.40; p-trendfor continuous BMI < 0.0001) and men who were either overweight or obese in late-life were more likely to report a prostate volume ≥ 30 cc (RRoverweight: 1.13, 95% CI 1.07-1.21; RRobese: 1.10, 95% CI 1.02-1.19; p-trendfor continuous BMI = 0.017) as compared to normal weight men. Obesity at ages 20 and 50 was similarly associated with both nocturia and prostate volume ≥ 30 cc. Considering trajectories of body size, men who were normal weight at age 20 and became overweight or obese by later-life had increased risks of nocturia (RRnormal to overweight: 1.09, 95% CI 0.98-1.22; RRnormal to obese: 1.28, 95% CI 1.10-1.47) and a prostate volume ≥ 30 cc (RRnormal to overweight: 1.12, 95% CI 1.05-1.20). Too few men were obese early in life to examine the independent effect of early-life body size. Later-life body size modified the association between physical activity and nocturia. CONCLUSIONS: We found that later-life body size, independent of early-life body size, was associated with adverse BPH outcomes, suggesting that interventions to reduce body size even late in life can potentially reduce the burden of BPH-related outcomes and nocturia.

Influence of built environment on quality of life changes in African-American patients with non-metastatic breast cancer.

Research links the built environment to health outcomes, but little is known about how this affects quality of life (QOL) of African American breast cancer patients, especially those residing in disadvantaged neighborhoods. Using latent trajectory models, we examined whether the built environment using Google Street View was associated with changes in QOL over a 2-year follow-up in 228 newly diagnosed African American breast cancer patients. We measured QOL using the RAND 36-Item Health Survey subscales. After adjusting for covariates, improvement in emotional well-being and pain over time was greater for women living on streets with low-quality (vs. high-quality) sidewalks.

Early major complications after bariatric surgery in the USA, 2003-2014: a systematic review and meta-analysis.

The effectiveness of bariatric surgery has been well-studied. However, complications after bariatric surgery have been understudied. This review assesses <30-d major complications associated with bariatric procedures, including anastomotic leak, myocardial infarction and pulmonary embolism. This review included 71 studies conducted in the USA between 2003 and 2014 and 107,874 patients undergoing either gastric bypass, adjustable gastric banding or sleeve gastrectomy, with mean age of 44 years and pre-surgery body mass index of 46.5 kg m-2 . Less than 30-d anastomotic leak rate was 1.15%; myocardial infarction rate was 0.37%; pulmonary embolism rate was 1.17%. Among all patients, mortality rate following anastomotic leak, myocardial infarction and pulmonary embolism was 0.12%, 0.37% and 0.18%, respectively. Among surgical procedures, <30-d after surgery, sleeve gastrectomy (1.21% [95% confidence interval, 0.23-2.19%]) had higher anastomotic leak rate than gastric bypass (1.14% [95% confidence interval, 0.84-1.43%]); gastric bypass had higher rates of myocardial infarction and pulmonary embolism than adjustable gastric banding or sleeve gastrectomy. During the review, we found that the quality of complication reporting is lower than the reporting of other outcomes. In summary, <30-d rates of the three major complications after either one of the procedures range from 0% to 1.55%. Mortality following these complications ranges from 0% to 0.64%. Future studies reporting complications after bariatric surgery should improve their reporting quality.

Early versus 6-12 week postpartum glucose tolerance testing for women with gestational diabetes.

OBJECTIVE: The objective of this study is to estimate the accuracy of early oral glucose tolerance testing (GTT), to predict impaired glucose tolerance. STUDY DESIGN: This was a prospective cohort study. Women received an early 75 g 2 h GTT between postpartum days 2-4 and again 6-12 weeks postpartum. The ability of the early GTT to accurately detect impaired glucose tolerance and diabetes was assessed by calculating sensitivity, specificity, positive predictive value (PPV) and negative predictive values (NPVs). The routine 6-12-week postpartum GTT was considered the gold standard. RESULTS: The early GTT was completed by 100% of subjects, whereas only 31 of 58 (53%) women returned to complete the 6-12-week postpartum GTT. The early GTT had modest sensitivity for impaired glucose tolerance (62.5%) and overt diabetes (50%). However, it had excellent specificity (100%), PPV (100%) and NPV (96.7%) for diabetes. The NPV for impaired glucose tolerance with the early GTT was 80%. CONCLUSION: Rates of 6-12 week postpartum GTT completion among patients with gestational diabetes is poor. Appropriate postpartum management may improve by using the early GTT as a screening test.

Breastfeeding and breast cancer risk by receptor status--a systematic review and meta-analysis.

BACKGROUND: Breastfeeding is inversely associated with overall risk of breast cancer. This association may differ in breast cancer subtypes defined by receptor status, as they may reflect different mechanisms of carcinogenesis. We conducted a systematic review and meta-analysis of case-control and prospective cohort studies to investigate the association between breastfeeding and breast cancer by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status. DESIGN: We searched the PubMed and Scopus databases and bibliographies of pertinent articles to identify relevant articles and used random-effects models to calculate summary odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: This meta-analysis represents 27 distinct studies (8 cohort and 19 case-control), with a total of 36 881 breast cancer cases. Among parous women, the risk estimates for the association between ever (versus never) breastfeeding and the breast cancers negative for both ER and PR were similar in three cohort and three case-control studies when results were adjusted for several factors, including the number of full-term pregnancies (combined OR 0.90; 95% CI 0.82-0.99), with little heterogeneity and no indication of publication bias. In a subset of three adjusted studies that included ER, PR, and HER2 status, ever breastfeeding showed a stronger inverse association with triple-negative breast cancer (OR 0.78; 95% CI 0.66-0.91) among parous women. Overall, cohort studies showed no significant association between breastfeeding and ER+/PR+ or ER+ and/or PR+ breast cancers, although one and two studies (out of four and seven studies, respectively) showed an inverse association. CONCLUSIONS: This meta-analysis showed a protective effect of ever breastfeeding against hormone receptor-negative breast cancers, which are more common in younger women and generally have a poorer prognosis than other subtypes of breast cancer. The association between breastfeeding and receptor-positive breast cancers needs more investigation.

High-dose therapy and autologous stem cell transplant in older adults with multiple myeloma.

Randomized trials showing that high-dose therapy with autologous stem cell transplant (ASCT) improved the overall survival (OS) in multiple myeloma (MM) excluded patients over age 65. To compare the outcomes of older adults with MM who underwent ASCT with non-transplant strategies, we identified 146 patients aged 65-77 with newly diagnosed MM seen in the Washington University School of Medicine from 2000 to 2010. Survival among patients who did (N=62) versus did not (N=84) undergo ASCT was compared using Cox proportional hazards modeling, controlling for comorbidities, Eastern Cooperative Oncology Group performance status (PS) and the propensity to undergo ASCT. Median age was 68 years (range 65-77). PS and comorbidities did not differ significantly between those who did versus those who did not undergo ASCT. Median OS was significantly longer in patients who underwent ASCT than in those who did not (median 56.0 months (95% confidence intervals (CIs) 49.1-65.4) versus 33.1 months (24.3-43.1), P=0.004). Adjusting for PS, comorbidities, Durie-Salmon stage and the propensity to undergo ASCT, ASCT was associated with superior OS (HR for mortality 0.52 (95% CI 0.30-0.91), P=0.02). In a cohort of older adults with MM, undergoing ASCT was associated with a nearly 50% lower mortality, after controlling for PS, comorbidities, stage and the propensity to undergo ASCT.

Comparative effectiveness on survival of zoledronic acid versus pamidronate in multiple myeloma.

Zoledronic acid and pamidronate are the two bisphosphonates approved in the United States to reduce multiple myeloma skeletal complications. Little prior evidence exists comparing survival outcomes between the two. We evaluated the incidence of skeletal-related events and overall survival in patients with myeloma treated with zoledronic acid versus pamidronate using a cohort of 1018 United States veterans. At a median follow-up of 26.9 months, patients receiving zoledronic acid had a 22% reduction in risk of death compared to pamidronate (hazard ratio 0.78; 95% confidence interval, 0.67-0.92). The benefit persisted after controlling for potential confounders. Adjusted Cox modeling with inverse probability weighting and propensity score matching supported these findings. Zoledronic acid was also associated with a 25% decrease in skeletal-related events. Zoledronic acid is associated with increased overall survival and decreased skeletal-related events compared to pamidronate in patients with multiple myeloma and should become the preferred bisphosphonate.

Diabetes and pancreatic cancer survival: a prospective cohort-based study.

BACKGROUND: Diabetes is a risk factor for pancreatic cancer but its association with survival from pancreatic cancer is poorly understood. Our objective was to investigate the association of diabetes with survival among pancreatic cancer patients in a prospective cohort-based study where diabetes history was ascertained before pancreatic cancer diagnosis. METHODS: We evaluated survival by baseline (1993-2001) self-reported diabetes history (n=62) among 504 participants that developed exocrine pancreatic cancer within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality were estimated using Cox proportional hazards model, adjusted for age, sex, body mass index, race, smoking, and tumour stage (local, locally advanced, and metastatic). RESULTS: The multivariable-adjusted HR for mortality comparing participants with diabetes to those without was 1.52 (95% CI=1.14-2.04, P-value <0.01). After excluding those diagnosed with pancreatic cancer within 3 years of study enrolment, HR for mortality among those with diabetes was 1.45 (95% CI=1.06-2.00, P-value=0.02). CONCLUSIONS: Using prospectively collected data, our findings indicate that diabetes is associated with worse survival among patients with pancreatic cancer.

Gastric Malignancy Survival in Zambia, Southern Africa: A Two Year Follow up Study.

Background: Gastric cancer poses a significant global health burden. It is the second most common cause of cancer death worldwide and the ninth leading cause of cancer mortality in Zambia, at a rate of 3.8/100,000; comparable to USA (2/100,000) and UK (3.4/100,000). Survival data on gastric malignancy in Zambia is not known. Objectives: To provide preliminary survival rates of patients with histologically proven gastric adenocarcinoma in Zambia. Study Design: Using our prospective gastric cancer research database, we conducted a retrospective audit of patients diagnosed with gastric cancer at the University Teaching Hospital, Zambia, from June 2010 until January 2012. We contacted patients or their relatives using phone numbers provided at time of enrollment. Main Outcomes: We reviewed age, sex, demographic data (income, education), body mass index, symptoms, duration of symptoms, treatment (surgery, chemotherapy, radiotherapy or combination) and survival outcome. Analysis was performed using Kaplan-Meier models and log rank test. Results: Fifty one patients were diagnosed with gastric adenocarcinoma during the study period, but follow-up data were available for 50. Median survival was 142 days. Age, sex, income, education, BMI, tumor location, and treatment modality were not significantly associated with overall survival. In Cox regression models, covariates associated with survival were a history of regular alcohol intake (HR 0.49, 95%CI 0.26,0.92; P=0.025) and intestinal type cancer histology (HR 0.40, 95%CI 0.19,0.83; P=0.01). Conclusion: Prognosis of newly diagnosed gastric cancer in Zambia is poor with significant mortality within 1 year of diagnosis, particularly among patients with weight loss and dysphagia.

Validation of Rosner-Colditz breast cancer incidence model using an independent data set, the California Teachers Study.

To validate an established breast cancer incidence model in an independent prospective data set. After aligning time periods for follow-up, we restricted populations to comparable age ranges (47-74 years), and followed them for incident invasive breast cancer (follow-up 1994-2008, Nurses' Health Study [NHS]; and 1995-2009, California Teachers Study [CTS]). We identified 2026 cases during 540,617 person years of follow-up in NHS, and 1,400 cases during 288,111 person years in CTS. We fit the Rosner-Colditz log-incidence model and the Gail model using baseline data. We imputed future use of hormones based on type and prior duration of use and other covariates. We assessed performance using area under the curve (AUC) and calibration methods. Participants in the CTS had fewer children, were leaner, consumed more alcohol, and were more frequent users of postmenopausal hormones. Incidence rate ratios for breast cancer showed significantly higher breast cancer in the CTS (IRR = 1.32, 95 % CI 1.24-1.42). Parameters for the log-incidence model were comparable across the two cohorts. Overall, the NHS model performed equally well when applied in the CTS. In the NHS the AUC was 0.60 (s.e. 0.006) and applying the NHS betas to the CTS the performance in the independent data set (validation) was 0.586 (s.e. 0.009). The Gail model gave values of 0.547 (s.e. 0.008), a significant 4 % lower, p < 0.0001. For women 47-69 the AUC values for the log-incidence model are 0.608 in NHS and 0.609 in CTS; and for Gail are 0.569 and 0.572. In both cohorts, performance of both models dropped off in older women 70-87, and later in follow-up (6-12 years). Calibration showed good estimation against SEER with a non-significant 4 % underestimate of overall breast cancer incidence when applying the model in the CTS population (p = 0.098). The Rosner-Colditz model performs consistently well when applied in an independent data set. Performance is stronger predicting incidence among women 47-69 and over a 5-year time interval. AUC values exceed those for Gail by 3-5 % based on AUC when both are applied to the independent validation data set. Models may be further improved with addition of breast density or other markers of risk beyond the current model.

Physical activity and risk of colon adenoma: a meta-analysis.

BACKGROUND: Little evidence is available on the relation of physical activity with colon adenomas, a colon cancer precursor. METHODS: We conducted a systematic literature review and meta-analysis of published studies (in English) through April 2010, examining physical activity or exercise and risk or prevalence of colon adenoma or polyp. Random effects models were used to estimate relative risks (RRs) and corresponding confidence intervals (CIs). A total of 20 studies were identified that examined the association and provided RRs and corresponding 95% CIs. RESULTS: A significant inverse association between physical activity and colon adenomas was found with an overall RR of 0.84 (CI: 0.77-0.92). The association was similar in men (RR=0.81, CI: 0.67-0.98) and women (RR=0.87, CI: 0.74-1.02). The association appeared slightly stronger in large/advanced polyps (RR=0.70, CI: 0.56-0.88). CONCLUSION: This study confirms previous reports of a significant inverse association of physical activity and colon adenoma, and suggests that physical activity can have an important role in colon cancer prevention.

Physical activity and colon cancer prevention: a meta-analysis.

Although an inverse association between physical activity and risk of colon cancer is well established, a formal estimate of the magnitude of this risk reduction that includes recent studies is not available. This analysis examines the association by sex and study design, restricting analyses to studies where data for colon cancer alone were available. The authors reviewed published studies through June 2008 examining the association between physical activity and risk of colon cancer. Heterogeneity and publication bias were evaluated and random effects models used to estimate relative risks (RR). Differences by sex and study design were evaluated. A total of 52 studies were included. An inverse association between physical activity and colon cancer was found with an overall relative risk (RR) of 0.76 (95% confidence interval (CI): 0.72, 0.81). For men, the RR was 0.76 (95% CI: 0.71, 0.82); for women, this was little different, (RR=0.79, 95% CI: 0.71, 0.88). The findings from case-control studies were stronger (RR=0.69, 95% CI: 0.65, 0.74) than for cohort studies (RR=0.83, 95% CI: 0.78, 0.88). This study confirms previous studies reporting an inverse association between physical activity and colon cancer in both men and women, and provides quantitative estimates of the inverse association.

Can weight loss prevent cancer?

We review and update evidence on obesity, weight gain and weight loss in relation to leading cancers since the International Agency for Research on Cancer report of 2002. Emphasis is placed on the time course of disease and implications for weight control to prevent cancer. We conclude that weight loss could prevent a major portion of common cancers.

Comparison of aspects of smoking among the four histological types of lung cancer.

BACKGROUND: The magnitude of the link between cigarette smoking and lung cancer may vary by histological type. METHODS: We used polytomous logistic regression to evaluate whether aspects of smoking have different effects across four histological types in the Nurses' Health Study. RESULTS: From 1976 to 2002, we identified 1062 cases of lung cancer: squamous cell (n = 201), small cell (n = 236), adenocarcinoma (n = 543) and large cell carcinoma (n = 82), among 65 560 current or former smokers. Risk reduction after quitting ranged from an 8% reduction (relative risk (RR): 0.92, 95% CI 0.91 to 0.94) to a 17% reduction (RR: 0.83, 95% CI 0.80 to 0.86) per year for adenocarcinoma and small cell carcinoma, respectively, with a 9% reduction observed for large cell carcinoma and an 11% reduction observed for squamous cell carcinoma. The association of age at smoking initiation and former cigarette smoking was similar across types, while the association of smoking duration differed. The risk of adenocarcinoma increased by 6% per year of smoking, compared to 7% for large cell, 10% for squamous cell and 12% for small cell. The 6% difference between adenocarcinoma and small cell carcinoma is equivalent to a 3.2 to 9.7-fold increase in risk for 20 years of smoking. CONCLUSIONS: The effects of the number of cigarettes smoked per day and years since quitting smoking are different across the major types of lung cancer, which are fully appreciated at long durations of smoking and smoking cessation. Smoking prevention and cessation should continue to be the focus of public health efforts to reduce lung cancer incidence and mortality.

Aspirin and lung cancer risk in a cohort study of women: dosage, duration and latency.

Aspirin may reduce the risk of cancer at some sites but its effect at the lung is unclear. We prospectively examined associations between aspirin use and risk of lung cancer in 109,348 women in the Nurses' Health study from 1980 to 2004. During this time, 1,360 lung cancers were documented in participants 36-82 years of age. Aspirin use and smoking were assessed every 2 years. Risk of lung cancer was a non-significant 16% lower for regular aspirin users of one or two tablets per week and a significant 55% higher for users of 15 or more tablets per week compared with women who never regularly used aspirin. Results were similar when limited to never smokers. For both the low and high quantity aspirin users, risk of lung cancer did not decline or increase with longer durations of use, and associations attenuated as the latency period between aspirin assessment and lung cancer diagnosis was lengthened. Our findings, together with those from previous clinical trials and prospective studies, do not provide consistent evidence that aspirin influences the development of lung cancer and further investigation is required with adjustment for smoking.

A prospective study of postmenopausal hormone use and ovarian cancer risk.

The relationship between postmenopausal hormone use (PMH) and ovarian cancer risk is unclear, particularly for specific hormone formulations, but recent studies suggest that there is a positive association. We conducted a prospective observational study with 82,905 postmenopausal women, including 389 ovarian cancers, in the Nurses' Health Study from 1976 to 2002. Compared with never users of PMH, both current and past users of > or =5 years had a significantly elevated risk of ovarian cancer (RR=1.41, 95% confidence interval (CI) 1.07-1.86 and relative risk (RR)=1.52, 95% CI 1.01-2.27, respectively). Examined by hormone type in continuous years, use of unopposed estrogen was associated with a significant increase in the risk of epithelial ovarian cancer (P for trend <0.001; RR for 5-year increment of use=1.25, 95% CI 1.12-1.38). Use of estrogen plus progestin (RR for 5-year increment of use=1.04, 95% CI 0.82-1.32) was not significantly associated with ovarian cancer risk. Generally, results were similar for serous tumours (RR for 5-year increment of unopposed estrogen use=1.23, 95% CI 1.07-1.40) and slightly stronger for endometrioid tumours (RR for 5-year increment of unopposed estrogen use=1.53, 95% CI 1.20-1.94). Recency of use was not significantly associated with ovarian cancer risk, but statistical power was limited here.

Cyclin D1 A870G polymorphism and the risk of colorectal cancer and adenoma.

Cyclin D1 (CCND1) plays a key role in cell cycle control, particularly in the transition from G1 to S phase, which is regulated by cyclin-dependent kinases. A common adenine to guanine polymorphism (A870G) in the CCND1 gene has been associated with a longer-life protein and an increased risk of colorectal cancer and adenoma in some studies. Among subjects with hereditary nonpolyposis colorectal cancer, the A870G polymorphism has also been associated with a younger age of onset of colorectal cancer. We analysed 181 colorectal cancer cases and 475 matched controls and 524 adenoma cases and 517 matched controls within women in the Nurses' Health Study (NHS) cohort, 171 colorectal cancer cases and 347 matched controls and 372 adenoma cases and 712 matched controls nested within men in the Health Professionals' Follow-Up Study (HPFS) cohort, and 258 colorectal cancer cases and 415 matched controls within men in the Physicians' Health Study (PHS) cohort to assess the risk associated with the CCND1 A870G genotype. Moreover, we assessed whether CCND1 genotype modified the effect of a sporadic (nonsyndromic) family history of colorectal cancer as well as the effect of other dietary and lifestyle risk factors for colorectal cancer and adenoma. In all cohorts combined, the CCND1 polymorphism did not show statistically significant associations to risk of colorectal cancer (odds ratio (OR) for A allele carriers, 1.04; 95% confidence interval (95% CI), 0.82-1.32) or adenoma (OR, 0.96; 95% CI, 0.79-1.18). The CCND1 A870G genotype was associated with a modest, although nonsignificantly elevated risk of colorectal cancer (OR, 1.59; 95% CI, 0.98-2.57) in women. In contrast, the polymorphism was not associated with increased risk of adenoma in either men or women. Among participants with the A870G genotype, a family history of colorectal cancer conferred a substantially greater risk of colorectal cancer in the women (P for interaction=0.06) and adenoma in the men (P for interaction=0.02). Current postmenopausal hormone (PMH) use was associated with a significant reduction in the risk of colorectal cancer and adenoma among women with the A870G genotype, whereas there was no effect of PMH use among those with the GG genotype. The CCND1 polymorphism appeared to confer a modest elevation in the risk of colorectal cancer among women. Moreover, the A870G genotype may enhance the protective effect of postmenopausal oestrogen use on the development of colorectal neoplasia.