What can be learnt from models of incidence rates?

Models of breast cancer incidence have evolved from the observation by Armitage and Doll in the 1950s that the pattern of incidence by age differs for reproductive cancers from those of other major malignancies. Both two-stage and multistage models have been applied to breast cancer incidence. Consistent across modeling approaches, risk accumulation or the rate of increase in breast cancer incidence is most rapid from menarche to first birth. Models that account for the change in risk after menopause and the temporal sequence of reproductive events summarize risk efficiently and give added insights to potentially important mechanistic features. First pregnancy has an adverse impact on progesterone receptor negative tumors, while increasing parity reduces the risk of estrogen/progesterone receptor positive tumors but not estrogen/progesterone receptor negative tumors. Integrated prediction models that incorporate prediction of carrier status for highly penetrant genes and also account for lifestyle factors, mammographic density, and endogenous hormone levels remain to be efficiently implemented. Models that both inform and reflect the emerging understanding of the molecular and cell biology of carcinogenesis are still a long way off

Food Predictors of Plasma Carotenoids

Empirical prediction models that weight food frequency questionnaire (FFQ) food items by their relation to nutrient biomarker concentrations may estimate nutrient exposure better than nutrient intakes derived from food composition databases. Carotenoids may especially benefit because contributing foods vary in bioavailability and assessment validity. Our objective was to develop empirical prediction models for the major plasma carotenoids and total carotenoids and evaluate their validity compared with dietary intakes calculated from standard food composition tables. 4180 nonsmoking women in the Nurses’ Health Study (NHS) blood subcohort with previously measured plasma carotenoids were randomly divided into training (n = 2787) and testing (n = 1393) subsets. Empirical prediction models were developed in the training subset by stepwise selection from foods contributing ≥0.5% to intake of the relevant carotenoid. Spearman correlations between predicted and measured plasma concentrations were compared to Spearman correlations between dietary intake and measured plasma concentrations for each carotenoid. Three to 12 foods were selected for the α-carotene, β-carotene, β-cryptoxanthin, lutein/zeaxanthin, lycopene, and total carotenoids prediction models. In the testing subset, Spearman correlations with measured plasma concentrations for the calculated dietary intakes and predicted plasma concentrations, respectively, were 0.31 and 0.37 for α-carotene, 0.29 and 0.31 for β-carotene, 0.36 and 0.41 for β-cryptoxanthin, 0.28 and 0.31 for lutein/zeaxanthin, 0.22 and 0.23 for lycopene, and 0.22 and 0.27 for total carotenoids. Empirical prediction models may modestly improve assessment of some carotenoids, particularly α-carotene and β-cryptoxanthin

Effects of reproductive and demographic changes on breast cancer incidence in China: A modeling analysis

Background: Breast cancer incidence is currently low in China. However, the distribution of reproductive and lifestyle risk factors for breast cancer among Chinese women is changing rapidly. We quantified the expected effect of changes in breast cancer risk factors on future rates of breast cancer in China. Methods: We first validated and calibrated the Rosner-Colditz log-incidence breast cancer model in Chinese women who participated in the Shanghai Women's Health Study cohort (N = 74 942). We then applied the calibrated model to a representative sample of Chinese women who were aged 35-49 years in 2001 using data from the Chinese National Family Planning and Reproductive Health Survey (NFPRHS, N = 17 078) to predict the age-specific and cumulative breast cancer incidence among all Chinese women of this age group. We evaluated the relative impact of changes in modifiable risk factors, including alcohol intake, parity, postmenopausal hormone use, and adult weight gain, on cumulative incidence of breast cancer. Results: Breast cancer incidence in China is expected to increase substantially from current rates, estimated at 10-60 cases per 100 000 women, to more than 100 new cases per 100 000 women aged 55-69 years by 2021. We predicted 2.5 million cases of breast cancer by 2021 among Chinese women who were 35-49 years old in 2001. Modest reductions in hormone and alcohol use, and weight maintenance could prevent 270 000 of these cases. Conclusions: China is on the cusp of a breast cancer epidemic. Although some risk factors associated with economic development are largely unavoidable, the substantial predicted increase in new cases of breast cancer calls for urgent incorporation of this disease in future health care infrastructure planning

Surrogates of Long-Term Vitamin D Exposure and Ovarian Cancer Risk in Two Prospective Cohort Studies

Experimental evidence and ecologic studies suggest a protective role of vitamin D in ovarian carcinogenesis. However, epidemiologic studies using individual level data have been inconsistent. We evaluated ultraviolet (UV)-B radiation, vitamin D intake, and predicted plasma 25-hydroxyvitamin D [25(OH)D] levels as long-term surrogates of vitamin D exposure within the Nurses’ Health Study (NHS) and NHSII. We estimated incidence rate ratios (RRs) and 95% confidence intervals (CIs) for risk of overall ovarian cancer and by histologic subtype using Cox proportional hazards models. Between 1976 and 2010 in NHS and 1989 and 2011 in NHSII, we identified a total of 1,225 incident epithelial ovarian cancer cases (NHS: 970, NHSII: 255) over 4,628,648 person-years of follow-up. Cumulative average UV-B exposure was not associated with ovarian cancer risk in NHS (Ptrend = 0.08), but was associated with reduced risk in NHSII (highest vs. lowest category RR = 0.67; 95% CI: 0.50, 0.89; Ptrend < 0.01). When stratified by histologic subtype, UV-B flux was positively associated with risk of serous tumors in NHS (Ptrend < 0.01), but inversely associated in NHSII (Ptrend = 0.01). Adjusted for confounders, ovarian cancer risk was not associated with vitamin D intake from food or supplements or with predicted 25(OH)D levels. Our study does not strongly support a protective role for vitamin D in ovarian cancer risk

Prospective Study of Bowel Movement, Laxative Use, and Risk of Colorectal Cancer among Women

The authors prospectively examined the association between bowel movement frequency, laxative use, and the risk of colorectal cancer in 84, 577 women of the Nurses' Health Study living in the United States, 36-61 years of age and free of cancer in 1982. Between 1984 and 1996, 611 incident cases of colorectal cancer were documented. After controlling for age, body mass index, fiber intake, postmenopausal status and hormone use, physical activity, and use of laxatives, the relative risks associated with having bowel movements every third day or less, compared with those with bowel movements once daily, were 0.94 (95% confidence interval (Cl): 0.69, 1.28) for colorectal cancer, 0.88 (95% Cl: 0.62, 1.26) for colon cancer, and 1.18 (95% Cl: 0.63, 2.20) for rectal cancer. Compared with women who never used laxatives, the multivariate relative risks associated with weekly to daily laxative use were 1.00 (95% Cl: 0.72, 1.40) for colorectal cancer, 1.09 (95% Cl: 0.76, 1.57) for colon cancer, and 0.68 (95% Cl: 0.29, 1.57) for rectal cancer. These findings do not support an association between infrequent bowel movement, laxative use, and risk of colorectal cancer and indicate that simple questions directed at bowel movement frequency are unlikely to enhance our ability to predict colorectal cancer risk. Am J Epidemiol2000; 151: 958-6

Associations of aspirin and other anti-inflammatory medications with breast cancer risk by the status of COX-2 expression

BACKGROUND: We investigated the associations of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) with breast cancer risk by the status of COX-2 protein expression. METHODS: This study included 421 cases and 3,166 controls from a nested case-control study within the Nurses\u27 Health Study (NHS) and Nurses\u27 Health Study II (NHSII) cohorts. Information on medication use was first collected in 1980 (NHS) and 1989 (NHSII) and was updated biennially. Medication use was defined as none, past or current; average cumulative dose and frequency were calculated for all past or current users using data collected from all biannual questionnaires preceding the reference date. Immunochemistry for COX-2 expression was performed using commercial antibody (Cayman Chemical and Thermo Fisher Scientific). We used polychotomous logistic regression to quantify associations of aspirin and NSAIDs with the risk of COX2+ and COX2- breast cancer tumors, while adjusting for known breast cancer risk factors. All tests of statistical significance were two-sided. RESULTS: In multivariate analysis, we found no differences in associations of the aspirin exposures and NSAIDs with breast cancer risk by COX2 expression status. In stratified analyses by COX2 status, significant associations of these medications with breast cancer risk were observed for dosage of aspirin among current users in COX2- tumors (OR for \u3e 5 tablets per week vs. none 1.71, 95% CI 1.01-2.88, p-trend 0.04). Regular aspirin use was marginally associated with the risk of COX2- tumors (p-trend = 0.06). CONCLUSIONS: Our findings suggested no differences in associations of aspirin and other NSAIDs with COX2+ and COX2- tumors

Recruitment and retention of participants in a pragmatic randomized intervention trial at three community health clinics: Results and lessons learned

Background: Obesity and hypertension and their associated health complications disproportionately affect communities of color and people of lower socioeconomic status. Recruitment and retention of these populations in research trials, and retention in weight loss trials has been an ongoing challenge. Methods: Be Fit, Be Well was a pragmatic randomized weight loss and hypertension management trial of patients attending one of three community health centers in Boston, Massachusetts. Participants were asked to complete follow-up assessments every 6-months for two years. We describe challenges encountered and strategies implemented to recruit and retain trial participants over the 24-month intervention. We also identify baseline participant characteristics associated with retention status. Retention strategies included financial incentives, contact between assessment visits, building relationships with health center primary care providers (PCPs) and staff, and putting participant convenience first. Results: Active refusal rates were low with 130 of 2,631 patients refusing participation (4.9%). Of 474 eligible persons completing telephone screening, 365 (77.0%) completed their baseline visit and were randomized into the study. The study population was predominantly non-Hispanic Black (71.2%), female (68.5%) and reported annual household income of less than $35,000 (70.1%). Recruitment strategies included use of passive approval of potential participants by PCPs, use of part-time staff, and outsourcing calls to a call center. A total of 314 (86.0%) people completed the 24-month visit. Retention levels varied across study visits and intervention condition. Most participants completed three or more visits (69.6%), with 205 (56.2%) completing all four. At 24-months, lower retention was observed for males and the intervention condition. Retention strategies included building strong relationships with clinic staff, flexibility in overcoming participant barriers through use of taxi vouchers, night and weekend appointments, and keeping participants engaged via newsletters and social gatherings. Conclusion: We were able to retain 86.0% of participants at 24-months. Recruitment and retention of high percentages of racial/ethnic minorities and lower income samples is possible with planning, coordination with a trusted community setting and staff (e.g. community health centers and RAs), adaptability and building strong relationships. Trial registration Clinicaltrials.gov Identifier: NCT0066181

Lung Cancer and Vehicle Exhaust in Trucking Industry Workers

Background: An elevated risk of lung cancer in truck drivers has been attributed to diesel exhaust exposure. Interpretation of these studies specifically implicating diesel exhaust as a carcinogen has been limited because of limited exposure measurements and lack of work records relating job title to exposure-related job duties. Objectives: We established a large retrospective cohort of trucking company workers to assess the association of lung cancer mortality and measures of vehicle exhaust exposure.Methods Work records were obtained for 31,135 male workers employed in the unionized U.S. trucking industry in 1985. We assessed lung cancer mortality through 2000 using the National Death Index, and we used an industrial hygiene review and current exposure measurements to identify jobs associated with current and historical use of diesel-, gas-, and propane-powered vehicles. We indirectly adjusted for cigarette smoking based on an industry survey.Results Adjusting for age and a healthy-worker survivor effect, lung cancer hazard ratios were elevated in workers with jobs associated with regular exposure to vehicle exhaust. Mortality risk increased linearly with years of employment and was similar across job categories despite different current and historical patterns of exhaust-related particulate matter from diesel trucks, city and highway traffic, and loading dock operations. Smoking behavior did not explain variations in lung cancer risk. Conclusions: Trucking industry workers who have had regular exposure to vehicle exhaust from diesel and other types of vehicles on highways, city streets, and loading docks have an elevated risk of lung cancer with increasing years of work.Statistic

A prospective cohort study of dietary indices and incidence of epithelial ovarian cancer

Background: Several dietary indices have been developed to measure overall diet quality, including the Healthy Eating Index-2005 (HEI-2005), which measures adherence to the 2005 Dietary Guidelines from the USDA; the Alternative Healthy Eating Index-2010 (AHEI-2010), which is based on foods and nutrients predictive of chronic disease risk; and the Alternate Mediterranean Diet Score (aMDS), which is an index that characterizes traditional food patterns of Mediterranean countries. Few studies have evaluated diet quality and ovarian cancer risk. Methods: We assessed the associations of the HEI-2005, AHEI-2010, and aMDS with risk of epithelial ovarian cancer prospectively among women in the Nurses’ Health Study. We used Cox proportional hazards models, adjusting for known ovarian cancer risk factors. Results: During 24 years of follow-up, we documented 696 incident epithelial ovarian cancer cases among 82,948 women with diet information. The multivariate adjusted hazard ratios (95% confidence interval; Ptrend) of epithelial ovarian cancer comparing the highest with the lowest quintile were 1.03 (0.80-1.34; 0.77) for the AHEI-2010, 0.85 (0.65-1.12; 0.57) for the HEI-2005, and 0.91 (0.71-1.18; 0.44) for the aMDS. Conclusions: We did not observe any clear association of three diet quality scores with ovarian cancer risk. Further work should other metrics of evaluating diet quality that may be more relevant cancer risk. Electronic supplementary material The online version of this article (doi:10.1186/s13048-014-0112-4) contains supplementary material, which is available to authorized users