Low serum cholesterol as a risk factor for kidney and bladder cancer among Korean men: using a national cohort sample

US urban–rural disparities in breast cancer-screening practices at the national, regional, and state level, 2012–2016 Abstract Purpose Previous studies suggesting that rural US women may be less likely to have a recent mammogram than urban women are limited in either scope or granularity. This study explored urban–rural disparities in US breast cancer-screening practices at the national, regional, and state levels. Methods We used data from the 2012, 2014, and 2016 Behavioral Risk Factor Surveillance Systems surveys. Logistic models were utilized to examine the impact of living in an urban/rural area on mammogram screening at three geographic levels while adjusting for covariates. We then calculated average adjusted predictions (AAPs) and average marginal effects (AMEs) to isolate the association between breast cancer screening and the urban/rural factor. Results At all geographic levels, AAPs of breast cancer screening were similar among urban, suburban, and rural residents. Regarding “ever having a mammogram” and “having a recent mammogram,” urban women had small but significantly higher adjusted probabilities (AAP: 94.6%, 81.1%) compared to rural women (AAP: 93.5%, 80.2%). Conclusions While urban–rural differences in breast cancer screening are small, they can translate into tens of thousands of rural women not receiving mammograms. Hence, there is a need to continue screening initiatives in these areas to reduce the number of breast cancer deaths.

Substitution of dietary protein sources in relation to colorectal cancer risk in the NIH-AARP cohort study Abstract Purpose To evaluate the substitution effect of plant for animal protein with risk of CRC in the large prospective National Institutes of Health-AARP cohort study. Methods Protein intake was assessed at baseline using a food frequency questionnaire. HRs and 95% CIs were estimated using multivariable adjusted hazard ratios from Cox proportional hazards models. We used a substitution model with total protein intake held constant, so that an increase in plant protein was offset by an equal decrease in animal protein. Results Among 489,625 individuals, we identified 8,995 incident CRCs after a median follow-up of 15.5 years. Substituting plant protein for animal protein was associated with a reduced risk of CRC (HR for highest vs. lowest fifth 0.91; 95% CI 0.83–0.99). This reduction in CRC risk appeared to be primarily due to substituting plant protein for red meat protein (HR 0.89; 95% CI 0.81–0.97), not white meat protein (HR 0.96; 95% CI 0.88–1.05) or other animal protein (HR 0.94; 95% CI 0.86–1.03). When further evaluated by source, reduction in CRC risk was limited to the substitution of protein from bread, cereal, and pasta for red meat protein (HR 0.86; 95% CI 0.80–0.93); this association was stronger for distal colon (HR 0.78; 95% CI 0.67–0.90) and rectal cancer (HR 0.79; 95% CI 0.68–0.91) but null for proximal colon (HR 0.99; 95% CI 0.88–1.11). Conclusions This study shows that substituting plant protein for animal protein, especially red meat protein, is associated with a reduced risk of CRC, and suggests that protein source impacts CRC risk.

Leveraging the strength of comprehensive cancer control coalitions to support policy, systems, and environmental change Abstract Strategies that facilitate change to policy, systems, and environmental (PSE) changes can enable behaviors and practices that lead to cancer risk reduction, early detection, treatment access, and improved quality of life among survivors. Comprehensive cancer control is a coordinated collaborative approach to reduce cancer burden and operationalizes PSE change strategies for this purpose. Efforts to support these actions occur at the national, state, and local levels. Resources integral to bolstering strategies for sustainable cancer control include coordination and support from national organizations committed to addressing the burden of cancer, strong partnerships at the state and local levels, funding and resources, an evidence-based framework and program guidance, and technical assistance and training opportunities to build capacity. The purpose of this paper is to describe the impact of public policy, public health programming, and technical assistance and training on the use of PSE change interventions in cancer control. It also describes the foundations for and examples of successes achieved by comprehensive cancer control programs and coalitions using PSE strategies.

Improving the diagnostic accuracy of a stratified screening strategy by identifying the optimal risk cutoff Abstract Background The American Cancer Society (ACS) suggests using a stratified strategy for breast cancer screening. The strategy includes assessing risk of breast cancer, screening women at high risk with both MRI and mammography, and screening women at low risk with mammography alone. The ACS chose their cutoff for high risk using expert consensus. Methods We propose instead an analytic approach that maximizes the diagnostic accuracy (AUC/ROC) of a risk-based stratified screening strategy in a population. The inputs are the joint distribution of screening test scores, and the odds of disease, for the given risk score. Using the approach for breast cancer screening, we estimated the optimal risk cutoff for two different risk models: the Breast Cancer Screening Consortium (BCSC) model and a hypothetical model with much better discriminatory accuracy. Data on mammography and MRI test score distributions were drawn from the Magnetic Resonance Imaging Screening Study Group. Results A risk model with an excellent discriminatory accuracy (c-statistic \(= 0.947\) ) yielded a reasonable cutoff where only about 20% of women had dual screening. However, the BCSC risk model (c-statistic \(= 0.631\) ) lacked the discriminatory accuracy to differentiate between women who needed dual screening, and women who needed only mammography. Conclusion Our research provides a general approach to optimize the diagnostic accuracy of a stratified screening strategy in a population, and to assess whether risk models are sufficiently accurate to guide stratified screening. For breast cancer, most risk models lack enough discriminatory accuracy to make stratified screening a reasonable recommendation.

Inflammation and breast density among female Chinese immigrants: exploring variations across neighborhoods Abstract Purpose We examined associations of inflammation with breast density, a marker of breast cancer risk, among female Chinese immigrants and explored whether associations varied by neighborhood environment. Methods Assessments of serum C-reactive protein (CRP), soluble tumor necrosis factor receptor 2 (sTNFR2), and breast density were performed among 401 Chinese immigrants across the Philadelphia region. Participant addresses were geocoded, with the majority residing in areas representing traditional urban enclaves (i.e., Chinatown and South Philadelphia) or an emerging enclave with a smaller, but rapidly growing Chinese immigrant population (i.e., the Near Northeast). The remainder was classified as residing in non-enclaves. Results In multivariable adjusted regression models, CRP was inversely associated with dense breast area (p = 0.01). Levels of sTNFR2 were also inversely associated with dense breast area, but these associations varied by neighborhood (interaction p = 0.01); specifically, inverse associations were observed among women residing in the emerging enclave (p = 0.03), but not other neighborhoods. Conclusions Among Chinese immigrant women, aggregate analyses that do not take neighborhood context into consideration can mask potential variations in association of inflammatory markers with breast density. Future studies should consider how neighborhood contextual factors may contribute to differential risk pathways.

Type 2 diabetes and obesity in midlife and breast cancer risk in the Reykjavik cohort Abstract Purpose As obesity and type 2 diabetes (T2D) have been increasing worldwide, we investigated their association with breast cancer incidence in the Reykjavik Study. Methods During 1968–1996, approximately 10,000 women (mean age = 53 ± 9 years) completed questionnaires and donated blood samples. T2D status was classified according to self-report (n = 140) and glucose levels (n  = 154) at cohort entry. A linkage with the Icelandic Cancer Registry provided breast cancer incidence through 2015. Cox regression with age as time metric and adjusted for known confounders was applied to obtain hazard ratios (HR) and 95% confidence intervals (CI). Results Of 9,606 participants, 294 (3.1%) were classified as T2D cases at cohort entry while 728 (7.8%) women were diagnosed with breast cancer during 28.4 ± 11.6 years of follow-up. No significant association of T2D (HR 0.95; 95% CI 0.56–1.53) with breast cancer incidence was detected except among the small number of women with advanced breast cancer (HR 3.30; 95% CI 1.13–9.62). Breast cancer incidence was elevated among overweight/obese women without (HR 1.18; 95% CI 1.01–1.37) and with T2D (HR 1.35; 95% CI 0.79–2.31). Height also predicted higher breast cancer incidence (HR 1.03; 95% CI 1.02–1.05). All findings were confirmed in women of the AGES–Reykjavik sub-cohort (n  = 3,103) who returned for an exam during 2002–2006. With a 10% T2D prevalence and 93 incident breast cancer cases, the HR for T2D was 1.18 (95% CI 0.62–2.27). Conclusions These findings in a population with low T2D incidence suggest that the presence of T2D does not confer additional breast cancer risk and confirm the importance of height and excess body weight as breast cancer risk factors.

Care experiences among dually enrolled older adults with cancer: SEER-CAHPS, 2005–2013 Abstract Purpose Given the associations between poverty and poorer outcomes among older adults with cancer, we sought to understand the effects of dual enrollment in Medicare and Medicaid—as a marker of poverty—on self-reported care experiences among seniors diagnosed with cancer. Methods Retrospective, observational study using cancer registry, Medicare claims, and care experience survey data (Surveillance, Epidemiology, and End Results [SEER]—Consumer Assessment of Healthcare Providers and Systems [CAHPS®]) for a national sample of fee-for-service (FFS) and Medicare Advantage (MA) enrollees aged 65 or older. We included people with one incident primary, malignant cancer diagnosed between 2005 and 2011, surveyed within 2 years after diagnosis (n = 9,800; 995 dual enrollees). Medicare CAHPS measures included 5 global ratings and 3 composite scores. Results After adjustment for potential confounders, people with cancer histories who were dually enrolled were significantly more likely to report better experiences than non-duals on 2 measures (Medicare/their health plan: adjusted odds ratio [aOR]: 0.68, 95% confidence interval [CI] 0.53–0.87; prescription drug plan [PDP]: aOR: 0.54, 95% CI 0.40–0.73). Conclusions Dual enrollees with cancer reported better experiences than Medicare-only enrollees in terms of their health plan (Medicare FFS or Medicare Advantage) and their PDP. Better ratings among dually enrolled beneficiaries suggest possible divergence between health outcomes and care experiences, warranting additional investigation.

Cancer incidence and associations with known risk and protective factors: the Alaska EARTH study Abstract Purpose Cancer is the leading cause of mortality among Alaska Native (AN) people. The Alaska Education and Research Towards Health (EARTH) cohort was established to examine risk and protective factors for chronic diseases, including cancer, among AN people. Here, we describe the cancer experience of the Alaska EARTH cohort in relation to statewide- and region-specific tumor registry data, and assess associations with key cancer risk factors. Methods AN participants were recruited into the Alaska EARTH cohort during 2004–2006. Data collected included patient demographic, anthropometric, medical and family history, and lifestyle information. This study linked the Alaska EARTH data with cancer diagnoses recorded by the Alaska Native Tumor Registry (ANTR) through 12/31/15. We compared EARTH incidence to ANTR statewide incidence. We examined independent associations of smoking status, diet, BMI, and physical activity with incident all-site cancers using multivariable-adjusted Cox proportional hazards models. Results Between study enrollment and 2015, 171 of 3,712 (4.7%) Alaska EARTH study participants were diagnosed with cancer. The leading cancers among Alaska EARTH participants were female breast, lung, and colorectal cancer, which reflected those observed among AN people statewide. Incidence (95% CI) of cancer (all sites) among Alaska EARTH participants was 629.7 (510.9–748.6) per 100,000 person-years; this was comparable to statewide rates [680.5 (660.0–701.5) per 100,000 population]. We observed lower risk of all-sites cancer incidence among never smokers. Conclusions Cancer incidence in the Alaska EARTH cohort was similar to incidence observed statewide. Risk and protective factors for leading cancers among AN people mirror those observed among other populations.

Associations of mammographic breast density with breast stem cell marker-defined breast cancer subtypes Abstract Purpose High mammographic breast density is a strong, well-established breast cancer risk factor. Whether stem cells may explain high breast cancer risk in dense breasts is unknown. We investigated the association between breast density and breast cancer risk by the status of stem cell markers CD44, CD24, and ALDH1A1 in the tumor. Methods We included 223 women with primary invasive or in situ breast cancer and 399 age-matched controls from Mayo Clinic Mammography Study. Percent breast density (PD), absolute dense area (DA), and non-dense area (NDA) were assessed using computer-assisted thresholding technique. Immunohistochemical analysis of the markers was performed on tumor tissue microarrays according to a standard protocol. We used polytomous logistic regression to quantify the associations of breast density measures with breast cancer risk across marker-defined tumor subtypes. Results Of the 223 cancers in the study, 182 were positive for CD44, 83 for CD24 and 52 for ALDH1A1. Associations of PD were not significantly different across t marker-defined subtypes (51% + vs. 11–25%: OR 2.83, 95% CI 1.49–5.37 for CD44+ vs. OR 1.87, 95% CI 0.47–7.51 for CD44−, p-heterogeneity = 0.66; OR 2.80, 95% CI 1.27–6.18 for CD24+ vs. OR 2.44, 95% CI 1.14–5.22 for CD24−, p-heterogeneity = 0.61; OR 3.04, 95% CI 1.14–8.10 for ALDH1A1+ vs. OR 2.57. 95% CI 1.30–5.08 for ALDH1A1−, p-heterogeneity = 0.94). Positive associations of DA and inverse associations of NDA with breast cancer risk were similar across marker-defined subtypes. Conclusions We found no evidence of differential associations of breast density with breast cancer risk by the status of stem cell markers. Further studies in larger study populations are warranted to confirm these associations.