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ABSTRACTThe size distribution of adipocytes in fat tissue provides important information about metabolic status and overall health of patients. Histological measurements of biopsied adipose tissue can reveal cardiovascular and/or cancer risks, to complement typical prognosis parameters such as body mass index, hypertension or diabetes. Yet, current methods for adipocyte quantification are problematic and insufficient. Methods such as hand-tracing are tedious and time-consuming, ellipse approximation lacks precision, and fully automated methods have not proven reliable. A semi-automated method fills the gap in goal-directed computational algorithms, specifically for high-throughput adipocyte quantification. Here, we design and develop a tool, AdipoCyze, which incorporates a novel semi-automated tracing algorithm, along with benchmark methods, and use breast histological images from the Komen for the Cure Foundation to assess utility. Speed and precision of the new approach are superior to conventional methods and accuracy is comparable, suggesting a viable option to quantify adipocytes, while increasing user flexibility. This platform is the first to provide multiple methods of quantification in a single tool. Widespread laboratory and clinical use of this program may enhance productivity and performance, and yield insight into patient metabolism, which may help evaluate risks for breast cancer progression in patients with comorbidities of obesity.ABBREVIATIONS:BMI: body mass index.

Prior research suggests that several endogenous hormones in premenopausal women are associated with breast cancer risk; however, few studies have evaluated associations of endogenous hormones with mammographic density (MD) in premenopausal women. We conducted a cross-sectional study of plasma hormone levels in relation to MD among 634 cancer-free premenopausal women in the Nurses’ Health Study II. We measured percent MD from screening mammograms using a computer-assisted method. We assayed estradiol, estrone, and estrone sulfate in blood samples timed in early follicular and mid-luteal phases of the menstrual cycle as well as testosterone, androstenedione, progesterone, dehydroepiandrosterone (DHEA), DHEA sulfate, sex hormone–binding globulin (SHBG), and anti-Müllerian hormone in luteal or untimed samples. We used multivariable linear regression to quantify the association of %MD with quartiles of each hormone, adjusting for age, body mass index, and breast cancer risk factors. Women in the highest quartile of follicular estradiol levels had significantly greater %MD compared to those in the lowest quartile [difference, 6.7 percentage points; 95% confidence interval (CI) 2.2, 11.3; p-trend < 0.001]. Similar associations were observed for follicular free estradiol but not luteal-phase estradiol. Also, women in the top (vs. bottom) quartile of free testosterone had significantly lower %MD (difference, − 4.7; 95% CI − 8.7, − 0.8; p-trend = 0.04). Higher SHBG was significantly associated with higher percent MD (difference, 4.8; 95% CI 1.1, 8.6; p-trend = 0.002). Percent MD was not strongly associated with other measured hormones. Results were similar in analyses that excluded women with anovulatory cycles. Our findings suggest that follicular estradiol and SHBG may play an important role in premenopausal percent MD.

Severe immunosuppression is an established risk factor for non-Hodgkin lymphoma (NHL), but an association with subclinical immune dysfunction is unclear. We conducted a case-control study nested in the Physicians' Health Study and the Nurses' Health Study cohorts to determine whether patterns of antibody response to Epstein-Barr virus (EBV) were associated with NHL risk. We measured antibody titers against viral capsid antigen, early antigen, and Epstein-Barr nuclear antigen (EBNA-1 and EBNA-2) in blood samples collected before diagnosis from 340 cases and 662 matched controls. Using conditional logistic regression, we estimated rate ratios (RRs) and 95% confidence intervals (CIs) for elevated versus normal titers and the ratio of anti–EBNA-1 to anti–EBNA-2 titers (≤ 1.0 vs > 1.0). We found no association between EBV serostatus, elevated titers, or an EBNA-1/EBNA-2 ratio ≤ 1.0 and NHL risk overall. For chronic lymphocytic leukemia/small lymphocytic lymphoma, suggestive associations were noted for elevated anti–EBNA-2 (RR, 1.74; 95% CI, 0.99-3.05), anti–viral capsid antigen (RR, 1.58; 95% CI, 0.79-3.14), and EBNA-1/EBNA-2 ratio ≤ 1.0 (RR, 1.52; 95% CI, 0.91-2.55). There was no evidence of heterogeneity by subtype. Overall, we found no evidence that EBV antibody profile predicts NHL risk in immunocompetent persons, with the possible exception of chronic lymphocytic leukemia/small lymphocytic lymphoma.

Severe immunosuppression is an established risk factor for non-Hodgkin lymphoma (NHL), but an association with subclinical immune dysfunction is unclear. We conducted a case-control study nested in the Physicians' Health Study and the Nurses' Health Study cohorts to determine whether patterns of antibody response to Epstein-Barr virus (EBV) were associated with NHL risk. We measured antibody titers against viral capsid antigen, early antigen, and Epstein-Barr nuclear antigen (EBNA-1 and EBNA-2) in blood samples collected before diagnosis from 340 cases and 662 matched controls. Using conditional logistic regression, we estimated rate ratios (RRs) and 95% confidence intervals (CIs) for elevated versus normal titers and the ratio of anti–EBNA-1 to anti–EBNA-2 titers (≤ 1.0 vs > 1.0). We found no association between EBV serostatus, elevated titers, or an EBNA-1/EBNA-2 ratio ≤ 1.0 and NHL risk overall. For chronic lymphocytic leukemia/small lymphocytic lymphoma, suggestive associations were noted for elevated anti–EBNA-2 (RR, 1.74; 95% CI, 0.99-3.05), anti–viral capsid antigen (RR, 1.58; 95% CI, 0.79-3.14), and EBNA-1/EBNA-2 ratio ≤ 1.0 (RR, 1.52; 95% CI, 0.91-2.55). There was no evidence of heterogeneity by subtype. Overall, we found no evidence that EBV antibody profile predicts NHL risk in immunocompetent persons, with the possible exception of chronic lymphocytic leukemia/small lymphocytic lymphoma.

Environmental exposure to polychlorinated biphenyls (PCBs) and p,p′-dichlorodiphenyldichloroethylene (p, p′-DDE) has been associated with the risk of non-Hodgkin lymphoma.

Two combinations of dilation drops 1% tropicamide and 2.5% phenylephrine (TP) vs. 1% tropicamide and 1% cyclopentolate (TC) were compared to determine time course and magnitude of dilation for patients with dark irides.

Background: The few established risk factors for non-Hodgkin lymphoma (NHL) exhibit considerable heterogeneity by NHL subtype and suggest an etiologic role for factors with immune- or inflammation-modulating properties, or which otherwise influence lymphocyte proliferation and survival. Epidemiologic evidence supports a potential inverse association for fruit and vegetable intake and NHL risk, but with limited subtype-specific evidence. Glucosinates and indole-3-carbinol, both found in cruciferous vegetables, may mediate tumor suppressive effects, including anti-inflammatory and anti-proliferation effects or restoration of phosphatase and tensin homolog (PTEN), a known tumor suppressor frequently down-regulated in cancer cells. We conducted a prospective study to further elucidate the etiologic role of fruit and vegetable consumption for NHL and its most common histologic subtypes.

No relevant conflicts of interest to declare.

Background:Collectively, non-Hodgkin lymphomas (NHL) are expected to account for >95,000 new cancer diagnoses and >24,000 cancer deaths in the United States in 2018. Few NHL risk factors are known other than severe immune compromise, family history of lymphoid malignancies, and some pathogens. Evidence for modifiable risk factors that could inform prevention strategies is limited, especially from prospective studies. An association of anthropometric traits with NHL risk is biologically plausible given the emerging knowledge that obese individuals have heightened inflammation and deregulation of endogenous hormonal pathways that can influence cell cycle control and lymphocyte activation. We undertook the present prospective study to elucidate the associations of young (aged 18-21 years) and usual adult body mass index (BMI), height, weight, and waist circumference with risk of NHL and major histologic subtypes of NHL. The completed analysis will leverage the resources of several large population samples across the United States with prospectively assessed repeated measures of anthropometric traits and high rates of follow-up for disease ascertainment.

Chao: Seattle Genetics: Research Funding.

IMPORTANCE: The association between increasing body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) and risk of breast cancer is unique in cancer epidemiology in that a crossover effect exists, with risk reduction before and risk increase after menopause. The inverse association with premenopausal breast cancer risk is poorly characterized but might be important in the understanding of breast cancer causation. OBJECTIVE: To investigate the association of BMI with premenopausal breast cancer risk, in particular by age at BMI, attained age, risk factors for breast cancer, and tumor characteristics. DESIGN, SETTING, AND PARTICIPANTS: This multicenter analysis used pooled individual-level data from 758 592 premenopausal women from 19 prospective cohorts to estimate hazard ratios (HRs) of premenopausal breast cancer in association with BMI from ages 18 through 54 years using Cox proportional hazards regression analysis. Median follow-up was 9.3 years (interquartile range, 4.9-13.5 years) per participant, with 13 082 incident cases of breast cancer. Participants were recruited from January 1, 1963, through December 31, 2013, and data were analyzed from September 1, 2013, through December 31, 2017. EXPOSURES: Body mass index at ages 18 to 24, 25 to 34, 35 to 44, and 45 to 54 years. MAIN OUTCOMES AND MEASURES: Invasive or in situ premenopausal breast cancer. RESULTS: Among the 758 592 premenopausal women (median age, 40.6 years; interquartile range, 35.2-45.5 years) included in the analysis, inverse linear associations of BMI with breast cancer risk were found that were stronger for BMI at ages 18 to 24 years (HR per 5 kg/m2 [5.0-U] difference, 0.77; 95% CI, 0.73-0.80) than for BMI at ages 45 to 54 years (HR per 5.0-U difference, 0.88; 95% CI, 0.86-0.91). The inverse associations were observed even among nonoverweight women. There was a 4.2-fold risk gradient between the highest and lowest BMI categories (BMI≥35.0 vs &lt;17.0) at ages 18 to 24 years (HR, 0.24; 95% CI, 0.14-0.40). Hazard ratios did not appreciably vary by attained age or between strata of other breast cancer risk factors. Associations were stronger for estrogen receptor–positive and/or progesterone receptor–positive than for hormone receptor–negative breast cancer for BMI at every age group (eg, for BMI at age 18 to 24 years: HR per 5.0-U difference for estrogen receptor–positive and progesterone receptor–positive tumors, 0.76 [95% CI, 0.70-0.81] vs hormone receptor–negative tumors, 0.85 [95% CI: 0.76-0.95]); BMI at ages 25 to 54 years was not consistently associated with triple-negative or hormone receptor–negative breast cancer overall. CONCLUSIONS AND RELEVANCE: The results of this study suggest that increased adiposity is associated with a reduced risk of premenopausal breast cancer at a greater magnitude than previously shown and across the entire distribution of BMI. The strongest associations of risk were observed for BMI in early adulthood. Understanding the biological mechanisms underlying these associations could have important preventive potential.

No relevant conflicts of interest to declare.

Introduction: Circulating fatty acids, which can serve as biomarkers of diet or activity of specific metabolic pathways, may influence non-Hodgkin lymphoma (NHL) risk by modulating inflammation or lymphocyte membrane stability. We performed prospective studies to evaluate red blood cell (RBC) membrane fatty acids as biomarkers of future NHL risk, hypothesizing a positive association for RBC saturated and transfatty acids and an inverse association for polyunsaturated fatty acids (PUFAs) with risk of NHL and major NHL subtypes.

No relevant conflicts of interest to declare.

Introduction: Periodontal disease has been associated with several chronic diseases, including cancer. In an earlier prospective cohort analysis within the HPFS, we observed a 31% higher risk of NHL among participants who reported severe periodontitis at baseline (Michaud et al. Lancet Oncology 2008). Herein, we examined this novel association with an additional 8 years of follow-up, updated periodontal disease status, and analyzed association by subtype of NHL.

Zhang: Takeda Pharmaceuticals Inc: Employment.

No relevant conflicts of interest to declare.

No relevant conflicts of interest to declare.

Background: There is increasing evidence that aspirin reduces the incidence and mortality of several cancers. The results of epidemiologic studies of aspirin in relation to non-Hodgkin lymphoma (NHL) however, are inconsistent, and the association appears to vary by NHL histologic subtype. We aimed to prospectively assess the association between aspirin and major subtypes of NHL in a cohort with detailed data on aspirin use.

Introduction: Severe immune compromise is a strong risk factor for non-Hodgkin lymphoma (NHL), and serum B-cell activation and inflammation markers predicted AIDS-NHL risk in HIV+ persons. We performed a nested case-control analysis in the prospective Nurses’ Health Study (NHS) and Health Professionals Follow-up Study (HPFS) cohorts to characterize pre-diagnosis plasma immune marker profiles associated with risk of HIV-unrelated NHL and major histologic subtypes.

Background: The incidence rate of non-Hodgkin lymphoma (NHL) has more than doubled over the last few decades, but the reason for this increase has been largely unexplained. The long-term effect of blood donation on cancer incidence is not well investigated despite its potentially large impact on the population. Immune deficiency is associated with increased risk of NHL. Blood donation may influence subsequent NHL development via temporary immune system alterations following blood donation, which have been demonstrated in several human studies. A large nested case-control study within a cohort of blood donors in Sweden and Denmark showed an increased odds ratio (OR) of NHL among frequent plasma donors comparing to non-donors (OR 2.14, 95% confidence interval (CI) 1.22-3.74) [Edgren G et al., 2008]. Results of this and other studies have been difficult to interpret because of the possible influence of healthy donor effects or different baseline characteristics among blood donors compared to general population. To test the hypothesis that frequent blood donation is associated with an increased risk of NHL and its most common histologic subtypes in a general, non-immune compromised population, we conducted a prospective study in the Health Professional Follow-up Study (HPFS) cohort.