Abstract Mammographic density (MD) is positively associated with breast cancer risk and with breast cancer recurrence. Factors that influence MD include age, circulating endogenous hormone levels, hormone therapy, menopausal status, parity, adiposity, and genetic variation. The association between MD and estrogen levels may be regulated to an extent by the immune system. Cytokines such as IL-6 influence aromatase activity and therefore estrogen synthesis. Experiments on breast cancer cell lines have shown that IL-6, in combination with estrone sulfate enhances cellular proliferation through their action on aromatase. Acute phase proteins C-Reactive Protein (CRP) and Serum Amyloid A (SAA) are nonspecific inflammatory markers that increase with systemic inflammation in response to elevated levels of IL-6. The purpose of this study is to evaluate whether CRP or SAA are associated with MD among postmenopausal women who are breast cancer survivors. Circulating levels of CRP, SAA, and percent MD approximately 30 months after diagnosis were obtained from 479 women participating in the Health, Eating, Activity, and Lifestyle Study (HEAL). HEAL is a prospective cohort study of 1,183 breast cancer survivors identified through Surveillance, Epidemiology, and End Results registries in Los Angeles County, New Mexico, and Western Washington. For this analysis, regression models were used to estimate associations between CRP/SAA and MD after adjustments for age, race, body mass index (BMI), post-menopausal hormone use, tamoxifen use, and study center. Potential effect modification by factors that could influence inflammation or estrogen levels was evaluated by stratification and with formal tests of interaction. After adjusting for covariates, we found a negative association between CRP and MD (β=-0.13, p=0.03) and no association between SAA and MD (β=-0.09, p=0.31). These associations were not modified by race, use of non-steroidal anti-inflammatory drug, smoking, or physical activity. Further, we found that women with CRP levels that were lower than the median (<2.4 CRP mg/L) had higher geometric mean percent MD than women at or above the median; this association was consistent across 5-year age groups. The largest association between CRP and MD was found among women <50 years of age (β=-0.33, p=.01) although there was no statistically significant interaction between CRP and age. Our results suggest CRP is inversely associated with MD after adjusting for BMI and other covariates. These findings should be confirmed in independent disease free population that includes direct measures of cytokine activity such as IL-6. Additional exploration of biological mechanism is needed. Citation Format: Anne Dee, Roberta McKean-Cowdin, Anne McTiernan, Richard N. Baumgartner, Kathy B. Baumgartner, Rachel Ballard-Barbash, Leslie Bernstein. Acute-phase proteins (C-reactive protein and Serum Amyloid A) and post-diagnosis mammographic density in breast cancer survivors. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr B87.
The incidence of pediatric brain tumors varies by race and ethnicity, but these relationships may be confounded by socioeconomic status (SES). In this study, the Surveillance, Epidemiology, and End Results Program (SEER) database was evaluated for associations between race/ethnicity and pediatric glioma and medulloblastoma risk with adjustment for SES.Pediatric glioma and medulloblastoma cases from the SEER database (years: 2000-2016) were included. Differences in incidence rates by ethnicity, sex, age, and SES-related factors were evaluated by calculation of age-adjusted incidence rates (AAIRs) and annual percent change (APC). SES-related factors (percentage without less than high school graduation, median household income, and percentage foreign-born) were derived from the census at the county-level (year: 2000). Multivariable Poisson regression models with adjustment for selected covariates were constructed to evaluate risk factors.The highest AAIRs of pediatric glioma were observed among non-Hispanic Whites (AAIR: 2.91 per 100 000, 95%-CI: 2.84-2.99). An increasing incidence of pediatric glioma by calendar time was observed among non-Hispanic Whites and non-Hispanic Blacks (APC: 0.97%, 95%-CI: 0.28-1.68 and APC: 1.59%, 95%-CI: 0.03-3.18, respectively). Hispanic and non-Hispanic Black race/ethnicity was associated with lower risk when compared with non-Hispanic White (incidence rate ratios [IRRs]: 0.66, 95%-CI: 0.63-0.70; and 0.69, 95%-CI: 0.65-0.74, respectively). For medulloblastoma, the highest AAIR was observed for non-Hispanic Whites with a positive APC (1.52%, 95%-CI: 0.15-2.91). Hispanics and non-Hispanic Blacks had statistically significant lower IRRs compared with non-Hispanic Whites (IRRs: 0.83, 95%-CI: 0.73-0.94; and 0.72, 95%-CI: 0.59-0.87, respectively).Non-Hispanic White race/ethnicity was associated with higher pediatric glioma and medulloblastoma IRRs in models with adjustments for SES.
Abstract Background C-reactive protein (CRP) and Serum amyloid A protein (SAA) increases with systemic inflammation and are related to worse survival for breast cancer survivors. This study examines the association between percent body fat and SAA and CRP and the potential interaction with NSAID use and weight change. Methods Participants included 134 non-Hispanic white and Hispanic breast cancer survivors from the Health, Eating, Activity, and Lifestyle Study. Body fat percentage, measured with Dual Energy X-ray Absorptiometer (DEXA), and circulating levels of CRP and SAA were obtained 30 months after breast cancer diagnosis. Results Circulating concentrations of CRP and SAA were associated with increased adiposity as measured by DEXA after adjustment for age at 24-months, race/ethnicity, dietary energy intake, weight change, and NSAID use. Survivors with higher body fat ≥35% had significantly higher concentrations of CRP (2.01 mg/l vs. 0.85 mg/l) and SAA (6.21 mg/l vs. 4.21 mg/l) compared to non-obese (body fat < 35%). Women who had gained more than 5% of their body weight since breast cancer diagnosis had non-statistically significant higher geometric mean levels of CRP and SAA. Mean levels of CRP and SAA were higher among obese women who were non-users of NSAIDs compared to current users; the association with SAA reached statistical significance (Mean SAA = 7.24, 95%CI 6.13-8.56 for non-NSAID; vs. 4.87; 95%CI 3.95-6.0 for NSAID users respectively). Conclusions Breast cancer survivors with higher body fat had higher mean concentrations of CRP and SAA than women with lower body fat. Further assessment of NSAID use and weight control in reducing circulating inflammatory markers among survivors may be worthwhile to investigate in randomized intervention trials as higher inflammatory markers are associated with worse survival.
Background: Weight gain and obesity are associated with increased risk of postmenopausal breast cancer. Further, women who develop breast cancer and are obese have a poorer prognosis compared to women of normal weight. Regular mammography every 1–2 years has been recommended by many organizations as the gold standard for early breast cancer detection, but adherence to these recommendations may differ both by weight and race/ethnicity. In the Hawaii and Los Angeles Multiethnic Cohort (MEC) Study, only 53% of non-Hispanic White, 49% of Japanese American, 45% of Native Hawaiian, 42% of Hispanic and 44% of African American women reported having had a mammography regularly every 1–2 years over a 6-year period of follow-up. Purpose: The purpose of this study was to describe the association between body mass index (BMI) and frequency of regular mammography over an approximate 6-year period within this study after controlling for the influence of demographic and behavioral factors, and medical history. This association was examined overall and by race/ethnicity in a multiethnic cohort of women aged 45–74 years including African American, Japanese American, Hispanic, Native Hawaiian, and non-Hispanic White women. Data Analysis: The data analysis included 81,722 women from the Hawaii and Los Angeles MEC. Unconditional logistic regression was used to assess the association between BMI and regular annual or biennial (every 1–2 years) mammography overall and by race/ethnicity. Findings: The findings of the study revealed approximately 71% of MEC African American women were overweight or obese (body mass index [BMI] ≥ 25 kg/m2), followed by Native Hawaiian (65%); Hispanic (64%), non-Hispanic White (42%) and Japanese American (27%) women. Women who were overweight (OR=0.96; 95% CI 0.92–1.01) or obese (OR=0.88; 95% CI 0.84–0.93) were less likely to have regular annual mammography compared to women of normal weight. With the exception of Japanese Americans, the odds of having regular annual mammography was lower for women with BMI ≥ 25 kg/m2 compared to normal BMI for each racial/ethnic group; this association was statistically significant for non-Hispanic White, Native Hawaiian and African American women (p Conclusions: BMI is negatively associated with regular annual and biennial mammography in multiethnic women warranting the need for culturally sensitive educational strategies that promote healthy behaviors toward regular mammography and maintenance of normal BMI.
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