Multi-Systemic Biological Risk and Cancer Mortality: The NHANES III Study.

Multi-systemic biological risk (MSBR), a proxy for allostatic load, is a composite index of biomarkers representing dysregulation due to responses to chronic stress. This study examined the association of an MSBR index with cancer mortality. The sample included n = 13,628 adults aged 20-90 from the NHANES III Linked Mortality File (1988-1994). The MSBR index included autonomic (pulse rate, blood pressure), metabolic (HOMAir, triglycerides, waist circumference), and immune (white blood cell count, C-reactive protein) markers. We fit Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CI) of overall cancer mortality risk, according to quartiles (q) of the index. In multivariable models, compared to those in q1, q4 had a 64% increased risk for cancer mortality (HR = 1.64, 95% CI:1.13-2.40). The immune domain drove the association (HR per unit = 1.19, 95% CI:1.07-1.32). In stratified analyses, the HR for those with a BMI ≥ 25 was 1.12 per unit (95% CI:1.05-1.19) and those with a BMI < 25 was 1.04 per unit (95% CI:0.92-1.18). MSBR is positively associated with risk for cancer mortality in a US sample, particularly among those who are overweight or obese. The utilization of standard clinical measures comprising this index may inform population cancer prevention strategies

Independent and joint cross-sectional associations of statin and metformin use with mammographic breast density

Background Well-tolerated and commonly used medications are increasingly assessed for reducing breast cancer risk. These include metformin and statins, both linked to reduced hormone availability and cell proliferation or growth and sometimes prescribed concurrently. We investigated independent and joint associations of these medications with mammographic breast density (MBD), a useful biomarker for the effect of chemopreventive agents on breast cancer risk. Methods Using data from a cross-sectional study of 770 women (78% Hispanic, aged 40–61 years, in a mammography cohort with high cardiometabolic burden), we examined the association of self-reported “ever” use of statins and metformin with MBD measured via clinical Breast Imaging Reporting and Data System (BI-RADS) density classifications (relative risk regression) and continuous semi-automated percent and size of dense area (Cumulus) (linear regression), adjusted for age, body mass index, education, race, menopausal status, age at first birth, and insulin use. Results We observed high statin (27%), metformin (13%), and combination (9%) use, and most participants were overweight/obese (83%) and parous (87%). Statin use was associated with a lower likelihood of high density BI-RADS (RR = 0.60, 95% CI = 0.45 to 0.80), percent dense area (PD) (β = − 6.56, 95% CI = − 9.05 to − 4.06), and dense area (DA) (β = − 9.05, 95% CI = − 14.89 to − 3.22). Metformin use was associated with lower PD and higher non-dense area (NDA), but associations were attenuated by co-medication with statins. Compared to non-use of either medication, statin use alone or with metformin were associated with lower PD and DA (e.g., β = − 6.86, 95% CI: − 9.67, − 4.05 and β = − 7.07, 95% CI: − 10.97, − 3.17, respectively, for PD) and higher NDA (β = 25.05, 95% CI: 14.06, 36.03; β = 29.76, 95% CI: 14.55, 44.96, respectively). Conclusions Statin use was consistently associated with lower MBD, measured both through clinical radiologist assessment and continuous relative and absolute measures, including dense area. Metformin use was associated with lower PD and higher NDA, but this may be driven by co-medication with statins. These results support that statins may lower MBD but need confirmation with prospective and clinical data to distinguish the results of medication use from that of disease

Multi-Systemic Biological Risk and its Association with Discrimination, Cancer Mortality, and All-Cause Mortality

A multi-systemic biological risk index (MSBR), a proxy for allostatic load, is a composite index of biomarkers that represents dysregulation due to responses to chronic external stress. Research suggests that long term stressful conditions take a toll on one's health, providing the basis for a model that ties external stressors with bio-physiological responses, which in turn influences incidence and prognosis of disease. This dissertation examined three aims that addressed a few gaps in the literature. For one, no previous study has accounted for major sources of chronic stress such as low social support and multiple dimensions of discrimination, which could potentially confound the allostatic load-mortality association. To address this gap we examined the association of MSBR with all-cause mortality in an African-American cohort. Next, while a few previous studies have linked a biological measure of multi-systemic stress with obesity, diabetes, and cardiovascular disease, there is no research that has examined an objective biological measure of multi-systemic stress with cancer outcomes. Lastly, we examined if exposure to discrimination, as measured by a comprehensive discrimination instrument, was associated with multi-systemic biological risk. This dissertation provides new evidence for the strong association between an index of MSBR, (a proxy for allostatic load), and cancer mortality in the NHANES III population. This was particularly evident amongst those who were overweight and obese, and the association was mainly driven by the immune and cardiovascular domains. In the Jackson Heart Study, we found that the MSBR index was positively associated with risk for mortality within an African-American cohort, and the association was higher amongst those of a younger age. This was independent of socioeconomic position, lifestyle risk factors and experiences of discrimination. Lastly, in the CARDIA study we found no association between discrimination or changes in discrimination and the MSBR index. This study provided novel data on the topic of discrimination and objectively measured health risk factors, particularly because we were able to examine change in discrimination with MSBR

Multi-Systemic Biological Risk and its Association with Discrimination, Cancer Mortality, and All-Cause Mortality

A multi-systemic biological risk index (MSBR), a proxy for allostatic load, is a composite index of biomarkers that represents dysregulation due to responses to chronic external stress. Research suggests that long term stressful conditions take a toll on one's health, providing the basis for a model that ties external stressors with bio-physiological responses, which in turn influences incidence and prognosis of disease. This dissertation examined three aims that addressed a few gaps in the literature. For one, no previous study has accounted for major sources of chronic stress such as low social support and multiple dimensions of discrimination, which could potentially confound the allostatic load-mortality association. To address this gap we examined the association of MSBR with all-cause mortality in an African-American cohort. Next, while a few previous studies have linked a biological measure of multi-systemic stress with obesity, diabetes, and cardiovascular disease, there is no research that has examined an objective biological measure of multi-systemic stress with cancer outcomes. Lastly, we examined if exposure to discrimination, as measured by a comprehensive discrimination instrument, was associated with multi-systemic biological risk. This dissertation provides new evidence for the strong association between an index of MSBR, (a proxy for allostatic load), and cancer mortality in the NHANES III population. This was particularly evident amongst those who were overweight and obese, and the association was mainly driven by the immune and cardiovascular domains. In the Jackson Heart Study, we found that the MSBR index was positively associated with risk for mortality within an African-American cohort, and the association was higher amongst those of a younger age. This was independent of socioeconomic position, lifestyle risk factors and experiences of discrimination. Lastly, in the CARDIA study we found no association between discrimination or changes in discrimination and the MSBR index. This study provided novel data on the topic of discrimination and objectively measured health risk factors, particularly because we were able to examine change in discrimination with MSBR

Occupational exposure to endocrine disrupting substances and the risk of breast Cancer: the Singapore Chinese health study

Abstract Background Evidence from basic research links exposure to endocrine disrupting chemicals (EDCs) with a higher risk for breast cancer. However, there is less evidence from observational epidemiological research and the results are equivocal. Therefore, we examined the association between occupational exposure to substances where exposure to EDCs is likely and the risk of breast cancer. Methods A prospective study consisting of a population-based cohort of 33,458 Singaporean Chinese women aged 45–74 years enrolled in the Singapore Chinese Health Study (SCHS) from 1993 to 98 and followed through 2014. Subjects’ self-reported occupational exposure and duration to industries, job titles, and substance types were garnered at baseline, and cases of incident breast cancer (N = 988) were determined by linkage with the Singapore Cancer Registry. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated for exposure to substances, job titles, and industries. Results There was no association between cumulative exposure to substances via occupation where EDC exposure is likely and risk of breast cancer. These results were consistent for hypothesized high (HR 0.94, 95% CI: 0.66–1.35), medium (HR 1.03 95% CI: 0.77–1.38) and low (HR 0.74, 95% CI 0.48–1.13) combined substance exposure groups when compared with those who were not exposed via occupation. Similar null associations were observed when examining job titles and industry categories. Conclusions There was no association between EDC related occupational exposures and breast cancer risk in working women of the Singaporean Chinese Health Study. Future studies that employ rigorous methods with regard to exposure assessment of EDCs are needed

Occupational exposure to endocrine disrupting substances and the risk of breast Cancer: the Singapore Chinese health study.

BackgroundEvidence from basic research links exposure to endocrine disrupting chemicals (EDCs) with a higher risk for breast cancer. However, there is less evidence from observational epidemiological research and the results are equivocal. Therefore, we examined the association between occupational exposure to substances where exposure to EDCs is likely and the risk of breast cancer.MethodsA prospective study consisting of a population-based cohort of 33,458 Singaporean Chinese women aged 45-74 years enrolled in the Singapore Chinese Health Study (SCHS) from 1993 to 98 and followed through 2014. Subjects' self-reported occupational exposure and duration to industries, job titles, and substance types were garnered at baseline, and cases of incident breast cancer (N = 988) were determined by linkage with the Singapore Cancer Registry. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated for exposure to substances, job titles, and industries.ResultsThere was no association between cumulative exposure to substances via occupation where EDC exposure is likely and risk of breast cancer. These results were consistent for hypothesized high (HR 0.94, 95% CI: 0.66-1.35), medium (HR 1.03 95% CI: 0.77-1.38) and low (HR 0.74, 95% CI 0.48-1.13) combined substance exposure groups when compared with those who were not exposed via occupation. Similar null associations were observed when examining job titles and industry categories.ConclusionsThere was no association between EDC related occupational exposures and breast cancer risk in working women of the Singaporean Chinese Health Study. Future studies that employ rigorous methods with regard to exposure assessment of EDCs are needed

Occupational exposure to endocrine disrupting substances and the risk of breast Cancer: the Singapore Chinese health study.

BackgroundEvidence from basic research links exposure to endocrine disrupting chemicals (EDCs) with a higher risk for breast cancer. However, there is less evidence from observational epidemiological research and the results are equivocal. Therefore, we examined the association between occupational exposure to substances where exposure to EDCs is likely and the risk of breast cancer.MethodsA prospective study consisting of a population-based cohort of 33,458 Singaporean Chinese women aged 45-74 years enrolled in the Singapore Chinese Health Study (SCHS) from 1993 to 98 and followed through 2014. Subjects' self-reported occupational exposure and duration to industries, job titles, and substance types were garnered at baseline, and cases of incident breast cancer (N = 988) were determined by linkage with the Singapore Cancer Registry. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated for exposure to substances, job titles, and industries.ResultsThere was no association between cumulative exposure to substances via occupation where EDC exposure is likely and risk of breast cancer. These results were consistent for hypothesized high (HR 0.94, 95% CI: 0.66-1.35), medium (HR 1.03 95% CI: 0.77-1.38) and low (HR 0.74, 95% CI 0.48-1.13) combined substance exposure groups when compared with those who were not exposed via occupation. Similar null associations were observed when examining job titles and industry categories.ConclusionsThere was no association between EDC related occupational exposures and breast cancer risk in working women of the Singaporean Chinese Health Study. Future studies that employ rigorous methods with regard to exposure assessment of EDCs are needed