Improving Organochlorine Biomarker Models for Cancer Research

Abstract

Multivariate methods were used to predict levels of dichlorodiphenyldichloroethene (DDE) and polychlorinated biphenyl (PCB) concentrations in plasma from characteristics that included age, diet, race, reproductive history, socioeconomic status, and reported body mass index (BMI) at several decades of life before blood collection. Measurements were available for organochlorine compound (organochlorines), cholesterol, and triglycerides in plasma from 1,008 women participants in a population-based case-control study of breast cancer undertaken in 1996 to 1997 on Long Island, NY. Organochlorine compound levels were associated with age, race, lactation history, body size characteristics, and plasma lipids. PCB predictors also included fish consumption. DDE was correlated with current BMI, BMI at every decade of age from ages 20 to 60 years, and BMI-gain (from ages 20 or 30 years to 1997). In contrast, PCBs were correlated inversely with both BMI (fifth to seventh decades of age) and BMI-gain. After adjusting for covariates, DDE and PCB were both positively associated with BMI and inversely with BMI-gain; they were lowest with low BMI, high BMI-gain, and longer lactation. This pattern is consistent with a pharmacokinetic model that predicts higher body burdens during windows of highest uptake, faster elimination of organochlorine compounds in leaner women, and lowered levels accompanying BMI-gain. As a result, lifetime intake for specific organochlorine compound may lead to different plasma levels dependent on changes in body size, absolute intensity of intake, and whether exposure is ongoing (i.e., PCB) or long discontinued (i.e., DDE). (Cancer Epidemiol Biomarkers Prev 2005;14(9):2224 -36)

Estimating the half-lives of PCB congeners in former capacitor workers measured over a 28-year interval

“…Examination of the relationships between 2004 serum PCB concentrations and demographic variables provides additional insights, as well as confirming that the results reported here are similar to those found in previous studies. Current serum PCB concentrations were significantly and positively associated with the age of the individual, a finding that has been previously reported (Wolff et al, 2005). There were also significant gender differences in current serum lipid-adjusted PCB concentrations, with men in our cohort having higher serum PCB concentrations than women.…”

Pharmacokinetic Variability and Modern Epidemiology—The Example of Dichlorodiphenyltrichloroethane, Body Mass Index, and Birth Cohort

“…For example, in two breast cancer cohorts of older women (ref. 8 and unpublished data from ref. 15), both DDE and PCB were positively associated with BMI, but negatively associated with weight gain in multivariate linear regression models.…”

“…In Fig. 2, intensity was derived from reported levels of dietary and ambient DDT contamination in the United States, which peaked around 1965 (8). During a long interval of exposure involving uptake and elimination, weight gain will differ for each birth cohort, and this will alter correlations of HHC with BMI at the time of HHC measurement for different cohorts.…”

“…Weight gain surely would be greatest for the oldest cohort. Although weight loss reduces HHC levels and shortens half-life, only a small proportion of individuals lose weight over time (8,12). However, weight loss may pose a serious problem for HHC measurement near the time of diagnosis for some cancers (16,17).…”

DDT and Breast Cancer

“…Nonetheless, if the effect of DDT exposure early in life on breast cancer risk is large [a possibility suggested by Cohn et al (2007)], then the decreasing birth cohort trend in breast cancer risk that has been observed for U.S. baby boomers is even more remarkable (Chu et al 1999; Tarone 2006, 2007; Tarone and Chu 2000). Women born after 1945 would have been exposed to DDT for each of the first 13 years of life, with increasing exposure through the late 1960s (Wolff et al 2005), but the birth cohort risk of breast cancer showed a marked decrease among U.S. women for over two decades after 1945. DDT exposure would join a list of other breast cancer risk factors predicting increasing breast cancer risk in baby boomers (Tarone 2006); yet the birth cohort risk of breast cancer decreased for women born after 1945.…”