Polychlorinated biphenyls and their association with survival following breast cancer

Polychlorinated biphenyls (PCBs) are hypothesized to influence breast carcinogenesis due to their persistence and potential to induce estrogenic and anti-estrogenic effects. Whether PCBs influence survival following breast cancer is unknown

Xeroderma pigmentosum complementation group C genotypes/diplotypes play no independent or interaction role with polycyclic aromatic hydrocarbons-DNA adducts for breast cancer risk

Xeroderma pigmentosum complementation group C (XPC) is an important DNA nuclear excision repair (NER) gene that recognizes the damage caused by variety of bulky DNA adducts. We evaluated the association of two common non-synonymous polymorphisms in XPC (Ala499Val and Lys939Gln) with breast cancer risk in the Long Island Breast Cancer Study Project (LIBCSP), a population-based case-control study. Genotyping of 1,067 cases and 1,110 controls was performed by a high throughput assay with fluorescence polarization. There were no overall associations between XPC polymorphisms and breast cancer risk. A diplotype CC-CC was significantly associated with increased breast cancer risk compared with diplotype CA-CA (OR = 1.4, 95%CI: 1.0–1.9), but was not significant when compared with all other diplotypes combined (OR = 1.22, 95%CI: 0.97–1.53). No modification effects were observed for XPC genotypes by cigarette smoking status, smoking pack years or polycyclic aromatic hydrocarbons (PAH) DNA adducts. The increase in breast cancer risk was slightly more pronounced among women with detectable PAH-DNA adducts and carrying the diplotype CC-CC (OR = 1.6, 95%CI: 1.1–2.2) compared to women with non detectable PAH-DNA adducts carrying other diplotypes combined, but no statistically significant interaction was observed (P interaction = 0.69). These data suggest that XPC have neither independent effects nor interactions with cigarette smoking and PAH-DNA adducts for breast cancer risk. Further studies with multiple genetic polymorphisms in NER pathway are warranted

Influence of prediagnostic recreational physical activity on survival from breast cancer

Recreational physical activity (RPA) is associated with a reduced risk of developing breast cancer, but there is limited research on whether prediagnostic RPA influences survival after breast cancer diagnosis

Polycyclic Aromatic Hydrocarbon-DNA Adducts and Breast Cancer: A Pooled Analysis

Polycyclic aromatic hydrocarbon (PAH)-DNA adducts have been associated with breast cancer in several small studies. The authors' pooled analysis included 873 cases and 941 controls from a population-based case-control study. Competitive enzyme-linked immunosorbent assay in peripheral mononuclear cells was conducted in 2 rounds, and results were pooled on the basis of round-specific quantiles. The odds ratio for breast cancer was elevated in relation to detectable PAH-DNA adducts (1.29 as compared with nondetectable adduct levels; 95% confidence interval = 1.05, 1.58), but there was no apparent dose-response relationship with increasing quantiles. No consistent pattern emerged when the results were stratified by PAH sources (e.g., active cigarette smoking or PAH-containing foods), or when the cases were categorized by stage of disease or hormone receptor status. These data provide only modest support for an association between PAH-DNA adducts and breast cancer development

Polycyclic aromatic hydrocarbon–DNA adducts and survival among women with breast cancer

Polycyclic aromatic hydrocarbons (PAH) are mammary carcinogens in animal studies, and a few epidemiologic studies have suggested a link between elevated levels of PAH-DNA adducts and breast cancer incidence. An association between PAH-DNA adducts and survival among breast cancer cases has not been previously reported. We conducted a survival analysis among women with newly diagnosed invasive breast cancer between 1996 and 1997, enrolled in the Long Island Breast Cancer Study Project. DNA was isolated from blood samples that were obtained from cases shortly after diagnosis and before treatment, and assayed for PAH-DNA adducts using an ELISA. Among the 722 cases with PAH-DNA adduct measurements, 97 deaths (13.4%) from all causes and 54 deaths (7.5%) due to breast cancer were reported to the National Death Index (NDI) by December 31, 2002. Using Cox proportional hazards models and controlling for age at diagnosis, we did not find evidence that all-cause mortality (hazard ratio (HR) = 0.88; 95% confidence interval (CI): 0.57–1.37), or breast cancer mortality (HR = 1.20; 95% CI: 0.63–2.28) was strongly associated with detectable PAH-DNA adduct levels compared with non-detectable adducts; additionally, no dose-response association was observed. Among a subgroup with treatment data (n=520), adducts were associated with over a two-fold higher mortality among those receiving radiation, but mortality for adducts was reduced among hormone therapy users. Results from this large population-based study do not provide strong support for an association between detectable PAH-DNA adducts and survival among women with breast cancer, except perhaps among those receiving radiation treatment

Residential Environmental Exposures and other Characteristics Associated with Detectable PAH-DNA Adducts in Peripheral Mononuclear Cells in a Population-Based Sample of Adult Females

The detection of polycyclic aromatic hydrocarbon (PAH)-DNA adducts in human lymphocytes may be useful as a surrogate end point for individual cancer risk prediction. In this study, we examined the relationship between environmental sources of residential PAH, as well as other potential factors that may confound their association with cancer risk, and the detection of PAH-DNA adducts in a large population-based sample of adult women. Adult female residents of Long Island, New York, aged at least 20 years were identified from the general population between August 1996 and July 1997. Among 1556 women who completed a structured questionnaire, 941 donated sufficient blood (25+ ml) to allow use of a competitive ELISA for measurement of PAH-DNA adducts in peripheral blood mononuclear cells. Ambient PAH exposure at the current residence was estimated using geographic modeling (n=796). Environmental home samples of dust (n=356) and soil (n=360) were collected on a random subset of long-term residents (15+ years). Multivariable regression was conducted to obtain the best-fitting predictive models. Three separate models were constructed based on data from : (A) the questionnaire, including a dietary history; (B) environmental home samples; and (C) geographic modeling. Women who donated blood in summer and fall had increased odds of detectable PAH-DNA adducts (OR=2.65, 95% confidence interval (CI)=1.69, 4.17; OR=1.59, 95% CI=1.08, 2.32, respectively), as did current and past smokers (OR=1.50, 95% CI=1.00, 2.24; OR=1.46, 95% CI=1.05, 2.02, respectively). There were inconsistent associations between detectable PAH-DNA adducts and other known sources of residential PAH, such as grilled and smoked foods, or a summary measure of total dietary benzo-[a]-pyrene (BaP) intake during the year prior to the interview. Detectable PAH-DNA adducts were inversely associated with increased BaP levels in dust in the home, but positively associated with BaP levels in soil outside of the home, although CIs were wide. Ambient BaP estimates from the geographic model were not associated with detectable PAH-DNA adducts. These data suggest that PAH-DNA adducts detected in a population-based sample of adult women with ambient exposure levels reflect some key residential PAH exposure sources assessed in this study, such as cigarette smoking

PAH-DNA Adducts, Cigarette Smoking, \u3cem\u3eGST\u3c/em\u3e Polymorphisms, and Breast Cancer Risk

BACKGROUND: Polycyclic aromatic hydrocarbon (PAHs) may increase breast cancer risk, and the association may be modified by inherited differences in deactivation of PAH intermediates by glutathione S-transferases (GSTs). Few breast cancer studies have investigated the joint effects of multiple GSTs and a PAH biomarker. OBJECTIVE: We estimated the breast cancer risk associated with multiple polymorphisms in the GST gene (GSTA1, GSTM1, GSTP1, and GSTT1) and the interaction with PAH-DNA adducts and cigarette smoke. METHODS: We conducted unconditional logistic regression using data from a population-based sample of women (cases/controls, respectively): GST polymorphisms were genotyped using polymerase chain reaction and matrix-assisted laser desorption/ionization time-of-flight assays (n = 926 of 916), PAH-DNA adduct blood levels were measured by competitive enzyme-linked immunosorbent assay (n = 873 of 941), and smoking status was assessed by in-person questionnaires (n = 943 of 973). RESULTS: Odds ratios for joint effects on breast cancer risk among women with at least three variant alleles were 1.56 [95% confidence interval (CI), 1.13-2.16] for detectable PAH-DNA adducts and 0.93 (95% CI, 0.56-1.56) for no detectable adducts; corresponding odds ratios for three or more variants were 1.18 (95% CI, 0.82-1.69) for ever smokers and 1.44 (95% CI, 0.97-2.14) for never smokers. Neither interaction was statistically significant (p = 0.43 and 0.62, respectively). CONCLUSION: We found little statistical evidence that PAHs interacted with GSTT1, GSTM1, GSTP1, and GSTA1 polymorphisms to further increase breast cancer risk

PAH–DNA Adducts, Cigarette Smoking, GST Polymorphisms, and Breast Cancer Risk

BackgroundPolycyclic aromatic hydrocarbons (PAHs) may increase breast cancer risk, and the association may be modified by inherited differences in deactivation of PAH intermediates by glutathione S-transferases (GSTs). Few breast cancer studies have investigated the joint effects of multiple GSTs and a PAH biomarker.ObjectiveWe estimated the breast cancer risk associated with multiple polymorphisms in the GST gene (GSTA1, GSTM1, GSTP1, and GSTT1) and the interaction with PAH–DNA adducts and cigarette smoking.MethodsWe conducted unconditional logistic regression using data from a population-based sample of women (cases/controls, respectively): GST polymorphisms were genotyped using polymerase chain reaction and matrix-assisted laser desorption/ionization time-of-flight assays (n = 926 of 916), PAH–DNA adduct blood levels were measured by competitive enzyme-linked immunosorbent assay (n = 873 of 941), and smoking status was assessed by in-person questionnaires (n = 943 of 973).ResultsOdds ratios for joint effects on breast cancer risk among women with at least three variant alleles were 1.56 [95% confidence interval (CI), 1.13–2.16] for detectable PAH–DNA adducts and 0.93 (95% CI, 0.56–1.56) for no detectable adducts; corresponding odds ratios for three or more variants were 1.18 (95% CI, 0.82–1.69) for ever smokers and 1.44 (95% CI, 0.97–2.14) for never smokers. Neither interaction was statistically significant (p = 0.43 and 0.62, respectively).ConclusionWe found little statistical evidence that PAHs interacted with GSTT1, GSTM1, GSTP1, and GSTA1 polymorphisms to further increase breast cancer risk