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

Fat or fit: The joint effects of physical activity, weight gain, and body size on breast cancer risk

While physical activity reduces breast cancer risk, issues critical to providing clear public health messages remain to be elucidated. These include: the minimum duration and intensity necessary for risk reduction; the optimal time period for occurrence; as well as subgroup effects, particularly with regard to tumor heterogeneity and body size

Common genetic variations in the LEP and LEPR genes, obesity and breast cancer incidence and survival

Obesity is a strong risk factor for breast cancer in postmenopausal women and adverse prognostic indicator regardless of menopausal status. Leptin is an important regulator of adipose tissue mass and has been associated with tumor cell growth. Leptin exerts its effects through interaction with the leptin receptor (LEPR). We investigated whether genetic variations in the leptin (LEP) and LEPR genes are associated with risk of breast cancer, or once diagnosed, with survival

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

Organochlorine insecticides DDT and chlordane in relation to survival following breast cancer: Organochlorine Insecticides and Breast Cancer

Organochlorine insecticides have been studied extensively in relation to breast cancer incidence and results from two meta-analyses have been null for late-life residues, possibly due to measurement error. Whether these compounds influence survival remains to be fully explored. We examined associations between organochlorine insecticides (p,p’-DDT, its primary metabolite, p,p’-DDE, and chlordane) assessed shortly after diagnosis and survival among women with breast cancer. A population-based sample of women diagnosed with a first primary invasive or in situ breast cancer in 1996–1997 and with available organochlorine blood measures (n=633) were followed for vital status through 2011. After follow-up of 5 and 15 years, we identified 55 and 189 deaths, of which 36 and 74, respectively, were breast cancer-related. Using Cox regression models, we estimated the multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for lipid-adjusted organochlorine concentrations with all-cause and breast cancer-specific mortality. At 5 years after diagnosis, the highest tertile of DDT concentration was associated with all-cause (HR=2.19; 95%CI: 1.02, 4.67) and breast cancer-specific (HR=2.72; 95%CI: 1.04, 7.13) mortality. At 15 years, middle tertile concentrations of DDT (HR=1.42; CI 0.99, 2.06) and chlordane (HR=1.42; 95%CI: 0.94, 2.12) were modestly associated with all-cause and breast cancer-specific mortality. Third tertile DDE concentrations were inversely associated with 15-year all-cause mortality (HR=0.66; 95%CI: 0.44, 0.99). This is the first population-based study in the United States to show that DDT may adversely impact survival following breast cancer diagnosis. Further studies are warranted given the high breast cancer burden and the ubiquity of these chemicals

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

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

Plasma protein carbonyl levels and breast cancer risk

AbstractTo study the role of oxidative stress in breast cancer risk, we analysed plasma levels of protein carbonyls in 1050 cases and 1107 controls. We found a statistically significant trend in breast cancer risk in relation to increasing quartiles of plasma protein carbonyl levels (OR = 1.2, 95% CI = 0.9–1.5; OR = 1.5, 95% CI = 1.2–2.0; OR = 1.6, 95% CI = 1.2–2.1, for the 2nd, 3rd and 4th quartile relative to the lowest quartile, respectively, P for trend = 0.0001). The increase in risk was similar for younger (30 grams per day. Women with higher levels of plasma protein carbonyl and urinary 15F2t-isoprostane had an 80% increase in breast cancer risk (OR = 1.8, 95% CI = 1.2–2.6) compared to women with levels below the median for both markers of oxidative stress. In summary, our results suggest that increased plasma protein carbonyl levels may be associated with breast cancer risk