Breast cancer and exposure to tobacco smoke during potential windows of susceptibility

Purpose: An association between smoking and breast cancer is unresolved, although a higher risk from exposure during windows of susceptibility has been proposed. The objective of this prospective study was to evaluate the association between tobacco smoke and breast cancer with a focus on timing of exposure, especially during early life. Methods: Sister study participants (n = 50,884) aged 35–74 were enrolled from 2003 to 2009. Women in the United States and Puerto Rico were eligible if they were breast cancer-free but had a sister with breast cancer. Participants completed questionnaires on smoking and environmental tobacco smoke (ETS) exposure. Cox regression was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) for breast cancer risk. Results: During follow-up (mean = 6.4 years), 1,843 invasive breast cancers were diagnosed. Neither active smoking nor adult ETS was associated with breast cancer risk. However, never smoking women exposed to ETS throughout their childhood had a 17% higher risk of breast cancer (95% CI 1.00–1.36) relative to those with no exposure. In utero ETS exposure was also associated with breast cancer (HR = 1.16, 95% CI 1.01–1.32) and the HR was most elevated for women born in earlier birth cohorts (<1940, HR = 1.44, 95% CI 1.02–2.02; 1940–1949, HR = 1.28, 95% CI 1.01–1.62). Conclusion: In utero ETS and ETS exposure during childhood and adolescence were associated with increased risk of breast cancer and associations varied by birth cohort

Adult physical activity and breast cancer risk in women with a family history of breast cancer

Background: Recreational physical activity has been consistently associated with reduced breast cancer risk. Less is known about how family history of breast cancer affects the association and whether it varies by menopausal status. Methods: The Sister Study is a cohort of 50,884 women who had a sister with breast cancer but no prior breast cancer themselves at enrollment. Women reported all recreational sport/exercise activities they participated in over the past 12 months. Hours/week and MET-hours/week of physical activity were considered in association with breast cancer risk. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated with Cox regression. Extent of family history, examined as a modifier, was characterized by a Bayesian score incorporating characteristics of the family structure. Results: During follow-up (average 8.4 years), 3,023 cases were diagnosed. Higher hours/week (HR ≥7vs&lt;1 = 0.77; 95% CI, 0.66–0.90) and MET-hours/week (HR quartile4vs1 = 0.75; 95% CI, 0.67–0.85) of physical activity were associated with reduced postmenopausal breast cancer risk. Hours/week and MET-hours/week were associated with suggestively increased premenopausal breast cancer risk (MET-hours/week HR quartile4vs1 = 1.25; 95% CI, 0.98–1.60). Associations did not vary with extent of family history. However, the increased risk in premenopausal women may be limited to those with stronger family history. Conclusions: In women with a family history of breast cancer, physical activity was associated with reduced postmenopausal, but not premenopausal, breast cancer risk and was not modified by extent of family history. Impact: This was the first study to examine the association between physical activity and breast cancer risk in a large population with a family history of breast cancer

Oxidative Stress and Breast Cancer Risk in Premenopausal Women

Detrimental effects of oxidative stress are widely recognized, but induction of apoptosis and senescence may also have benefits for cancer prevention. Recent studies suggest oxidative stress may be associated with lower breast cancer risk before menopause. Methods: We conducted a nested case-control study (N = 457 cases, 910 controls) within the NIEHS Sister Study cohort of 50,884 women. Premenopausal women ages 35-54 were eligible for selection. We matched controls 2:1 to cases on age and enrollment year and were breast cancer-free at the time of the corresponding case's diagnosis. Oxidative stress was measured by urinary F2-isoprostane and metabolite (15-F2t-isoprostane-M) concentrations. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated with multivariable conditional logistic regression. Results: After multivariable adjustment for body mass index (BMI) and other potential confounders, the OR for breast cancer comparing the &gt;90th (≥2.94 ng/mgCr) to &lt;25th percentile (1.01 ng/mgCr) was 1.1 (CI: 0.65, 1.7) for F2-isoprostane and 0.70 (CI: 0.43, 1.1) for the metabolite. Higher metabolite concentrations were associated with lower breast cancer risk among women who were also premenopausal (353 cases, OR: 0.59, CI: 0.34, 1.0) or &lt;46 years (82 cases, OR: 0.15, CI: 0.06, 0.42) at diagnosis. ORs for the metabolite and breast cancer were inverse among women with BMI 18.5-24.9 kg/m2 (OR: 0.47, CI: 0.18, 1.2, 208 cases) and &gt;30 kg/m2 (OR: 0.71, CI: 0.30, 1.7, 107 cases), but not among women with BMI 25-29.9 kg/m2 (OR: 0.98, CI: 0.39, 2.5, 138 cases). Conclusions: Together with other studies, our results support a possible inverse association between oxidative stress and premenopausal breast cancer risk

Airborne mammary carcinogens and breast cancer risk in the Sister Study

Introduction: Potentially carcinogenic hazardous air pollutants (air toxics) have been inconsistently associated with breast cancer. Whether metabolic factors modify these associations is unknown. We studied 29 non-metallic air toxics classified as mammary gland carcinogens in animal studies in relation to breast cancer risk. Methods: Participants included 49,718 women from the Sister Study. Census tract air toxic concentration estimates from the 2005 National Air Toxics Assessment were linked to enrollment residential addresses. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for individual air toxics were estimated using Cox regression. Body mass index (BMI) was considered a potential modifier. Relevant mixtures were identified using classification trees. Results: Over follow-up (average = 8.4 years), 2975 women were newly diagnosed with breast cancer (invasive or ductal carcinoma in situ). Several air toxics, including methylene chloride, polycyclic organic matter, propylene dichloride, and styrene, were associated with increased risk. Of these, methylene chloride was most consistently associated with risk across multiple analyses. It was associated with overall (HRquintile 4vs1 = 1.21 (95%CI = 1.07–1.38)) and estrogen receptor positive (ER+) invasive breast cancer (HRquintile 4vs1 = 1.28 (95%CI = 1.08–1.52)) in individual pollutant models, although no dose-response was observed. Associations were stronger among overweight/obese (vs. non-overweight/obese) women (p &lt; 0.05) for six air toxics. The classification tree identified combinations of age, methylene chloride, BMI, and four other toxics (propylene dichloride, ethylene dibromide, ethylidene dichloride, styrene) related to overall breast cancer. Conclusions: Some non-metallic air toxics, particularly methylene chloride, were associated with the hazard for overall and ER+ breast cancer. Overweight/obese women may be particularly susceptible to air toxics

Pairing Correlations in a Generalized Hubbard Model for the Cuprates

Using numerical diagonalization of a 4x4 cluster, we calculate on-site s, extended s and d pairing correlation functions (PCF) in an effective generalized Hubbard model for the cuprates, with nearest-neighbor correlated hopping and next nearest-neighbor hopping t'. The vertex contributions (VC) to the PCF are significantly enhanced, relative to the t-t'-U model. The behavior of the PCF and their VC, and signatures of anomalous flux quantization, indicate superconductivity in the d-wave channel for moderate doping and in the s-wave channel for high doping and small U.Comment: 5 pages, 5 figure

Hazardous air pollutants and telomere length in the Sister Study

Background: Telomeres are vital for genomic integrity, and telomere length has been linked to many adverse health outcomes. Some hazardous air pollutants or air toxics increase oxidative stress and inflammation, two possible determinants of shortened telomere length. No studies have examined air toxic-Telomere length associations in a nonoccupational setting. Methods: This study included 731 Sister Study participants (enrolled 2003-2007) who were randomly selected to assess telomere length in baseline blood samples. Multiplex qPCR was used to determine telomere to single copy gene (T/S) ratios. Census tract concentration estimates of 29 air toxics from the 2005 National Air Toxics Assessment were linked to baseline residential addresses. Air toxics were classified into tertile-based categories of the exposure. Multivariable linear regression was used to estimate β coefficients and 95% confidence intervals (CIs) in single-pollutant models. Multipollutant groups were identified with regression trees. Results: The average T/S ratio was 1.24. Benzidine (T3 versus T1 β =-0.08; 95% CI =-0.14,-0.01) and 1,4-dioxane (T3 versus T1 β =-0.06; 95% CI =-0.13, 0.00) in particular, as well as carbon tetrachloride, chloroprene, ethylene dibromide, and propylene dichloride, were associated with shorter relative telomere length. Benzidine (P = 0.02) and 1,4-dioxane (P = 0.06) demonstrated some evidence of a monotonic trend. The regression tree identified age, BMI, physical activity, ethylene oxide, acrylonitrile, ethylidene dichloride, propylene dichloride, and styrene in multipollutant groups related to telomere length. Conclusions: In this first study of air toxics and telomere length in a nonoccupational setting, several air toxics, particularly 1,4-dioxane and benzidine, were associated with shorter relative telomere length

Factors associated with breast MRI use among women with a family history of breast cancer

Although annual breast magnetic resonance imaging (MRI) is recommended for women at high risk for breast cancer as an adjunct to screening mammography, breast MRI use remains low. We examined factors associated with breast MRI use in a cohort of women with a family history of breast cancer but no personal cancer history. Study participants came from the Sister Study cohort, a nationwide, prospective study of women with at least 1 sister who had been diagnosed with breast cancer but who themselves had not ever had breast cancer (n = 17 894). Participants were surveyed on breast cancer beliefs, cancer worry, breast MRI use, provider communication, and genetic counseling and testing. Logistic regression was used to assess factors associated with having a breast MRI overall and for those at high risk. Breast MRI was reported by 16.1% and was more common among younger women and those with higher incomes. After adjustment for demographics, ever use of breast MRI was associated with actual and perceived risk. Odds ratios (OR) were 12.29 (95% CI, 8.85-17.06), 2.48 (95% CI, 2.27-2.71), and 2.50 (95% CI, 2.09-2.99) for positive BRCA1/2 test, lifetime breast cancer risk ≥ 20%, and being told by a health care provider of higher risk, respectively. Women who believed they had much higher risk than others or had higher level of worry were twice as likely to have had breast MRI; OR = 2.23 (95% CI, 1.82-2.75) and OR = 1.76 (95% CI, 1.52-2.04). Patterns were similar among women at high risk. Breast cancer risk, provider communication, and personal beliefs were determinants of breast MRI use. To support shared decisions about the use of breast MRI, women could benefit from improved understanding of the chances of getting breast cancer and increased quality of provider communications

Light at night and the risk of breast cancer: Findings from the Sister study

Background: Light at night (LAN) may alter estrogen regulation through circadian disruption. High levels of outdoor LAN may increase breast cancer risk, but studies have largely not considered possible residual confounding from correlated environmental exposures. We evaluated the association between indoor and outdoor LAN and incident breast cancer. Methods: In 47,145 participants in the prospective Sister Study cohort living in the contiguous U.S., exposure to outdoor LAN was determined using satellite-measured residential data and indoor LAN was self-reported (light/TV on, light from outside the room, nightlight, no light). We used Cox proportional hazards models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between outdoor and indoor LAN and breast cancer risk. Models were adjusted for age, race/ethnicity, educational attainment, annual household income, neighborhood disadvantage, latitude, and population density as a proxy for urbanicity. To evaluate the potential for residual confounding of the outdoor LAN and breast cancer relationship by factors associated with urbanicity, we considered further adjustment for exposures correlated with outdoor LAN including NO2 [Spearman correlation coefficient, rho (ρ) = 0.78], PM2.5 (ρ = 0.36), green space (ρ = − 0.41), and noise (ρ = 0.81). Results: During 11 years of follow-up, 3,734 breast cancer cases were identified. Outdoor LAN was modestly, but non-monotonically, associated with a higher risk of breast cancer (Quintile 4 vs 1: HR = 1.10, 95% CI: 0.99–1.22; Quintile 5 vs 1: HR = 1.04, 95% CI: 0.93–1.16); however, no association was evident after adjustment for correlated ambient exposures (Quintile 4 vs 1: HR = 0.99, 95% CI: 0.86–1.14; Quintile 5 vs 1: HR = 0.89, 95% CI: 0.74–1.06). Compared to those with no indoor LAN exposure, sleeping with a light or TV on was associated with a HR = 1.09 (95% CI: 0.97–1.23) in the adjusted model. Conclusions: Outdoor LAN does not appear to increase the risk of breast cancer after adjustment for correlated environmental exposures

Search for the Rare Decay KL --> pi0 ee

The KTeV/E799 experiment at Fermilab has searched for the rare kaon decay KL--> pi0ee. This mode is expected to have a significant CP violating component. The measurement of its branching ratio could support the Standard Model or could indicate the existence of new physics. This letter reports new results from the 1999-2000 data set. One event is observed with an expected background at 0.99 +/- 0.35 events. We set a limit on the branching ratio of 3.5 x 10^(-10) at the 90% confidence level. Combining the results with the dataset taken in 1997 yields the final KTeV result: BR(KL --> pi0 ee) < 2.8 x 10^(-10) at 90% CL.Comment: 4 pages, three figure