Search

Purpose: Racial/ethnic minorities are often assumed to be less willing to participate in and provide biospecimens for biomedical research. We examined racial/ethnic differences in enrollment of women with breast cancer (probands) and their first-degree relatives in the Northern California site of the Breast Cancer Family Registry from 1996 to 2011.Methods: We evaluated participation in several study components, including biospecimen collection, for probands and relatives by race/ethnicity, cancer history, and other factors.Results: Of 4,780 eligible probands, 76% enrolled in the family registry by completing the family history and risk factor questionnaires and 68% also provided a blood or mouthwash sample. Enrollment was highest (81%) for non-Hispanic whites (NHWs) and intermediate (73-76%) for Hispanics, African Americans, and all Asian American subgroups, except Filipina women (66%). Of 4,279 eligible relatives, 77% enrolled in the family registry, and 65% also provided a biospecimen sample. Enrollment was highest for NHWs (87%) and lowest for Chinese (68%) and Filipinas (67%). Among those enrolled, biospecimen collection rates were similar for NHW, Hispanic, and African American women, both for probands (92-95%) and relatives (82-87%), but lower for some Asian-American subgroups (probands: 72-88%; relatives: 71-88%), foreign-born Asian Americans, and probands those who were more recent immigrants or had low English language proficiency.Conclusions: These results show that racial/ethnic minority populations are willing to provide biospecimen samples for research, although some Asian American subgroups in particular may need more directed recruitment methods. To address long-standing and well-documented cancer health disparities, minority populations need equal opportunities to contribute to biomedical research. [ABSTRACT FROM AUTHOR]

We propose a cost-effective sampling design and estimating procedure for validating personal risk models using right-censored cohort data. Validation involves using each subject's covariates, as ascertained at cohort entry, in a risk model (specified independently of the data) to assign him/her a probability of an adverse outcome within a future time period. Subjects are then grouped according to the magnitudes of their assigned risks, and within each group, the mean assigned risk is compared with the probability of outcome occurrence as estimated using the follow-up data. Such validation presents two complications. First, in the presence of right-censoring, estimating the probability of developing the outcomes before death requires competing risk analysis. Second, for rare outcomes, validation using the full cohort requires assembling covariates and assigning risks to thousands of subjects. This can be costly when some covariates involve analyzing biological specimens. A two-stage sampling design addresses this problem by assembling covariates and assigning risks only to those subjects most informative for estimating key parameters. We use this design to estimate the outcome probabilities needed to evaluate model performance and we provide theoretical and bootstrap estimates of their variances. We also describe how to choose two-stage designs with minimal efficiency loss for a parameter of interest when the quantities determining optimality are unknown at the time of design. We illustrate these methods by using subjects in the California Teachers Study to validate ovarian cancer risk models. We find that a design with optimal efficiency for one performance parameter need not be so for others, and trade-offs will be required. A two-stage design that samples all outcome-positive subjects and more outcome-negative than censored subjects will perform well in most circumstances. The methods are implemented in Risk Model Assessment Program, an R program freely available at http://med.stanford.edu/epidemiology/two-stage.html. [ABSTRACT FROM AUTHOR]

Background: A previous Australian population-based breast cancer case-control study found indirect evidence that control participation, although high, was not random. We hypothesized that unaffected sisters may provide a more appropriate comparison group than unrelated population controls.Methods: Three population-based case-control-family studies of breast cancer in women of white European origin were carried out by the Australian, Ontario and Northern California sites of the Breast Cancer Family Registry. We compared risk factors between 3643 cases, 2444 of their unaffected sisters and 2877 population controls and conducted separate case-control analyses based on population and sister controls using unconditional multivariable logistic regression.Results: Compared with sister controls, population controls were more highly educated, had an earlier age at menarche, fewer births, their first birth at a later age and their last birth more recently. The established breast cancer associations detected using sister controls, but not detected using population controls, were decreasing risk with each of later age at menarche, more births, younger age at first birth and greater time since last birth.Conclusions: Since participation of population controls might be unintentionally related to some risk factors, we hypothesize that sister controls could provide more valid relative risk estimates and be recruited at lower cost. Given declining study participation by population controls, this contention is highly relevant to epidemiologic research. [ABSTRACT FROM AUTHOR]

Objective: Chloral hydrate, used as a hypnosedative in adults and children, has been shown to be genotoxic and carcinogenic in animal studies. We investigated the potential causal association between chloral hydrate exposure and cancer risk in humans.Methods: Cancer incidence was previously determined via biennial screening analyses of the 215 most commonly used drugs between 1976 and 1998 for a cohort of 143,574 outpatients at Kaiser Permanente who had prescriptions filled between 1969 and 1973. Among users of chloral hydrate, statistically significant elevations in standardised morbidity ratios were observed during various years for cancer at five anatomical sites, including the lung, stomach, prostate, skin melanoma and mouth floor. In this analysis, these associations were investigated using: (i) a dose-response analysis among exposed subjects; and (ii) a two-stage design with exposed and non-exposed persons.Results: There was evidence of an increasing risk of prostate cancer with increasing number of dispensings of chloral hydrate, which persisted after controlling for benign prostatic hypertrophy, vasectomy and obesity; however, the trend was not statistically significant. There was no evidence of a dose-response relationship between chloral hydrate and risk of any of the other four cancers. In the two-stage design, analyses comparing exposed and unexposed subjects showed no increased risk of cancer after controlling for confounding variables; however, the data were suggestive for prostate cancer, where the increased risk associated with chloral hydrate exposure after adjustment for confounding variables persisted. No dose-response relationship was seen for any of the other four cancer sites.Conclusions: To our knowledge, this is the first study to examine the relationship between chloral hydrate exposure and cancer risk in humans. There was no persuasive evidence to support a causal relationship between chloral hydrate exposure in humans and the development of cancer. However, statistical power was low for weak associations, particularly for some of the individual cancer sites. Although animal data using much higher doses of chloral hydrate have demonstrated its genotoxicity and carcinogenicity, the effects of chloral hydrate in humans are still uncertain. [ABSTRACT FROM AUTHOR]

Abstract: Daily asthma attack diaries of 16 panels of asthmatics residing in the Los Angeles area were collected by the Environmental Protection Agency for 34-week periods during the years 1972-1975. These date are examined here for the relationship between daily attack occurrence and daily levels of photochemical oxidant. Total suspended particulates, minimum temperature, relative humidity, and average wind speed. A separate multiple logistic regression is used for each panelist's attack data. Variables representing the presence or absence of attack on the preceding day, as well as day of week and time since the start of the study, are included in the regressions. The most significant predictor of attacks was the presence of an attack on the preceding day. On the average, the panelists tended to have increased attacks on days with high oxidant and particulate pollution on cool days, and during the first two months of the study. Panelists' attack propensity also differed by day of week in particular they had more attacks on Saturdays (the last day of the weekly reporting period) than on Sundays. Each panelist's regression coefficients are classified according to age, sex, hay fever status, and self-assessed attack precursors: this classification is used to examine subgroups among the panelists with high co-efficients corresponding to the above factors. (Am J Public Health 1980: 70:687-696.) [ABSTRACT FROM AUTHOR]

Background: Full-field digital mammography (FFDM) has largely replaced film-screen mammography in the US. Breast density assessed from film mammograms is strongly associated with breast cancer risk, but data are limited for processed FFDM images used for clinical care.Methods: We conducted a case-control study nested among non-Hispanic white female participants of the Research Program in Genes, Environment and Health of Kaiser Permanente Northern California who were aged 40 to 74 years and had screening mammograms acquired on Hologic FFDM machines. Cases (n = 297) were women with a first invasive breast cancer diagnosed after a screening FFDM. For each case, up to five controls (n = 1149) were selected, matched on age and year of FFDM and image batch number, and who were still under follow-up and without a history of breast cancer at the age of diagnosis of the matched case. Percent density (PD) and dense area (DA) were assessed by a radiological technologist using Cumulus. Conditional logistic regression was used to estimate odds ratios (ORs) for breast cancer associated with PD and DA, modeled continuously in standard deviation (SD) increments and categorically in quintiles, after adjusting for body mass index, parity, first-degree family history of breast cancer, breast area, and menopausal hormone use.Results: Median intra-reader reproducibility was high with a Pearson's r of 0.956 (range 0.902 to 0.983) for replicate PD measurements across 23 image batches. The overall mean was 20.02 (SD, 14.61) for PD and 27.63 cm(2) (18.22 cm(2)) for DA. The adjusted ORs for breast cancer associated with each SD increment were 1.70 (95 % confidence interval, 1.41-2.04) for PD, and 1.54 (1.34-1.77) for DA. The adjusted ORs for each quintile were: 1.00 (ref.), 1.49 (0.91-2.45), 2.57 (1.54-4.30), 3.22 (1.91-5.43), 4.88 (2.78-8.55) for PD, and 1.00 (ref.), 1.43 (0.85-2.40), 2.53 (1.53-4.19), 2.85 (1.73-4.69), 3.48 (2.14-5.65) for DA.Conclusions: PD and DA measured using Cumulus on processed FFDM images are positively associated with breast cancer risk, with similar magnitudes of association as previously reported for film-screen mammograms. Processed digital mammograms acquired for routine clinical care in a general practice setting are suitable for breast density and cancer research. [ABSTRACT FROM AUTHOR]

[Display omitted] Within the Multiethnic Cohort (MEC), we examined the association between air pollution and mortality among African American, European American, Japanese American, and Latina American women diagnosed with breast cancer. We used a land use regression (LUR) model and kriging interpolation to estimate nitrogen oxides (NO x , NO 2) and particulate matter (PM 2.5 , PM 10) exposures for 3,089 breast cancer cases in the MEC, who were diagnosed from 1993 through 2013 and resided largely in Los Angeles County, California. Cox proportional hazards models were used to examine the association of time-varying air pollutants with all-cause, breast cancer, cardiovascular disease (CVD), and non-breast cancer/non-CVD mortality, accounting for key covariates. We identified 1,125 deaths from all causes (474 breast cancer, 272 CVD, 379 non-breast cancer/non-CVD deaths) among the 3,089 breast cancer cases with 8.1 years of average follow-up. LUR and kriged NO X (per 50 ppb) and NO 2 (per 20 ppb), PM 2.5 (per 10 µg/m3), and PM 10 (per 10 µg/m3) were positively associated with risks of all-cause (Hazard Ratio (HR) range = 1.13–1.25), breast cancer (HR range = 1.19–1.45), and CVD mortality (HR range = 1.37–1.60). Associations were statistically significant for LUR NO X and CVD mortality (HR = 1.60; 95% CI: 1.08–2.37) and kriged NO 2 and breast cancer mortality (HR = 1.45; 95% CI 1.02–2.07). Gaseous and PM pollutants were positively associated with breast cancer mortality across racial/ethnic group. In this study, air pollutants have a harmful impact on breast cancer survival. Additional studies should evaluate potential confounding by socioeconomic factors. These data support maintaining clean air laws to improve survival for women with breast cancer. [ABSTRACT FROM AUTHOR]

Previous studies using different exposure methods to assess air pollution and breast cancer risk among primarily whites have been inconclusive. Air pollutant exposures of particulate matter and oxides of nitrogen were estimated by kriging (NO x , NO 2 , PM 10 , PM 2.5 ), land use regression (LUR, NO x , NO 2 ) and California Line Source Dispersion model (CALINE4, NO x , PM 2.5 ) for 57,589 females from the Multiethnic Cohort, residing largely in Los Angeles County from recruitment (1993-1996) through 2010. Cox proportional hazards models were used to examine the associations between time-varying air pollution and breast cancer incidence adjusting for confounding factors. Stratified analyses were conducted by race/ethnicity and distance to major roads. Among all women, breast cancer risk was positively but not significantly associated with NO x (per 50 parts per billion [ppb]) and NO 2 (per 20 ppb) determined by kriging and LUR and with PM 2.5 and PM 10 (per 10 μg/m 3 ) determined by kriging. However, among women who lived within 500 m of major roads, significantly increased risks were observed with NO x (hazard ratio [HR] = 1.35, 95% confidence interval [95% CI]: 1.02-1.79), NO 2 (HR = 1.44, 95% CI: 1.04-1.99), PM 10 (HR = 1.29, 95% CI: 1.07-1.55) and PM 2.5 (HR = 1.85, 95% CI: 1.15-2.99) determined by kriging and NO x (HR = 1.21, 95% CI:1.01-1.45) and NO 2 (HR = 1.26, 95% CI: 1.00-1.59) determined by LUR. No overall associations were observed with exposures assessed by CALINE4. Subgroup analyses suggested stronger associations of NO x and NO 2 among African Americans and Japanese Americans. Further studies of multiethnic populations to confirm the effects of air pollution, particularly near-roadway exposures, on the risk of breast cancer is warranted., (© 2019 UICC.)

Background: Few studies have evaluated accuracy of self-reported family history of breast and other cancers in racial/ethnic minorities., Methods: We assessed the accuracy of cancer family history reports by women with breast cancer (probands) from the Northern California Breast Cancer Family Registry compared with 2 reference standards: personal cancer history reports by female first-degree relatives and California Cancer Registry records., Results: Probands reported breast cancer in first-degree relatives with high accuracy, but accuracy was lower for other cancers. Sensitivity (percentage correctly identifying relatives with cancer) was 93% [95% confidence interval (CI), 89.5-95.4] when compared with the relatives' self-report of breast cancer as the reference standard and varied little by proband race/ethnicity and other demographic factors, except for marginally lower sensitivity for Hispanic white probands (87.3%; 95% CI, 78.0-93.1; P = 0.07) than non-Hispanic white probands (95.1%; 95% CI, 88.9-98.0). Accuracy was also high when compared with cancer registry records as the reference standard, with a sensitivity of 95.5% (95% CI, 93.4-96.9) for breast cancer, but lower sensitivity for Hispanic white probands (91.2%; 95% CI, 84.4-95.2; P = 0.05) and probands with low English language proficiency (80%; 95% CI, 52.8-93.5; P < 0.01)., Conclusions: Non-Hispanic white, African American, and Asian American probands reported first-degree breast cancer family history with high accuracy, although sensitivity was lower for Hispanic white probands and those with low English language proficiency., Impact: Self-reported family history of breast cancer in first-degree relatives is highly accurate and can be used as a reliable standard when other validation methods are not available., (©2019 American Association for Cancer Research.)

Cutaneous squamous cell cancers (cSCCs) present an under-recognized health issue among non-Hispanic whites, one that is likely to increase as populations age. cSCC risks vary considerably among non-Hispanic whites, and this heterogeneity indicates the need for risk-stratified screening strategies that are guided by patients' personal characteristics and clinical histories. Here we describe cSCCscore, a prediction tool that uses patients' covariates and clinical histories to assign them personal probabilities of developing cSCCs within 3 years after risk assessment. cSCCscore uses a statistical model for the occurrence and timing of a patient's cSCCs, whose parameters we estimated using cohort data from 66,995 patients in the Kaiser Permanente Northern California healthcare system. We found that patients' covariates and histories explained approximately 75% of their interpersonal cSCC risk variation. Using cross-validated performance measures, we also found cSCCscore's predictions to be moderately well calibrated to the patients' observed cSCC incidence. Moreover, cSCCscore discriminated well between patients who subsequently did and did not develop a new primary cSCC within 3 years after risk assignment, with area under the receiver operating characteristic curve of approximately 85%. Thus, cSCCscore can facilitate more informed management of non-Hispanic white patients at cSCC risk. cSCCscore's predictions are available at https://researchapps.github.io/cSCCscore/., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Metabolomics is emerging as an important tool for detecting differences between diseased and non-diseased individuals. However, prospective studies are limited., Methods: We examined the detectability, reliability, and distribution of metabolites measured in pre-diagnostic plasma samples in a pilot study of women enrolled in the Northern California site of the Breast Cancer Family Registry. The study included 45 cases diagnosed with breast cancer at least one year after the blood draw, and 45 controls. Controls were matched on age (within 5 years), family status, BRCA status, and menopausal status. Duplicate samples were included for reliability assessment. We used a liquid chromatography/gas chromatography mass spectrometer platform to measure metabolites. We calculated intraclass correlations (ICCs) among duplicate samples, and coefficients of variation (CVs) across metabolites., Results: Of the 661 named metabolites detected, 338 (51%) were found in all samples, and 490 (74%) in more than 80% of samples. The median ICC between duplicates was 0.96 (25th - 75th percentile: 0.82-0.99). We observed a greater than 20% case-control difference in 24 metabolites (p < 0.05), although these associations were not significant after adjusting for multiple comparisons., Conclusions: These data show that assays are reproducible for many metabolites, there is a minimal laboratory variation for the same sample, and a large between-person variation. Despite small sample size, differences between cases and controls in some metabolites suggest that a well-powered large-scale study is likely to detect biological meaningful differences to provide a better understanding of breast cancer etiology.

We report a genome-wide association study of cutaneous squamous cell carcinoma conducted among non-Hispanic white members of the Kaiser Permanente Northern California health care system. The study includes a genome-wide screen of 61,457 members (6,891 cases and 54,566 controls) genotyped on the Affymetrix Axiom European array and a replication phase involving an independent set of 6,410 additional members (810 cases and 5,600 controls). Combined analysis of screening and replication phases identified 10 loci containing single-nucleotide polymorphisms (SNPs) with P-values < 5 × 10(-8). Six loci contain genes in the pigmentation pathway; SNPs at these loci appear to modulate squamous cell carcinoma risk independently of the pigmentation phenotypes. Another locus contains HLA class II genes studied in relation to elevated squamous cell carcinoma risk following immunosuppression. SNPs at the remaining three loci include an intronic SNP in FOXP1 at locus 3p13, an intergenic SNP at 3q28 near TP63, and an intergenic SNP at 9p22 near BNC2. These findings provide insights into the genetic factors accounting for inherited squamous cell carcinoma susceptibility., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The contribution of family history to cutaneous squamous cell carcinoma (SCC) risk has not been systematically quantified., Objective: To examine the association between self-reported family history of skin cancer and SCC risk., Methods and Materials: Cases (n = 415) with a pathology-verified SCC and 415 age-, gender-, and race-matched controls were identified within a large integrated health care delivery system. Family history and skin cancer risk factors were ascertained by survey. Odds ratios (ORs) for associations of SCC with family history of skin cancer were estimated using conditional logistic regression adjusted for environmental and innate SCC risk factors., Results: Any known family history of skin cancer was associated with a four-fold higher risk of SCC, adjusting for known environmental and innate SCC risk factors (OR, 4.0; confidence interval [CI]: 2.5-6.5). An unknown family history of skin cancer showed similar risk for SCC (OR, 3.9; CI: 2.4-6.5). In models including skin cancer type, the strongest association was for family history of basal cell carcinoma (OR, 9.8; CI: 2.6-36.8) and for multiple skin cancer types (OR, 10.5; CI: 3.7-29.6)., Conclusion: Family history of skin cancer is an important independent risk factor for cutaneous SCCs.

Few studies have considered the joint association of body mass index (BMI) and physical activity, two modifiable factors, with all-cause mortality after breast cancer diagnosis. Women diagnosed with invasive breast cancer (n = 4,153) between 1991 and 2000 were enrolled in the Breast Cancer Family Registry through population-based sampling in Northern California, USA; Ontario, Canada; and Melbourne and Sydney, Australia. During a median follow-up of 7.8 years, 725 deaths occurred. Baseline questionnaires assessed moderate and vigorous recreational physical activity and BMI prior to diagnosis. Associations with all-cause mortality were assessed using Cox proportional hazards regression, adjusting for established prognostic factors. Compared with no physical activity, any recreational activity during the 3 years prior to diagnosis was associated with a 34% lower risk of death [hazard ratio (HR) = 0.66, 95% confidence interval (CI): 0.51-0.85] for women with estrogen receptor (ER)-positive tumors, but not those with ER-negative tumors; this association did not appear to differ by race/ethnicity or BMI. Lifetime physical activity was not associated with all-cause mortality. BMI was positively associated with all-cause mortality for women diagnosed at age > or =50 years with ER-positive tumors (compared with normal-weight women, HR for overweight = 1.39, 95% CI: 0.90-2.15; HR for obese = 1.77, 95% CI: 1.11-2.82). BMI associations did not appear to differ by race/ethnicity. Our findings suggest that physical activity and BMI exert independent effects on overall mortality after breast cancer.

Purpose: Patients with early-onset breast and/or ovarian cancer frequently wish to know if they inherited a mutation in one of the cancer susceptibility genes, BRCA1 or BRCA2. Accurate carrier prediction models are needed to target costly testing. Two widely used models, BRCAPRO and BOADICEA, were developed using data from non-Hispanic Whites (NHW), but their accuracies have not been evaluated in other racial/ethnic populations., Methods: We evaluated the BRCAPRO and BOADICEA models in a population-based series of African American, Hispanic, and NHW breast cancer patients tested for BRCA1 and BRCA2 mutations. We assessed model calibration by evaluating observed versus predicted mutations and attribute diagrams, and model discrimination using areas under the receiver operating characteristic curves., Results: Both models were well-calibrated within each racial/ethnic group, with some exceptions. BOADICEA overpredicted mutations in African Americans and older NHWs, and BRCAPRO underpredicted in Hispanics. In all racial/ethnic groups, the models overpredicted in cases whose personal and family histories indicated >80% probability of carriage. The two models showed similar discrimination in each racial/ethnic group, discriminating least well in Hispanics. For example, BRCAPRO's areas under the receiver operating characteristic curves were 83% (95% confidence interval, 63-93%) for NHWs, compared with 74% (59-85%) for African Americans and 58% (45-70%) for Hispanics., Conclusions: The poor performance of the model for Hispanics may be due to model misspecification in this racial/ethnic group. However, it may also reflect racial/ethnic differences in the distributions of personal and family histories among breast cancer cases in the Northern California population.

Context: Information on the prevalence of pathogenic BRCA1 mutation carriers in racial/ethnic minority populations is limited., Objective: To estimate BRCA1 carrier prevalence in Hispanic, African American, and Asian American female breast cancer patients compared with non-Hispanic white patients with and without Ashkenazi Jewish ancestry., Design, Setting, and Participants: We estimated race/ethnicity-specific prevalence of BRCA1 in a population-based, multiethnic series of female breast cancer patients younger than 65 years at diagnosis who were enrolled at the Northern California site of the Breast Cancer Family Registry during the period 1996-2005. Race/ethnicity and religious ancestry were based on self-report. Weighted estimates of prevalence and 95% confidence intervals (CIs) were based on Horvitz-Thompson estimating equations., Main Outcome Measure: Estimates of BRCA1 prevalence., Results: Estimates of BRCA1 prevalence were 3.5% (95% CI, 2.1%-5.8%) in Hispanic patients (n = 393), 1.3% (95% CI, 0.6%-2.6%) in African American patients (n = 341), and 0.5% (95% CI, 0.1%-2.0%) in Asian American patients (n = 444), compared with 8.3% (95% CI, 3.1%-20.1%) in Ashkenazi Jewish patients (n = 41) and 2.2% (95% CI, 0.7%-6.9%) in other non-Hispanic white patients (n = 508). Prevalence was particularly high in young (<35 years) African American patients (5/30 patients [16.7%]; 95% CI, 7.1%-34.3%). 185delAG was the most common mutation in Hispanics, found in 5 of 21 carriers (24%)., Conclusions: Among African American, Asian American, and Hispanic patients in the Northern California Breast Cancer Family Registry, the prevalence of BRCA1 mutation carriers was highest in Hispanics and lowest in Asian Americans. The higher carrier prevalence in Hispanics may reflect the presence of unrecognized Jewish ancestry in this population.

CHEK2, a serine-threonine kinase, is activated in response to agents, such as ionizing radiation, which induce DNA double-strand breaks. Activation of CHEK2 can result in cell cycle checkpoint arrest or apoptosis. One specific variant, CHEK2*1100delC, has been associated with an increased risk of breast cancer. In this population-based study, we screened 2,311 female breast cancer cases and 496 general population controls enrolled in the Ontario and Northern California Breast Cancer Family Registries for this variant (all controls were Canadian). Overall, 30 cases and one control carried the 1100delC allele. In Ontario, the weighted mutation carrier frequency among cases and controls was 1.34% and 0.20%, respectively [odds ratio (OR), 6.65; 95% confidence interval (95% CI), 2.37-18.68]. In California, the weighted population mutation carrier frequency in cases was 0.40%. Across all cases, 1 of 524 non-Caucasians (0.19%) and 29 of 1,775 Caucasians (1.63%) were mutation carriers (OR, 0.12; 95% CI, 0.02-0.89). Among Caucasian cases >45 years age at diagnosis, carrier status was associated with history of benign breast disease (OR, 3.18; 95% CI, 1.30-7.80) and exposure to diagnostic ionizing radiation (excluding mammography; OR, 3.21; 95% CI, 1.13-9.14); compared with women without exposure to ionizing radiation, the association was strongest among women exposed >15 years before diagnosis (OR, 4.28; 95% CI, 1.50-12.20) and among those who received two or more chest X-rays (OR, 3.63; 95% CI, 1.25-10.52). These data supporting the biological relevance of CHEK2 in breast carcinogenesis suggest that further studies examining the joint roles of CHEK2*1100delC carrier status and radiation exposure may be warranted.

Ovarian cysts of several types are common in women of reproductive age. Their etiology is not well understood but is likely related to perturbations in the hypothalamic-pituitary-gonadal axis. The relationship of ovarian cysts to breast cancer risk is not known, although a negative association with polycystic ovarian syndrome has been reported. Incident, invasive female breast cancer cases, population-based controls and unaffected sisters of cases were studied from 3 countries participating in the Breast Cancer Family Registry: Melbourne and Sydney, Australia; the San Francisco Bay Area, USA; and Ontario, Canada. Using the same questionnaire, information was collected on self-reported history of ovarian cysts and other risk factors. Analyses were based on 3,049 cases, 2,344 population controls and 1,934 sister controls from all sites combined. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using both unconditional and conditional logistic regression using an offset term to account for sampling fractions at 2 of the sites. A significantly reduced risk of breast cancer was observed for women reporting a history of ovarian cysts (OR = 0.70, 95% CI 0.59-0.82, among all cases and all controls). This risk estimate was similar regardless of control group used, within all 3 sites and in both premenopausal and postmenopausal women (ORs ranging from 0.68-0.75, all 95% CI excluded 1.00). A self-reported history of ovarian cysts was strongly and consistently associated with a reduced risk of breast cancer. Further study of ovarian cysts may increase our understanding of hormonal and other mechanisms of breast cancer etiology., (Copyright 2005 Wiley-Liss, Inc.)

Data from several countries indicate that 1% to 2% of Ashkenazi Jews carry a pathogenic ancestral mutation of the tumor suppressor gene BRCA1. However, the prevalence of BRCA1 mutations among non-Ashkenazi Whites is uncertain. We estimated mutation carrier prevalence in U.S. non-Hispanic Whites, specific for Ashkenazi status, using data from two population-based series of San Francisco Bay Area patients with invasive cancers of the breast or ovary, and data on breast and ovarian cancer risks in Ashkenazi and non-Ashkenazi carriers. Assuming that 90% of the BRCA1 mutations were detected, we estimate a carrier prevalence of 0.24% (95% confidence interval, 0.15-0.39%) in non-Ashkenazi Whites, and 1.2% (95% confidence interval, 0.5-2.6%) in Ashkenazim. When combined with U.S. White census counts, these prevalence estimates suggest that approximately 550,513 U.S. Whites (506,206 non-Ashkenazim and 44,307 Ashkenazim) carry germ line BRCA1 mutations. These estimates may be useful in guiding resource allocation for genetic testing and genetic counseling and in planning preventive interventions.

Objectives: We evaluated the effects of socioeconomic status and comorbidity on stage of disease and survival among 1509 population-based prostate cancer patients., Methods: We applied logistic regression and Cox proportional hazards regression to data from Whites, African Americans, and Asian Americans who were diagnosed from 1987 to 1991., Results: Patients with existing comorbid conditions were less likely than those without these conditions to be diagnosed with advanced cancer. Compared with Whites, African Americans (odds ratio [OR] = 1.5; 95% confidence interval [CI] = 1.1, 2.2) and foreign-born Asian Americans (OR = 1.6; 95% CI = 1.0, 2.4) were more likely to be diagnosed with advanced cancer. Among men with localized disease, prostate cancer death rates were higher for African Americans than for Whites (death rate ratio = 2.3; 95% CI = 1.2, 4.7)., Conclusions: These findings support the need for further investigation of factors that affect access to and use of health care among African Americans and Asian Americans.

Background: African-American ovarian cancer patients present with more advanced disease and have poorer survival than do white patients., Methods: To determine whether these differences occur among African-American and white patients who have equal access to medical care, we analyzed ovarian cancer patient characteristics separately for 1,587 members of the Kaiser Permanente Medical Plan of Northern California and 5,757 non-members., Results: The distributions of disease stage at diagnosis were similar among African-American and white patients, both in the Kaiser plan and elsewhere. However, ovarian cancer death rates, adjusted for disease stage and age at diagnosis and for histology, were higher for African-American patients compared with white patients, regardless of Kaiser membership status. The death rate ratios for African-Americans compared with whites were 1.32 (95% CI = 1.02-1.70) for Kaiser members and 1.20 (95% CI = 1.04-1.40) for Kaiser non-members., Conclusion: Further research within an equal-access care system is needed to evaluate other important factors such as specialty of surgeon, extent of residual tumor after surgery, chemotherapy treatment, and postoperative management to determine whether these factors are contributing to the differences in survival between African-American and white ovarian cancer patients.