Enrollment and biospecimen collection in a multiethnic family cohort: the Northern California site of the Breast Cancer Family Registry.

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.

Novel colon cancer susceptibility variants identified from a genome-wide association study in African Americans.

Genome-wide association studies (GWAS) in ethnic/racial minority populations can help to fine-map previously identified risk regions or discover new risk loci because of the genetic diversity in these populations. We conducted a GWAS of colorectal cancer (CRC) in 6,597 African Americans (1,894 cases and 4,703 controls) (Stage 1) and followed up the most promising markers in a replication set of 2,041 participants of African descent (891 cases and 1,150 controls) (Stage 2). We identified a novel variant, rs56848936 in the gene SYMPK at 19q13.3, associated with colon cancer risk (odds ratio 0.61 for the risk allele G, p = 2.4 × 10-8 ). The frequency of the G allele was 0.06 in African Americans, compared to <0.01 in Europeans, Asians and Amerindians in the 1000 Genomes project. In addition, a variant previously identified through fine-mapping in this GWAS in the region 19q13.1, rs7252505, was confirmed to be more strongly associated with CRC in the African American replication set than the variant originally reported in Europeans (rs10411210). The association between rs7252505 and CRC was of borderline significance (p = 0.05) in a Hispanic population GWAS with 1,611 CRC cases and 4,330 controls. With the three datasets combined, the odds ratio was 0.84 for the risk allele A (95% confidence interval 0.79-0.89, p = 3.7 × 10-8 ). This study further highlights the importance of conducting GWAS studies in diverse ancestry populations.

Validity of Race, Ethnicity, and National Origin in Population-based Cancer Registries and Rapid Case Ascertainment Enhanced With a Spanish Surname List.

BACKGROUND: Accurate information regarding race, ethnicity, and national origins is critical for identifying disparities in the cancer burden. OBJECTIVES: To examine the use of a Spanish surname list to improve the quality of race-related information obtained from rapid case ascertainment (RCA) and to estimate the accuracy of race-related information obtained from cancer registry records collected by routine reporting. SUBJECTS: Self-reported survey responses of 3954 participants from California enrolled in the Cancer Care Outcomes Research and Surveillance Consortium. MEASURES: Sensitivity, specificity, positive predictive value, and percent agreement. We used logistic regression to identify predictors of underreporting and overreporting of a race/ethnicity. RESULTS: Use of the Spanish surname list increased the sensitivity of RCA for Latino ethnicity from 37% to 83%. Sensitivity for cancer registry records collected by routine reporting was ≥95% for whites, blacks, and Asians, and specificity was high for all groups (86%-100%). However, patterns of misclassification by race/ethnicity were found that could lead to biased cancer statistics for specific race/ethnicities. Discordance between self-reported and registry-reported race/ethnicity was more likely for women, Latinos, and Asians. CONCLUSIONS: Methods to improve race and ethnicity data, such as using Spanish surnames in RCA and instituting data collection guidelines for hospitals, are needed to ensure minorities are accurately represented in clinical and epidemiological research.

Fine-mapping of genome-wide association study-identified risk loci for colorectal cancer in African Americans.

Genome-wide association studies of colorectal cancer (CRC) in Europeans and Asians have identified 21 risk susceptibility regions [29 index single-nucleotide polymorphisms (SNPs)]. Characterizing these risk regions in diverse racial groups with different linkage disequilibrium (LD) structure can help localize causal variants. We examined associations between CRC and all 29 index SNPs in 6597 African Americans (1894 cases and 4703 controls). Nine SNPs in eight regions (5q31.1, 6q26-q27, 8q23.3, 8q24.21, 11q13.4, 15q13.3, 18q21.1 and 20p12.3) formally replicated in our data with one-sided P-values <0.05 and the same risk directions as reported previously. We performed fine-mapping of the 21 risk regions (including 250 kb on both sides of the index SNPs) using genotyped and imputed markers at the density of the 1000 Genomes Project to search for additional or more predictive risk markers. Among the SNPs correlated with the index variants, two markers, rs12759486 (or rs7547751, a putative functional variant in perfect LD with it) in 1q41 and rs7252505 in 19q13.1, were more strongly and statistically significantly associated with CRC (P < 0.0006). The average per allele risk was improved using the replicated index variants and the two new markers (odds ratio = 1.14, P = 6.5 × 10(-16)) in African Americans, compared with using all index SNPs (odds ratio = 1.07, P = 3.4 × 10(-10)). The contribution of the two new risk SNPs to CRC heritability was estimated to be 1.5% in African Americans. This study highlights the importance of fine-mapping in diverse populations.

Racial/ethnic disparities in knowledge about one's breast cancer characteristics.

BACKGROUND: Understanding tumor characteristics is likely important, but little is known about breast cancer patients' knowledge of their own disease. The authors assessed women's knowledge about their tumor characteristics, whether racial/ethnic disparities in knowledge exist, and whether education and health literacy influence associations. METHODS: A population-based cohort of women in Northern California with stage 0 through III breast cancers diagnosed from 2010 to 2011 (participation rate 68.5%) was surveyed. Among 500 respondents (222 non-Hispanic white women, 142 non-Hispanic black women, and 136 Hispanic women), racial/ethnic differences in knowledge about tumor characteristics (estrogen receptor [ER] status, human epidermal growth factor receptor 2 [HER2] status, stage, grade) and correctness of tumor information (with California Cancer Registry data for confirmation) were examined. Multivariate logistic regression was used to assess the probability of: 1) knowing tumor stage, receptor status, and grade; and 2) correctly answering questions about tumor information by race/ethnicity. The impact of education and health literacy on findings was examined in sequential models. RESULTS: Overall, 32% to 82% of women reported knowing each of the 4 tumor characteristics of interest, and 20% to 58% correctly reported these characteristics. After adjustment, black and Hispanic women were less likely than white women to know and have correct responses for stage, ER status, and HER2 status (all P<.05). Education and health literacy were significantly associated with knowing and having correct information about some characteristics, but these variables did not eliminate most of the racial/ethnic differences observed. CONCLUSIONS: Patient's knowledge about their own breast cancer was generally poor, particularly for minority women. Further study of how this knowledge may impact receipt of care and outcomes is warranted.

Effect of Massachusetts health insurance reform on mammography use and breast cancer stage at diagnosis.

BACKGROUND: Massachusetts law requires all residents to maintain a minimum level of health insurance, and rates of uninsurance in that state decreased from 6.4% in 2006 to 1.9% in 2010. The authors of this report assessed whether health insurance expansion was associated with use of mammography and earlier stage at breast cancer diagnosis. METHODS: By using a prereform/postreform design with a concurrent control (California), mammography rates in the last year were assessed using the Behavioral Risk Factor Surveillance System survey and the diagnosis of stage I (vs II/III/IV) breast cancers based on cancer registry data among women ages 41 to 64. Propensity score analyses were used to compare California women who were most similar to women in Massachusetts with Massachusetts women. RESULTS: Among propensity-weighted cohorts, adjusted mammography rates in Massachusetts were 69.2% in 2006, 69.5% in 2008, and 69.0% in 2010. In California, the rates were 59% in 2006, 60.3% in 2008, and 56.2% in 2010 (P = .89 for interaction by state for 2010 vs 2006). Among propensity-weighted cohorts, adjusted rates of diagnosis with stage I cancers were 52.2% in 2006, 53.5% in 2007, and 52.4% in 2008 in Massachusetts versus 46.4% in 2006, 46.3% in 2007, and 45.7% in 2008 in California (P = .58 for interaction by state for 2010 vs 2006). CONCLUSIONS: Health insurance reform in Massachusetts was not associated with increased rates of mammography or earlier stage at diagnosis compared with California, possibly because of insurance and mammography rates that already were high. Additional research is needed to assess the impact of insurance expansions in other populations, especially those with higher uninsurance rates.

Chemotherapy use and patient treatment preferences in advanced colorectal cancer: a prospective cohort study.

BACKGROUND: The objective of this study was to determine how patient preferences guide the course of palliative chemotherapy for advanced colorectal cancer. METHODS: Eligible patients with metastatic colorectal cancer (mCRC) were enrolled nationwide in a prospective, population-based cohort study. Data were obtained through medical record abstraction and patient surveys. Logistic regression analysis was used to evaluate patient characteristics associated with visiting medical oncology and receiving chemotherapy and patient characteristics, beliefs, and preferences associated with receiving >1 line of chemotherapy and receiving combination chemotherapy. RESULTS: Among 702 patients with mCRC, 91% consulted a medical oncologist; and among those, 82% received chemotherapy. Patients ages 65 to 75 years and aged ≥75 years were less likely to visit an oncologist, as were patients who were too sick to complete their own survey. In adjusted analyses, patients aged ≥75 years who had moderate or severe comorbidity were less likely to receive chemotherapy, as were patients who were too sick to complete their own survey. Patients received chemotherapy even if they believed that chemotherapy would not extend their life (90%) or that chemotherapy would not likely help with cancer-related problems (89%), or patients preferred treatment focusing on comfort even if it meant not living as long (90%). Older patients were less likely to receive combination first-line therapy. Patient preferences and beliefs were not associated with receipt of >1 line of chemotherapy or combination chemotherapy. CONCLUSIONS: The majority of patients received chemotherapy even if they expressed negative or marginal preferences or beliefs regarding chemotherapy. Patient preferences and beliefs were not associated with the intensity or number of chemotherapy regimens.

Changes in health status among aging survivors of pediatric upper and lower extremity sarcoma: a report from the childhood cancer survivor study.

OBJECTIVE: To evaluate health status and participation restrictions in survivors of childhood extremity sarcomas. DESIGN: Members of the Childhood Cancer Survivor Study cohort with extremity sarcomas who completed questionnaires in 1995, 2003, or 2007 were included. SETTING: Cohort study of survivors of extremity sarcomas. PARTICIPANTS: Childhood extremity sarcoma survivors (N=1094; median age at diagnosis, 13y (range, 0-20y); current age, 33y (range, 10-53y); 49% male; 87.5% white; 75% had lower extremity tumors) who received their diagnosis and treatment between 1970 and 1986. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Prevalence rates for poor health status in 6 domains and 5 suboptimal social participation categories were compared by tumor location and treatment exposure with generalized estimating equations adjusted for demographic/personal factors and time/age. RESULTS: In adjusted models, when compared with upper extremity survivors, lower extremity survivors had an increased risk of activity limitations but a lower risk of not completing college. Compared with those who did not have surgery, those with limb-sparing (LS) and upper extremity amputations (UEAs) were 1.6 times more likely to report functional impairment, while those with an above-the-knee amputation (AKA) were 1.9 times more likely to report functional impairment. Survivors treated with LS were 1.5 times more likely to report activity limitations. Survivors undergoing LS were more likely to report inactivity, incomes <$20,000, unemployment, and no college degree. Those with UEAs more likely reported inactivity, unmarried status, and no college degree. Those with AKA more likely reported no college degree. Treatment with abdominal irradiation was associated with an increased risk of poor mental health, functional impairment, and activity limitation. CONCLUSIONS: Treatment of lower extremity sarcomas is associated with a 50% increased risk for activity limitations; upper extremity survivors are at a 10% higher risk for not completing college. The type of local control influences health status and participation restrictions. Both of these outcomes decline with age.

Risk factors for uncommon histologic subtypes of breast cancer using centralized pathology review in the Breast Cancer Family Registry.

Epidemiologic studies of histologic types of breast cancer including mucinous, medullary, and tubular carcinomas have primarily relied on International Classification of Diseases-Oncology (ICD-O) codes assigned by local pathologists to define histology. Using data from the Breast Cancer Family Registry (BCFR), we compared histologic agreement between centralized BCFR pathology review and ICD-O codes available from local tumor registries among 3,260 breast cancer cases. Agreement was low to moderate for less common histologies; for example, only 55 and 26 % of cases classified as mucinous and medullary, respectively, by centralized review were similarly classified using ICD-O coding. We then evaluated risk factors for each histologic subtype by comparing each histologic case group defined by centralized review with a common set of 2,997 population-based controls using polytomous logistic regression. Parity [odds ratio (OR) = 0.4, 95 % confidence interval (95 % CI): 0.2-0.9, for parous vs. nulliparous], age at menarche (OR = 0.5, 95 % CI: 0.3-0.9, for age ≥13 vs. ≤11), and use of oral contraceptives (OCs) (OR = 0.5, 95 % CI: 0.2-0.8, OC use >5 years vs. never) were associated with mucinous carcinoma (N = 92 cases). Body mass index (BMI) (OR = 1.05, 95 % CI: 1.0-1.1, per unit of BMI) and high parity (OR = 2.6, 95 % CI: 1.1-6.0 for ≥3 live births vs. nulliparous) were associated with medullary carcinoma (N = 90 cases). We did not find any associations between breast cancer risk factors and tubular carcinoma (N = 86 cases). Relative risk estimates from analyses using ICD-O classifications of histology, rather than centralized review, resulted in attenuated, and/or more imprecise, associations. These findings suggest risk factor heterogeneity across breast cancer tumor histologies, and demonstrate the value of centralized pathology review for classifying rarer tumor types.

Accuracy of BRCA1/2 mutation prediction models for different ethnicities and genders: experience in a southern Chinese cohort.

BACKGROUND: BRCA1/2 mutation prediction models (BRCAPRO, Myriad II, Couch, Shattuck-Eidens, BOADICEA) are well established in western cohorts to estimate the probability of BRCA1/2 mutations. Results are conflicting in Asian populations. Most studies did not account for gender-specific prediction. We evaluated the performance of these models in a Chinese cohort, including males, before BRCA1/2 mutation testing. METHODS: The five risk models were used to calculate the probability of BRCA mutations in probands with breast and ovarian cancers; 267 were non-BRCA mutation carriers (247 females and 20 males) and 43 were BRCA mutation carriers (38 females and 5 males). RESULTS: Mean BRCA prediction scores for all models were statistically better for carriers than noncarriers for females but not for males. BRCAPRO overestimated the numbers of female BRCA1/2 mutation carriers at thresholds ≥20% but underestimated if <20%. BRCAPRO and BOADICEA underestimated the number of male BRCA1/2 mutation carriers whilst Myriad II underestimated the number of both male and female carriers. In females, BRCAPRO showed similar discrimination, as measured by the area under the receiver operator characteristic curve (AUC) for BRCA1/2 combined mutation prediction to BOADICEA, but performed better than BOADICEA in BRCA1 mutation prediction (AUC 93% vs. 87%). BOADICEA had the best discrimination for BRCA1/2 combined mutation prediction (AUC 87%) in males. CONCLUSIONS: The variation in model performance underscores the need for research on larger Asian cohorts as prediction models, and the possible need for customizing these models for different ethnic groups and genders.

The association of body mass index with mortality in the California Teachers Study.

Although underweight and obesity have been associated with increased risk of mortality, it remains unclear whether the associations differ by hormone therapy (HT) use and smoking. The authors examined the relationship between body mass index (BMI) and mortality within the California Teachers Study (CTS), specifically considering the impact of HT and smoking. The authors examined the associations of underweight and obesity with risks of all-cause and cause-specific mortality, among 115,433 women participating in the CTS, and specifically examined whether HT use or smoking modifies the effects of obesity. Multivariable Cox proportional hazards regression provided estimates of relative risks (RRs) and 95% confidence intervals (CIs). During follow up, 10,574 deaths occurred. All-cause mortality was increased for underweight (BMI <18.5; adjusted RR = 1.33, 95% CI = 1.20-1.47) and obese participants (BMI ≥ 30: RR = 1.27, 95% CI = 1.19-1.37) relative to BMI of 18.5-24.9). Respiratory disease mortality was increased for underweight and obese participants. Death from any cancer, and breast cancer specifically, and cardiovascular disease was observed only for obese participants. The obesity and mortality association remained after stratification on HT and smoking. Obese participants remained at greater risk for mortality after stratification on menopausal HT and smoking. Obesity was associated with increased all-cause mortality, as well as death from any cancer (including breast), and cardiovascular and respiratory diseases. These findings help to identify groups at risk for BMI-related poor health outcomes.

Dietary phytocompounds and risk of lymphoid malignancies in the California Teachers Study cohort.

OBJECTIVE: We examined whether dietary intake of isoflavones, lignans, isothiocyanates, antioxidants, or specific foods rich in these compounds is associated with reduced risk of B-cell non-Hodgkin lymphoma (NHL), multiple myeloma (MM), or Hodgkin lymphoma (HL) in a large, prospective cohort of women. METHODS: Between 1995-1996 and 31 December 2007, among 110,215 eligible members of the California Teachers Study cohort, 536 women developed incident B-cell NHL, 104 developed MM, and 34 developed HL. Cox proportional hazards regression, with age as the time scale, was used to estimate adjusted rate ratios (RRs) with 95% confidence intervals (CIs) for risk of lymphoid malignancies. RESULTS: Weak inverse associations with risk of diffuse large B-cell lymphoma were observed for isothiocyanates (RR for ≥12.1 vs. <2.7 mcM/day = 0.67, 95% CI: 0.43-1.05) and an antioxidant index measuring hydroxyl radical absorbance capacity (RR for ≥2.2 vs. <0.9 µM Trolox equiv/g/day = 0.68, 95% CI: 0.42-1.10; p (trend) = 0.08). Risk of other NHL subtypes, overall B-cell NHL, MM, or HL was not generally associated with dietary intake of isoflavones, lignans, isothiocyanates, antioxidants, or major food sources of these compounds. CONCLUSIONS: Isoflavones, lignans, isothiocyanates, and antioxidant compounds are not associated with risk of most B-cell malignancies, but some phytocompounds may decrease the risk of selected subtypes.

Early dissemination of bevacizumab for advanced colorectal cancer: a prospective cohort study.

BACKGROUND: We describe early dissemination patterns for first-line bevacizumab given for metastatic colorectal cancer treatment. METHODS: We analyzed patient surveys and medical records for a population-based cohort with metastatic colorectal cancer treated in multiple regions and health systems in the United States (US). Eligible patients were diagnosed with metastatic colorectal cancer and initiated first-line chemotherapy after US Food & Drug Administration (FDA) bevacizumab approval in February 2004. First-line bevacizumab therapy was defined as receiving bevacizumab within 8 weeks of starting chemotherapy for metastatic colorectal cancer. We evaluated factors associated with first-line bevacizumab treatment using logistic regression. RESULTS: Among 355 patients, 31% received first-line bevacizumab in the two years after FDA approval, including 26% of men, 41% of women, and 16% of those ≥ 75 years. Use rose sharply within 6 months after FDA approval, then plateaued. 20% of patients received bevacizumab in combination with irinotecan; 53% received it with oxaliplatin. Men were less likely than women to receive bevacizumab (adjusted OR 0.55; 95% CI 0.32-0.93; p = 0.026). Patients ≥ 75 years were less likely to receive bevacizumab than patients < 55 years (adjusted OR 0.13; 95% CI 0.04-0.46; p = 0.001). CONCLUSIONS: One-third of eligible metastatic colorectal cancer patients received first-line bevacizumab shortly after FDA approval. Most patients did not receive bevacizumab as part of the regimen used in the pivotal study leading to FDA approval.

Spiritual well-being and health-related quality of life in colorectal cancer: a multi-site examination of the role of personal meaning.

PURPOSE: Individuals diagnosed and treated for cancer often report high levels of distress, continuing even after successful treatment. Spiritual well-being (SpWB) has been identified as an important factor associated with positive health outcomes. This study had two aims: (1) examine the associations between SpWB (faith and meaning/peace) and health-related quality of life (HRQL) outcomes and (2) examine competing hypotheses of whether the relationship among distress, SpWB, and HRQL is better explained by a stress-buffering (i.e., interaction) or a direct (main effects) model. METHODS: Study 1 consisted of 258 colorectal cancer survivors (57% men) recruited from comprehensive cancer centers in metropolitan areas (age, M=61; months post-diagnosis, M=17). Study 2 consisted of 568 colorectal cancer survivors (49% men) recruited from a regional cancer registry (age, M=67; months post-diagnosis, M=19). Participants completed measures of SpWB (functional assessment of chronic illness therapy-spiritual well-being (FACIT-Sp)) and HRQL (functional assessment of cancer therapy-colorectal) in both studies. Measures of general distress (profile of mood states-short form) and cancer-specific distress were also completed in study 1 and study 2, respectively. RESULTS: After controlling for demographic and clinical variables, faith and meaning/peace were positively associated with HRQL. However, meaning/peace emerged as a more robust predictor of HRQL outcomes than faith. Planned analyses supported a direct rather than stress-buffering effect of meaning/peace. CONCLUSIONS: This study provides further evidence of the importance of SpWB, particularly meaning/peace, to HRQL for people with colorectal cancer. Future studies of SpWB and cancer should examine domains of the FACIT-Sp separately and explore the viability of meaning-based interventions for cancer survivors.

Alcohol consumption over time and risk of lymphoid malignancies in the California Teachers Study cohort.

Several previous studies found inverse associations between alcohol consumption and risk of non-Hodgkin lymphoma (NHL) and multiple myeloma. However, most studies were retrospective, and few distinguished former drinkers or infrequent drinkers from consistent nondrinkers. Therefore, the authors investigated whether history of alcohol drinking affected risks of NHL and multiple myeloma among 102,721 eligible women in the California Teachers Study, a prospective cohort study in which 496 women were diagnosed with B-cell NHL and 101 were diagnosed with multiple myeloma between 1995-1996 and December 31, 2007. Incidence rate ratios and 95% confidence intervals were estimated using Cox proportional hazards regression. Risk of all types of B-cell NHL combined or multiple myeloma was not associated with self-reported past consumption of alcohol, beer, wine, or liquor at ages 18-22 years, at ages 30-35 years, or during the year before baseline. NHL subtypes were inconsistently associated with alcohol intake. However, women who were former alcohol drinkers at baseline were at elevated risk of overall B-cell NHL (rate ratio = 1.46, 95% confidence interval: 1.08, 1.97) and follicular lymphoma (rate ratio = 1.81, 95% confidence interval: 1.00, 3.28). The higher risk among former drinkers emphasizes the importance of classifying both current and past alcohol consumption and suggests that factors related to quitting drinking, rather than alcohol itself, may increase B-cell NHL risk.

Parents' ages at birth and risk of adult-onset hematologic malignancies among female teachers in California.

Although advanced parental age at one's birth has been associated with increased risk of breast and prostate cancers, few studies have examined its effect on adult-onset sporadic hematologic malignancies. The authors examined the association of parents' ages at women's births with risk of hematologic malignancies among 110,999 eligible women aged 22-84 years recruited into the prospective California Teachers Study. Between 1995 and 2007, 819 women without a family history of hematologic malignancies were diagnosed with incident lymphoma, leukemia (primarily acute myeloid leukemia), or multiple myeloma. Multivariable-adjusted Cox proportional hazards models provided estimates of relative risks and 95% confidence intervals. Paternal age was positively associated with non-Hodgkin lymphoma after adjustment for race and birth order (relative risk for age > or =40 vs. <25 years = 1.51, 95% confidence interval: 1.08, 2.13; P-trend = 0.01). Further adjustment for maternal age did not materially alter the association. By contrast, the elevated non-Hodgkin lymphoma risk associated with advanced maternal age (> or =40 years) became null when paternal age was included in the statistical model. No association was observed for acute myeloid leukemia or multiple myeloma. Advanced paternal age may play a role in non-Hodgkin lymphoma etiology. Potential etiologic mechanisms include de novo gene mutations, aberrant paternal gene imprinting, or telomere/telomerase biology.

Low level alcohol intake, cigarette smoking and risk of breast cancer in Asian-American women.

Studies have shown that breast cancer incidence rates among Asian migrants to the United States approach US incidence rates over several generations, implicating potentially modifiable exposures such as moderate alcohol use that has been linked to excess breast cancer risk in other populations. The goal of this study was to investigate the effect of alcohol intake, primarily low levels, on breast cancer risk in Asian-American women and explore whether smoking and alcohol contributed to the breast cancer incidence rates observed among Asian migrants to the United States. Study subjects in this population-based case-control study included 597 incident cases of breast cancer of Chinese, Japanese, and Filipino ethnicity living in San Francisco-Oakland, Los Angeles, and Oahu, Hawaii, and 966 population controls frequency matched on age, ethnicity, and area of residence. The fraction of smokers and drinkers was significantly higher in women born in Western compared with Eastern countries. However, breast cancer risk was not significantly associated with smoking (odds ratio (OR) = 1.2, 95% confidence interval (95% CI) = 0.9-1.6) or alcohol drinking (OR = 0.9, 95% CI = 0.7-1.1) in this population of low consumers of alcohol (median intake among drinkers in grams per day was 0.48 for cases and 0.40 for controls). These data suggest that low alcohol intake is not related to increased breast cancer risk in Asian-American women and that neither alcohol nor cigarette use contributed to the elevated risks in Asian-American women associated with migration patterns and Westernization.

Hypertension is an independent predictor of survival disparity between African-American and white breast cancer patients.

The objective of this study was to determine whether comorbidity, or pre-existing conditions, can account for some of the disparity in survival between African-American and white breast cancer patients. A historical cohort study was conducted of 416 African-American and 838 white women diagnosed with breast cancer between 1973 and 1986, and followed through 1999 in the Kaiser Permanente Northern California Medical Care Program. Information on comorbidity, tumor characteristics and breast cancer treatment was obtained from medical records, and Surveillance, Epidemiology and End Results, Northern California Cancer Center Registry. Associations between comorbidity and survival were analyzed with multiple Cox proportional hazards regression. Over a mean follow-up of 9 years, African Americans had higher overall crude mortality than whites: 165 (39.7%) versus 279 (33.3%), respectively. When age, race, tumor characteristics and breast cancer treatment were controlled, the presence of hypertension was associated with all cause survival [hazard ratio (HR) = 1.33, 95% confidence intervals (CI) 1.07-1.67] and it accounted for 30% of racial disparity in this outcome. Hypertension-augmented Charlson Comorbidity Index was a significant predictor of survival from all causes (HR = 1.32, 95%CI 1.18-1.49), competing causes (HR = 1.52, 95%CI 1.32-1.76) and breast cancer specific causes (HR = 1.18, 95%CI 1.03-1.35). In conclusion, hypertension has prognostic significance in relation to survival disparity between African-American and white breast cancer patients. If our findings are replicated in contemporary cohorts, it may be necessary to include hypertension in the Charlson Comorbidity Index and other comorbidity measures.

Performance of prediction models for BRCA mutation carriage in three racial/ethnic groups: findings from the Northern California Breast Cancer Family Registry.

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.

Childhood soy intake and breast cancer risk in Asian American women.

INTRODUCTION: Historically, breast cancer incidence has been substantially higher in the United States than in Asia. When Asian women migrate to the United States, their breast cancer risk increases over several generations and approaches that for U.S. Whites. Thus, modifiable factors, such as diet, may be responsible. METHODS: In this population-based case-control study of breast cancer among women of Chinese, Japanese, and Filipino descent, ages 20 to 55 years, and living in San Francisco-Oakland (California), Los Angeles (California) and Oahu (Hawaii), we interviewed 597 cases (70% of those eligible) and 966 controls (75%) about adolescent and adult diet and cultural practices. For subjects with mothers living in the United States (39% of participants), we interviewed mothers of 99 cases (43% of eligible) and 156 controls (40%) about the daughter's childhood exposures. Seventy-three percent of study participants were premenopausal at diagnosis. RESULTS: Comparing highest with lowest tertiles, the multivariate relative risks (95% confidence interval) for childhood, adolescent, and adult soy intake were 0.40 (0.18-0.83; P(trend) = 0.03), 0.80 (0.59-1.08; P(trend) = 0.12), and 0.76 (0.56-1.02; P(trend) = 0.04), respectively. Inverse associations with childhood intake were noted in all three races, all three study sites, and women born in Asia and the United States. Adjustment for measures of westernization attenuated the associations with adolescent and adult soy intake but did not affect the inverse relationship with childhood soy intake. DISCUSSION: Soy intake during childhood, adolescence, and adult life was associated with decreased breast cancer risk, with the strongest, most consistent effect for childhood intake. Soy may be a hormonally related, early-life exposure that influences breast cancer incidence.