Family history of prostate and colorectal cancer and risk of colorectal cancer in the Women's health initiative.

BACKGROUND: Evidence suggests that risk of colorectal and prostate cancer is increased among those with a family history of the same disease, particularly among first-degree relatives. However, the aggregation of colorectal and prostate cancer within families has not been well investigated. METHODS: Analyses were conducted among participants of the Women's Health Initiative (WHI) observational cohort, free of cancer at the baseline examination. Subjects were followed for colorectal cancer through August 31st, 2009. A Cox-proportional hazards regression modeling approach was used to estimate risk of colorectal cancer associated with a family history of prostate cancer, colorectal cancer and both cancers among first-degree relatives of all participants and stratified by race (African American vs. White). RESULTS: Of 75,999 eligible participants, there were 1122 colorectal cancer cases diagnosed over the study period. A family history of prostate cancer alone was not associated with an increase in colorectal cancer risk after adjustment for confounders (aHR =0.94; 95% CI =0.76, 1.15). Separate analysis examining the joint impact, a family history of both colorectal and prostate cancer was associated with an almost 50% increase in colorectal cancer risk (aHR = 1.48; 95% CI = 1.04, 2.10), but similar to those with a family history of colorectal cancer only (95% CI = 1.31; 95% CI = 1.11, 1.54). CONCLUSIONS: Our findings suggest risk of colorectal cancer is increased similarly among women with colorectal cancer only and among those with both colorectal and prostate cancer diagnosed among first-degree family members. Future studies are needed to determine the relative contribution of genes and shared environment to the risk of both cancers.

Mesothelioma in the United States: a Surveillance, Epidemiology, and End Results (SEER)-Medicare investigation of treatment patterns and overall survival.

INTRODUCTION: Mesothelioma is a rare malignancy typically associated with exposure to asbestos and poor survival. The purpose of this investigation was to describe mesothelioma patient characteristics, treatment patterns, and overall survival (OS) utilizing the National Cancer Institute's Surveillance, Epidemiology, and End Results-Medicare database. MATERIALS AND METHODS: Patients in this study were diagnosed with malignant mesothelioma of the pleura or peritoneum between January 1, 2005 and December 31, 2009 with follow-up for survival through December 31, 2010. We examined both patient and tumor characteristics at time of diagnosis and subsequent treatment patterns (surgery, radiation, and chemotherapy). Among patients treated with chemotherapy, we determined chemotherapy regimen and OS by line of therapy. RESULTS: Of the 1,625 patients considered eligible for this investigation, the median age at diagnosis was 78 years. Nearly a third of patients (30%) had surgery as part of their treatment and 45% were given chemotherapy. The median OS was 8 months (range 1-69 months). Among chemotherapy patients, the most commonly (67%) prescribed regimen for first-line therapy was cisplatin or carboplatin (Ca/Ci) combined with pemetrexed (Pe). Among those prescribed Ca/Ci + Pe as first-line therapy, retreatment with Ca/Ci + Pe (28%) or treatment with gemcitabine (30%) were the most common second-line therapies. Median OS for those receiving first-line chemotherapy was 7 months, and among those receiving second-line therapy median OS was extended an additional 5 months. CONCLUSION: Irrespective of surgical resection, mesothelioma patients receiving some form of chemotherapy survived longer than patients who did not, with an additional survival benefit among those patients receiving multimodal treatment.

The HOXB13 G84E Mutation Is Associated with an Increased Risk for Prostate Cancer and Other Malignancies.

BACKGROUND: A rare nonconservative substitution (G84E) in the HOXB13 gene has been shown to be associated with risk of prostate cancer. DNA samples from male patients included in the Mayo Clinic Biobank (MCB) were genotyped to determine the frequency of the G84E mutation and its association with various cancers. METHODS: Subjects were genotyped using a custom TaqMan (Applied Biosystems) assay for G84E (rs138213197). In addition to donating a blood specimen, all MCB participants completed a baseline questionnaire to collect information on medical history and family history of cancer. RESULTS: Forty-nine of 9,012 male patients were carriers of G84E (0.5%). Thirty-one percent (n = 2,595) of participants had been diagnosed with cancer, including 51.1% of G84E carriers compared with just 30.6% of noncarriers (P = 0.004). G84E was most frequently observed among men with prostate cancer compared with men without cancer (P < 0.0001). However, the mutation was also more commonly observed in men with bladder cancer (P = 0.06) and leukemia (P = 0.01). G84E carriers were more likely to have a positive family history of prostate cancer in a first-degree relative compared to noncarriers (36.2% vs. 16.0%, P = 0.0003). CONCLUSIONS: Our study confirms the association between the HOXB13 G84E variant and prostate cancer and suggests a novel association between G84E and leukemia and a suggestive association with bladder cancer. Future investigation is warranted to confirm these associations in order to improve our understanding of the role of germline HOXB13 mutations in human cancer. IMPACT: The associations between HOXB13 and prostate, leukemia, and bladder suggest that this gene is important in carcinogenesis.

Familial clustering of breast and prostate cancer and risk of postmenopausal breast cancer in the Women's Health Initiative Study.

BACKGROUND: Evidence suggests that the risk of breast and prostate cancer is increased among those with a family history of the same disease and particularly among first-degree relatives. However, less is known about the relationship between breast and prostate cancer within families and particularly among minority populations. METHODS: Analyses of participants in the Women's Health Initiative observational cohort who were free of breast cancer at the time of their baseline examination were conducted. Subjects were followed for breast cancer through August 31, 2009. A Cox proportional hazards regression modeling approach was used to estimate the risk of breast cancer associated with a family history of prostate cancer, breast cancer, and both among first-degree relatives. RESULTS: There were 78,171 eligible participants, and 3506 breast cancer cases were diagnosed during the study period. A family history of prostate cancer was associated with a modest increase in breast cancer risk after adjustments for confounders (adjusted hazard ratio [aHR], 1.14; 95% confidence interval [CI], 1.02-1.26). In a separate analysis examining the joint impact of both cancers, a family history of both breast and prostate cancer was associated with a 78% increase in breast cancer risk (aHR, 1.78; 95% CI, 1.45-2.19). Risk estimates associated with a family history of both breast and prostate cancer were higher among African American women (aHR, 2.34; 95% CI, 1.09-5.02) versus white women (aHR, 1.66; 95% CI, 1.33-2.08). CONCLUSIONS: These findings suggest that prostate cancer diagnosed among first-degree family members increases a woman's risk of developing breast cancer. Future studies are needed to determine the relative contributions of genes and a shared environment to the risk for both cancers.

Risk of second primary tumors in men diagnosed with prostate cancer: a population-based cohort study.

BACKGROUND: The survival of men diagnosed with prostate cancer has improved over time, and the current 10-year relative survival rate is 99.7%. The long survival of patients with this common cancer raises questions about the risk of a second primary cancer and the need for continued surveillance. METHODS: A population-based cohort of 441,504 men who were diagnosed with prostate cancer between 1992 and 2010 was identified from Surveillance, Epidemiology and End Results Program (SEER) data (SEER13). The standardized incidence ratio (SIR) was calculated as an estimate of the risk of a second primary malignancy based on the incidence in the general population. RESULTS: Prostate cancer survivors had a lower risk of being diagnosed with another cancer overall compared with the US population (SIR = 0.60; 95% confidence interval, 0.60-0.61). The risks of leukemia and cancers of the oral cavity and pharynx, esophagus, stomach, colon and rectum, liver, gallbladder, pancreas, lung and bronchus, and larynx were significantly lower. Conversely, these patients had a greater risk of bladder, kidney, and endocrine and soft tissue cancers. Men who received treatment with radiation therapy (external-beam radiation therapy) had long-term increases in their risk of bladder cancer (SIR = 1.42) and rectal cancer (SIR = 1.70) risk compared with who did not receive radiation (SIRbladder = 0.76; SIRrectal = 0.74). There were significant racial differences in the risk of being diagnosed with a second primary cancer, and the magnitude and direction of these risks depended on tumor type. CONCLUSIONS: Prostate cancer survivors remain at risk of subsequent malignancies, and race and treatment choice important determinants of long-term risk.

Patterns of care, predictors, and outcomes of chemotherapy in elderly women with early-stage uterine carcinosarcoma: a population-based analysis.

OBJECTIVE: To examine the patterns of care, predictors, and impact of chemotherapy on survival in elderly women diagnosed with early-stage uterine carcinosarcoma. METHODS: The Surveillance, Epidemiology, and End Results (SEER)-Medicare database was used to identify women 65 years or older diagnosed with stage I-II uterine carcinosarcomas from 1991 through 2007. Multivariable logistic regression and Cox-proportional hazards models were used for statistical analysis. RESULTS: A total of 462 women met the eligibility criteria; 374 had stage I, and 88 had stage II uterine carcinosarcomas. There were no appreciable differences over time in the percentages of women administered chemotherapy for early stage uterine carcinosarcoma (14.7% in 1991-1995, 14.9% in 1996-2000, and 17.9% in 2001-2007, P=0.67). On multivariable analysis, the factors positively associated with receipt of chemotherapy were younger age at diagnosis, higher disease stage, residence in the eastern part of the United States, and lack of administration of external beam radiation (P<0.05). In the adjusted Cox-proportional hazards regression models, administration of three or more cycles of chemotherapy did not reduce the risk of death in stage I patients (HR: 1.45, 95% CI: 0.83-2.39) but was associated with non-significant decreased mortality in stage II patients (HR: 0.83, 95% CI: 0.32-1.95). CONCLUSIONS: Approximately 15-18% of elderly patients diagnosed with early-stage uterine carcinosarcoma were treated with chemotherapy. This trend remained stable over time, and chemotherapy was not associated with any significant survival benefit in this patient population.

Prevalence of the HOXB13 G84E prostate cancer risk allele in men treated with radical prostatectomy.

OBJECTIVE: To determine the prevalence and clinical correlates of the G84E mutation in the homeobox transcription factor, or HOXB13, gene using DNA samples from 9559 men with prostate cancer undergoing radical prostatectomy. PATIENTS AND METHODS: DNA samples from men treated with radical prostatectomy at the University of Michigan and John Hopkins University were genotyped for G84E and this was confirmed by Sanger sequencing. The frequency and distribution of this allele was determined according to specific patient characteristics (family history, age at diagnosis, pathological Gleason grade and stage). RESULTS: Of 9559 patients, 128 (1.3%) were heterozygous carriers of G84E. Patients who possessed the variant were more likely to have a family history of prostate cancer than those who did not (46.0 vs 35.4%; P = 0.006). G84E carriers were also more likely to be diagnosed at a younger age than non-carriers (55.2 years vs 58.1 years; P < 0.001). No difference in the proportion of patients diagnosed with high grade or advanced stage tumours according to carrier status was observed. CONCLUSIONS: In the present study, carriers of the rare G84E variant in HOXB13 were both younger at the time of diagnosis and more likely to have a family history of prostate cancer compared with homozygotes for the wild-type allele. No significant differences in allele frequency were detected according to selected clinical characteristics of prostate cancer. Further investigation is required to evaluate the role of HOXB13 in prostate carcinogenesis.

Timing of androgen deprivation therapy use and fracture risk among elderly men with prostate cancer in the United States.

PURPOSE: Fractures are a recognized consequence of androgen deprivation therapy (ADT); however, less is known about the incidence of fracture in relation to the timing of ADT use or the impact of fracture on mortality in men with prostate cancer. METHODS: Using data from the Surveillance, Epidemiology, and End Results-Medicare linked database, we estimated adjusted hazard ratios (aHRs) using time-dependent Cox regression for fracture incidence related to the recency of exposure and dose among prostate cancer patients on gonadotropin-releasing hormone (GnRH) agonists, as well as mortality associated with fractures. RESULTS: In our cohort of 80 844 patients, ADT was associated with an increased rate of fracture in both non-metastatic patients (aHR = 1.34; 95% confidence interval [CI] = 1.29-1.39) and metastatic patients (aHR = 1.51; 95%CI = 1.36-1.67). Fracture rates increased with increasing cumulative GnRH dose but decreased with increasing number of months since last use in each dose category. The mortality rate doubled for men experiencing a fracture after their diagnosis compared with that for men who did not experience a fracture (aHR = 2.05; 95%CI = 1.98-2.12). CONCLUSIONS: ADT in elderly men with prostate cancer increased the incidence of fractures, and the effect appears to diminish with increasing time since the last dose of a GnRH agonist. Experiencing a fracture after the diagnosis of prostate cancer was associated with decreased survival.

Androgen deprivation therapy and cataract incidence among elderly prostate cancer patients in the United States.

PURPOSE: The side-effects associated with androgen deprivation therapy (ADT) include weight gain, dyslipidemia, and insulin resistance. As cataracts have been linked to these metabolic abnormalities, an increased risk of cataract may be another adverse consequence of ADT use. METHODS: Using data from the Surveillance, Epidemiology and End Results-Medicare database, we estimated risk of cataract associated with ADT among 65,852 prostate-cancer patients. ADT treatment was defined as at least one dose of a gonadotropin-releasing hormone agonist or orchiectomy within 6 months after prostate cancer diagnosis. The outcome measure was a first claim of cataract diagnosis identified in Medicare claim files. Cox regression was used to estimate hazard ratios (HR) for the effects of ADT treatment, controlling for confounders. RESULTS: Gonadotropin-releasing hormone agonist use was associated with a modest increase in cataract incidence (HR 1.09, 95% confidence interval 1.06-1.12). Orchiectomy was also associated with an increased risk of cataract among men with no history of cataract prior to prostate cancer diagnosis (HR 1.26, 95% confidence interval 1.07-1.47). CONCLUSIONS: In the first systematic investigation of the association between ADT and cataract, our results suggest an elevation in the incidence of cataract among ADT users. Further study, preferably prospective in design, is needed to provide additional evidence to support or refute these findings.

Interplay of race, socioeconomic status, and treatment on survival of patients with prostate cancer.

OBJECTIVES: To compare overall and prostate cancer-specific survival, using the Detroit Surveillance, Epidemiology, and End Results registry data, among 8679 Detroit area black and white men with localized or regional stage prostate cancer diagnosed from 1988 to 1992 to determine whether racial disparities in long-term survival remained after adjusting for treatment type and socioeconomic status (SES). METHODS: The cases were geocoded to the census block-group, and SES data were obtained from the 1990 U.S. Census. Cox proportional hazards regression analysis was used to estimate the hazard ratio of death from any cause. The median follow-up was 16.5 years. RESULTS: Of the 7770 localized stage cases (22% black and 78% white) and 909 regional cases (24% black and 76% white), black men were more likely to receive nonsurgical treatment (P < .001) and to be of low SES (P < .0001). The survival analyses were stratified by stage. For both stages, black men had poorer survival than white men in the unadjusted model. The adjustment for age and tumor grade had little effect on the survival differences, but adjustment for SES and treatment removed the survival differences. CONCLUSIONS: Low SES and nonsurgical treatment were associated with a greater risk of death among men with prostate cancer, explaining much of the survival disadvantage for black men with prostate cancer.

Patterns of cancer in first generation immigrants from the Arab League and other countries.

Arabic immigrants are a relatively new group of immigrants and one of the fastest growing populations in the United States. Yet, information about their disease patterns is limited because Arabic is not a recognized minority group in population statistics. We tested whether population-based cancer registry data were useful to describe cancer patterns of the first generation of Arabic immigrants, compared with non-immigrants as well as the first generation of other immigrants. Information on invasive cancer cases with only one primary and known age was extracted from Surveillance, Epidemiology, and End Results (SEER) public use data (1973-2004) and software. Immigrants were divided by place of birth; Arabic: born in the Arab League countries, and other immigrants: born in countries other than the United States or Arab League, whereas US-born were used as a reference population. Information on place of birth was frequently absent for non-deceased cases, therefore data were limited to deceased cases. Age- and gender-standardized proportional ratios (SPR) were calculated for 24 aggregated cancer sites. Significantly high or low SPRs were observed for Arabic immigrants for the following cancer sites: liver (3.15), gallbladder & other biliary (1.87), thyroid (1.74), stomach (1.54), leukemia (1.41), lymphoma (1.36), pancreas (1.36), ovary (1.29), brain and other nervous system (1.23), lung (0.80), prostate (0.72), oral cavity and pharynx (0.64), esophagus (0.39), and skin melanoma (0.33). These patterns were similar for the other immigrants; however, ovary and brain were Arabic-specific, and thus may deserve further investigation for specific environmental or genetic exposures among Arabic immigrants.

African American-preponderant single nucleotide polymorphisms (SNPs) and risk of breast cancer.

BACKGROUND: African American women more often present with more aggressive types of breast cancer than Caucasian women, but little is known whether genetic polymorphisms specific to or disproportionate in African Americans are associated with their risk of breast cancer. METHODS: A population-based case-control study was conducted including 194 cases identified through the Metropolitan Detroit Cancer Surveillance System and 189 controls recruited through random digit dialing to examine polymorphisms in genes involved in estrogen metabolism and action. RESULTS: The African American-specific CYP1A1 5639C allele was associated with an increased risk of breast cancer (odds ratio (OR)=2.34, 95% confidence interval (CI) 1.23-4.44) and this association with the CYP1A1 5639 locus was dependent on another polymorphism in the CYP3A4 gene (P=0.043 for the interaction). In addition, African American-predominant CYP1B1 432 Val allele was significantly more often found in the cases than in the controls overall and the HSD17B1 312 Gly allele was specifically associated with premenopausal breast cancer risk (OR=3.00, 95%CI 1.29-6.99). CONCLUSION: These observations need to be confirmed in larger studies due to the limited statistical power of the study based on a small number of cases.

Racial differences in colorectal cancer survival in the Detroit Metropolitan Area.

BACKGROUND: Colorectal carcinoma is the second most common cause of cancer death with African Americans having lower survival compared with White Americans. The purpose of this study was to investigate the effect of demographics, clinical factors, and socioeconomic status (SES) on racial disparities in colorectal cancer survival in the Detroit Metropolitan Area. METHODS: The study population included 9078 individuals with primary invasive colorectal cancer identified between 1988 and 1992 through the Surveillance, Epidemiology, and End Results (SEER) program. Demographics, clinical information, and survival were obtained through SEER. SES was categorized using occupation, educational level, and poverty status at the census tract level. Kaplan-Meier survival curves and Cox proportional hazards regression were used to compare overall survival by race. RESULTS: African Americans were more likely to be diagnosed with stage IV disease (P < .001), and to reside within poor census tracts (P < .001) compared with White Americans. Unadjusted analysis showed that African Americans had a significantly higher risk of death compared with their White American counterparts (hazards ratio [HR], 1.13; 95% confidence interval [CI], 1.07-1.20). After adjusting for age, marital status, sex, SES group, TNM stage, and treatment, race was no longer significantly associated with overall survival (HR, 1.00; 95% CI, 0.92-1.09). Similar results were seen with colorectal cancer-specific survival. CONCLUSIONS: Racial disparities in colorectal cancer survival dissipate after adjusting for other demographic and clinical factors. These results can potentially affect medical guidelines regarding screening and treatment, and possibly influence public health policies that can have a positive impact on equalizing racial differences in access to care.

The effectiveness of manual therapy in the management of musculoskeletal disorders of the shoulder: a systematic review.

A systematic review of randomised controlled trials (RCTs) was conducted to determine the effectiveness of manual therapy (MT) techniques for the management of musculoskeletal disorders of the shoulder. Seven electronic databases were searched up to January 2007, and reference lists of retrieved articles and relevant MT journals were screened. Fourteen RCTs met the inclusion criteria and their methodological qualities were assessed using the PEDro scale. Results were analyzed within diagnostic subgroups (adhesive capsulitis (AC), shoulder impingement syndrome [SIS], non-specific shoulder pain/dysfunction) and a qualitative analysis using levels of evidence to define treatment effectiveness was applied. For SIS, there was no clear evidence to suggest additional benefits of MT to other interventions. MT was not shown to be more effective than other conservative interventions for AC, however, massage and Mobilizations-with-Movement may be useful in comparison to no treatment for short-term outcomes for shoulder dysfunction.

Racial differences in cervical cancer survival in the Detroit metropolitan area.

BACKGROUND: African-American (AA) women have lower survival rates from cervical cancer compared with white women. The objective of this study was to examine the influence of socioeconomic status (SES) and other variables on racial disparities in overall survival among women with invasive cervical cancer. METHODS: One thousand thirty-six women (705 white women and 331 AA women) who were diagnosed with primary invasive cancer of the cervix between 1988 and 1992 were identified through the Metropolitan Detroit Cancer Surveillance System (MDCSS), a registry in the Surveillance, Epidemiology, and End Results (SEER) database. Pathology, treatment, and survival data were obtained through SEER. SES was categorized by using occupation, poverty, and educational status at the census tract level. Cox proportional hazards models were used to compare overall survival between AA women and white women adjusting for sociodemographics, clinical presentation, and treatment. RESULTS: AA women were more likely to present at an older age (P<.001), with later stage disease (P<.001), and with squamous histology (P=.01), and they were more likely to reside in a census tract categorized as Working Poor (WP) (P<.001). After multivariate adjustment, race no longer had a significant impact on survival. Women who resided in a WP census tract had a higher risk of death than women from a Professional census tract (P=.05). There was a significant interaction between disease stage and time with the effect of stage on survival attenuated after 6 years. CONCLUSIONS: In this study, factors that affected access to medical care appeared to have a more important influence than race on the long-term survival of women with invasive cervical cancer.

Disentangling the effects of race on breast cancer treatment.

BACKGROUND: African Americans (AA) have higher mortality from breast cancer compared with white Americans (WA). Studies using population-based cancer registries have attributed this to disparities in treatment after normalizing the AA and WA populations for differences in disease stage. However, those studies were hampered by lack of comorbidity data and limited information about systemic treatments. The objective of the current study was to investigate racial disparities in breast cancer treatment by conducting a comprehensive medical records review of women who were diagnosed with breast cancer at the Karmanos Cancer Institute (KCI) in Detroit, Michigan. METHODS: The study cohort consisted of 651 women who were diagnosed with primary breast cancer between 1990 and 1996 at KCI. Multivariable logistic regression analysis controlling for sociodemographic factors, tumor characteristics, comorbidities, and health insurance status was used to assess whether there were differences between WA and AA in the receipt of breast-conserving surgery (BCS), radiation, tamoxifen, and chemotherapy. RESULTS: There was no significant difference between WA and AA in the receipt of BCS versus mastectomy. Patients with local-stage disease who were enrolled in government insurance plans underwent mastectomy more often (vs BCS plus radiation) compared with patients who were enrolled in nongovernment plans. The rates of receipt of tamoxifen and chemotherapy were similar for local-stage WA and local-stage AA. However, WA were more likely to receive tamoxifen and/or chemotherapy for regional-stage disease. Married women with regional disease were more likely to receive chemotherapy than nonmarried women. CONCLUSIONS: The results from this study may be used to target educational interventions to improve the use of adjuvant therapies among AA women who have regional-stage disease.

Breast cancer risk estimates for relatives of white and African American women with breast cancer in the Women's Contraceptive and Reproductive Experiences Study.

PURPOSE: Family history is a well-recognized risk factor for breast cancer. Familial aggregation and segregation analyses have estimated breast cancer risk based on family history primarily for white women; such information is limited for African American (AA) women. The purpose of this report is to update breast cancer risk estimates associated with a family history of breast cancer for white and AA women. METHODS: We used family cancer history from 2,676 white and 1,525 AA women with breast cancer (probands) in the population-based National Institute of Child Health and Human Development's Women's Contraceptive and Reproductive Experiences (CARE) Study to estimate age-specific breast cancer risks in their first degree adult female relatives. Cumulative hazard curves were calculated for relatives of all probands using Cox proportional hazards models, and were stratified by the proband's race and age at diagnosis and number of relatives affected. RESULTS: Breast cancer risks for white and AA women with a family history of the disease are similar through age 49 years, but diverge afterwards, with higher risks by age 79 in white women than in AA women (17.5% [SE, 0.9%] v 12.2% [SE, 1.1%]; P < .001). These risks increase as the number of affected first degree relatives increases, reaching 25.2% (SE, 3.4%) and 16.9% (SE, 4.0%) in white and AA women with more than one affected relative, respectively (P = .3). CONCLUSION: We found age-related racial differences in breast cancer risk in women with a family history of breast cancer and have updated risk estimates for white and AA women for clinical use.

Racial differences in the familial aggregation of breast cancer and other female cancers.

Although breast cancer familial aggregation has been studied in Caucasians, information for African-Americans is scant. We used family cancer history from the Women's Contraceptive and Reproductive Experiences study to assess the aggregation of breast and gynecological cancers in African-American and Caucasian families. Information was available on 41,825 first and second-degree relatives of Caucasian and 28,956 relatives of African-American participants. We used a cohort approach in which the relative's cancer status was the outcome in unconditional logistic regression and adjusted for correlated data using generalized estimating equations. Race-specific models included a family history indicator, the relative's age, and type. Relative risk (RR) estimates for breast cancer were highest for first-degree relatives, and the overall RR for breast cancer among case relatives was 1.96 (95% CI = 1.68-2.30) for Caucasian and 1.78 (95% CI = 1.41-2.25) for African-Americans. The effect of CARE participants' reference age on their relatives' breast cancer risk was greatest among first-degree relatives of African-American patients with RRs (95% CI) for ages <45 and > or =45 of 2.97 (1.86-4.74) and 1.48 (1.14-1.92), respectively. Among Caucasians, first-degree relatives of case subjects were at greater risk for ovarian cancer, particularly relatives younger than 45 years (RR (95% CI) = 2.06 (1.02-4.12)), whereas African-American first-degree relatives of case subjects were at increased cervical cancer risk (RR (95% CI) = 2.17 (1.22-3.85). In conclusion, these racially distinct aggregation patterns may reflect different modes of inheritance and/or environmental factors that impact cancer risk.