Race/Ethnicity and Accuracy of Self-Reported Female First-Degree Family History of Breast and Other Cancers in the Northern California Breast Cancer Family Registry.

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.

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.

Association of Breast Cancer Knowledge With Receipt of Guideline-Recommended Breast Cancer Treatment.

PURPOSE: Knowledge about one's breast cancer characteristics is poor, but whether this knowledge affects treatment is uncertain. Among women with breast cancer, we examined whether tumor knowledge was associated with adjuvant treatment receipt. METHODS: We surveyed a population-based sample of women in Northern California with stage 0 to III breast cancer diagnosed during 2010 to 2011 (participation rate, 68.5%). Interviews were conducted between 4 months and 3 years after diagnosis. Among 414 respondents with stage I to III disease, we examined receipt of guideline-recommended chemotherapy, radiation, and hormonal therapy by reporting correct information about one's tumor, including stage, estrogen receptor, human epidermal growth factor receptor 2 (HER2), and grade (using registry data for confirmation). We performed multivariate logistic regression to assess the probability of receiving each treatment in relevant patient groups, adjusting for patient and tumor characteristics, and examined the impact of reporting correct tumor information on treatment receipt. RESULTS: Among relevant treatment-eligible groups, 81% received chemotherapy, 91% received radiation, and 83% received hormonal therapy. In adjusted analyses, having correct (v incorrect) information for stage and HER2 were associated with chemotherapy receipt (odds ratio [OR], 4.45; 95% CI, 1.50 to 12.50 for stage; OR, 2.70; 95% CI, 1.02 to 7.18 for HER2). Correctly reporting estrogen receptor status was associated with hormonal therapy receipt (OR, 3.91; 95% CI, 1.73 to 8.86), and correctly reporting stage was associated with radiation receipt (OR, 2.76; 95% CI, 1.03 to 7.40). CONCLUSION: Knowledge about one's tumor characteristics was strongly associated with receipt of recommended therapies. Interventions to improve patients' knowledge and understanding of their cancers should be tested as a strategy for improving receipt of care.

Survival among Never-Smokers with Lung Cancer in the Cancer Care Outcomes Research and Surveillance Study.

RATIONALE: Differences in patient characteristics and outcomes have been observed among current, former, and never-smokers with lung cancer, but most prior studies included few never-smokers and were not prospective. OBJECTIVES: We used data from a large, prospective study of lung cancer care and outcomes in the United States to compare characteristics of never-smokers and smokers with lung cancer and to examine survival among the never-smokers. METHODS: Smoking status at diagnosis was determined by self-report and survival was determined from medical records and cancer registries, with follow-up through June 2010 or later. Cox regression was used to examine the association between smoking and survival, and to identify predictors of survival among never-smokers. MEASUREMENTS AND MAIN RESULTS: Among 3,410 patients with lung cancer diagnosed between September 1, 2003 and October 14, 2005 who completed a baseline patient survey, there were 274 never-smokers (8%), 1,612 former smokers (47%), 1,496 current smokers or smokers who quit recently (44%), and 28 with missing information about smoking status (<1%). Never-smokers appeared more likely than former and current/recent smokers to be female and of Asian or Hispanic race/ethnicity, and to have adenocarcinoma histology, fewer comorbidities, private insurance, and higher income and education. Compared with never-smokers, the adjusted hazard of death from any cause was 29% higher among former smokers (hazard ratio, 1.29; 95% confidence interval, 1.08-1.55), and 39% higher among current/recent smokers (hazard ratio, 1.39; 95% confidence interval, 1.16-1.67). Factors predicting worse overall survival among never-smokers included Hispanic ethnicity, severe comorbidity, undifferentiated histology, and regional or distant stage. Never-smoking Hispanics appeared more likely to have regional or advanced disease at diagnosis and less likely to undergo surgical resection, although these differences were not statistically significant. CONCLUSIONS: Never-smokers with lung cancer are more likely than ever-smokers to be female, Asian or Hispanic, and more advantaged socioeconomically, suggesting possible etiologic differences in lung cancer by smoking status. Among never-smokers, Hispanics with lung cancer had worse survival than non-Hispanic whites.

Population-Based Testing and Treatment Characteristics for Chronic Myelogenous Leukemia.

INTRODUCTION: National and international hematology/oncology practice guidelines recommend testing for the BCR-ABL mutation for definitive diagnosis of chronic myeloid leukemia (CML) to allow for appropriate treatment with a tyrosine kinase inhibitor (TKI). The purpose of our study was to describe population-based testing and treatment practice characteristics for patients diagnosed with CML. METHODS: We analyzed cases of CML using 2011 data from 10 state registries that are part of the Centers for Disease Control and Prevention (CDC)'s National Program of Cancer Registries. We describe completeness of testing for the BCR-ABL gene and availability of outpatient treatment with TKIs and associated characteristics. RESULTS: A total of 685 cases of CML were identified; 55 percent (374) had a documented BCR-ABL gene test with 96 percent (360) of these being positive for the BCR-ABL gene and the remaining 4 percent (14) either testing negative or having a missing result. Registries were able to identify the use of TKIs in 54 percent (369) of patients, though only 43 percent (296) had a corresponding BCR-ABL gene test documented. One state registry reported a significantly lower percentage of patients being tested for the BCR-ABL gene (25 percent) and receiving TKI treatment (21 percent). Limiting analysis to CML case reports from the remaining 9 comparative effectiveness research registries, 78 percent (305) patients had a documented BCR-ABL gene test and 79 percent (308) had documented treatment with a TKI. Receipt of testing or treatment for these 9 states did not vary by sex, race, ethnicity, census tract poverty level, census tract urbanization, or insurance status; BCR-ABL testing varied by state of residence, and BCR-ABL testing and TKI therapy occurred less often with increasing age (BCR-ABL testing: odds ratio [OR], 0.97; 95 percent CI, 0.95-0.99; and TKI therapy: OR, 0.97; 95 percent CI, 0.96-0.99). CONCLUSIONS: Collection of detailed CML data vary significantly by states. A majority of the case patients had appropriate testing for the BCR-ABL gene and treatment with tyrosine kinase inhibitors. However, BCR-ABL testing and TKI treatment decreased with increasing age. Further research is needed to understand CML coding, testing, and treatment disparities.

Higher Stage of Disease Is Associated With Bilateral Mastectomy Among Patients With Breast Cancer: A Population-Based Survey.

BACKGROUND: The reasons for increasing rates of bilateral mastectomy for unilateral breast cancer are incompletely understood, and associations of disease stage with bilateral surgery have been inconsistent. We examined associations of clinical and sociodemographic factors, including stage, with surgery type and reconstruction receipt among women with breast cancer. PATIENTS AND METHODS: We surveyed a diverse population-based sample of women from Northern California cancer registries with stage 0 to III breast cancer diagnosed during 2010-2011 (participation rate, 68.5%). Using multinomial logistic regression, we examined factors associated with bilateral and unilateral mastectomy (vs. breast-conserving surgery), adjusting for tumor and sociodemographic characteristics. In a second model, we examined factors associated with reconstruction for mastectomy-treated patients. RESULTS: Among 487 participants, 58% had breast-conserving surgery, 32% had unilateral mastectomy, and 10% underwent bilateral mastectomy. In adjusted analyses, women with stage III (vs. stage 0) cancers had higher odds of bilateral mastectomy (odds ratio [OR], 8.28; 95% confidence interval, 2.32-29.50); women with stage II and III (vs. stage 0) disease had higher odds of unilateral mastectomy. Higher (vs. lower) income was also associated with bilateral mastectomy, while age ≥ 60 years (vs. < 50 years) was associated with lower odds of bilateral surgery. Among mastectomy-treated patients (n = 206), bilateral mastectomy, unmarried status, and higher education and income were all associated with reconstruction (P < .05). CONCLUSION: In this population-based cohort, women with the greatest risk of distant recurrence were most likely to undergo bilateral mastectomy despite a lack of clear medical benefit, raising concern for overtreatment. Our findings highlight the need for interventions to assure women are making informed surgical decisions.

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.

KRAS testing and first-line treatment among patients diagnosed with metastatic colorectal cancer using population data from ten National Program of Cancer Registries in the United States.

BACKGROUND: In 2011, the National Comprehensive Cancer Network (NCCN) recommended KRAS testing for metastatic colorectal cancer (mCRC) patients. Our study assessed KRAS testing prevalence and its association with socio-demographic and clinical factors and examined first-line treatment. METHODS: Ten state population-based registries supported by Centers for Disease Control and Prevention's (CDC) National Program of Cancer Registries (NPCR) collected detailed cancer information on mCRC cases diagnosed in 2011, including KRAS biomarker testing and first-line treatment from ten central cancer registries. Data were analyzed with Chi-square tests and multivariate logistic regression. RESULTS: Of the 3,608 mCRC cases, 27% (n = 992) had a documented KRAS test. Increased age at diagnosis (p < 0.0001), racial/ethnic minorities (p = 0.0155), public insurance (p = 0.0018), and lower census tract education (p = 0.0023) were associated with less KRAS testing. Significant geographic variation in KRAS testing (p < 0.0001) ranged from 46% in New Hampshire to 18% in California. After adjusting for all covariates, age and residence at diagnosis (both p < 0.0001) remained predictors of KRAS testing. Non-Hispanic Blacks had less KRAS testing than non-Hispanic Whites (OR = 0.77, 95% CI = 0.61-0.97). Among those tested and found to have normal (wild-type) KRAS, 7% received anti-EGFR treatment; none received such treatment among those with KRAS mutated gene. CONCLUSIONS: Despite NCCN guideline recommendations, 73% of mCRC cases diagnosed in 2011 had no documented KRAS test. Disparities in KRAS testing existed based on age, race, and residence at diagnosis. IMPACT: These findings show the capacity of monitoring KRAS testing in the US using cancer registry data and suggest the need to understand the low uptake of KRAS testing, and associated treatment choices during the first year since diagnosis.

Racial/Ethnic Differences in Patients' Selection of Surgeons and Hospitals for Breast Cancer Surgery.

IMPORTANCE: Racial differences in breast cancer treatment may result in part from differences in the surgeons and hospitals from whom patients receive their care. However, little is known about differences in patients' selection of surgeons and hospitals. OBJECTIVE: To examine racial/ethnic differences in how women selected their surgeons and hospitals for breast cancer surgery. DESIGN, SETTING, AND PARTICIPANTS: We surveyed 500 women (222 non-Hispanic white, 142 non-Hispanic black, 89 English-speaking Hispanic, and 47 Spanish-speaking Hispanic) from northern California cancer registries with stage 0 to III breast cancer diagnosed during 2010 through 2011. We used multivariable logistic regression to assess the reasons for surgeon and hospital selection by race/ethnicity, adjusting for other patient characteristics. We also assessed the association between reasons for physician selection and patients' ratings of their surgeon and hospital. MAIN OUTCOMES AND MEASURES: Reasons for surgeon and hospital selection and ratings of surgeon and hospital. RESULTS: The 500 participants represented a response rate of 47.8% and a participation rate of 69%. The most frequently reported reason for surgeon selection was referral by another physician (78%); the most frequently reported reason for hospital selection was because it was a part of a patient's health plan (58%). After adjustment, 79% to 87% of black and Spanish-speaking Hispanic women reported selecting their surgeon based on a physician's referral vs 76% of white women (P = .007). Black and Hispanic patients were less likely than white patients to report selecting their surgeon based on reputation (adjusted rates, 18% and 22% of black and Hispanic women, respectively, vs 32% of white women; P = .02). Black and Hispanic women were also less likely than white women to select their hospital based on reputation (adjusted rates, 7% and 15% vs 23%, respectively; P = .003). Women who selected their surgeon based on reputation more often rated the care from their surgeon as excellent (adjusted odds ratio, 2.21; 95% CI, 1.24-3.93); those reporting their surgeon was one of the only surgeons available through the health plan less often reported excellent quality of surgical care (adjusted odds ratio, 0.56; 95% CI, 0.34-0.91). CONCLUSIONS AND RELEVANCE: Compared with white patients with breast cancer, minority patients were less actively involved in physician and hospital selection, relying more on physician referral and health plans rather than on reputation. Interventions to promote involvement in surgeon and hospital selection may have potential for addressing disparities related to lower-quality care from surgeons and hospitals.

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.

Enhancing cancer registry data for comparative effectiveness research (CER) project: overview and methodology.

Following the Institute of Medicine's 2009 report on the national priorities for comparative effectiveness research (CER), funding for support of CER became available in 2009 through the American Recovery and Re-investment Act. The Centers for Disease Control and Prevention (CDC) received funding to enhance the infrastructure of population-based cancer registries and to expand registry data collection to support CER. The CDC established 10 specialized registries within the National Program of Cancer Registries (NPCR) to enhance data collection for all cancers and to address targeted CER questions, including the clinical use and prognostic value of specific biomarkers. The project also included a special focus on detailed first course of treatment for cancers of the breast, colon, and rectum, as well as chronic myeloid leukemia (CML) diagnosed in 2011. This paper describes the methodology and the work conducted by the CDC and the NPCR specialized registries in collecting data for the 4 special focused cancers, including the selection of additional data variables, development of data collection tools and software modifications, institutional review board approvals, training, collection of detailed first course of treatment, and quality assurance. It also presents the characteristics of the study population and discusses the strengths and limitations of using population-based cancer registries to support CER as well as the potential future role of population-based cancer registries in assessing the quality of patient care and cancer control.

Trans-ethnic genome-wide association study of colorectal cancer identifies a new susceptibility locus in VTI1A.

The genetic basis of sporadic colorectal cancer (CRC) is not well explained by known risk polymorphisms. Here we perform a meta-analysis of two genome-wide association studies in 2,627 cases and 3,797 controls of Japanese ancestry and 1,894 cases and 4,703 controls of African ancestry, to identify genetic variants that contribute to CRC susceptibility. We replicate genome-wide statistically significant associations (P<5 × 10(-8)) in 16,823 cases and 18,211 controls of European ancestry. This study reveals a new pan-ethnic CRC risk locus at 10q25 (rs12241008, intronic to VTI1A; P=1.4 × 10(-9)), providing additional insight into the aetiology of CRC and highlighting the value of association mapping in diverse populations.

Treatment and Mortality in Men with Localized Prostate Cancer: A Population-Based Study in California.

PURPOSE: To provide patients and physicians with population-based estimates of mortality from prostate cancer or other causes depending upon the primary treatment modality, stratified by patient age, tumor stage and grade. METHODS: We conducted a 10-year competing-risk analysis of 45,440 men diagnosed with clinically localized (T1 or T2) prostate cancer in California during 1995-1998. Information on patient characteristics, primary treatment and cause of death was obtained from the California Cancer Registry. RESULTS: In this population-based cohort, the most common primary treatment was surgery (40.4%), followed by radiotherapy (29.1%), conservative management (20.8%), and androgen deprivation therapy (ADT) monotherapy (9.8%). Prostate cancer mortality differed significantly (p < 0.0001) across treatment groups among patients <80 years at diagnosis with moderately or poorly differentiated disease; the 10-year disease-specific mortality rates were generally highest for men treated with ADT monotherapy [range: 3.3% (95% CI=0.8-12.5%) to 53.8% (95% CI=34.4-72.2%)], intermediate for men treated with conservative management [range: 1.7% (95% CI=0.7-4.6%) to 30.0% (95% CI=16.2-48.8%] or radiotherapy [range: 3.2% (95% CI=1.8-5.5%) to 18.3% (95% CI=15.1-22.0%)], and lowest for men treated with surgery [range: 1.2% (95% CI=0.8-1.7%) to 11.0% (95% CI=8.4-14.2%)]. CONCLUSION: The cause-specific mortality estimates provided by this observational study can help patients and physicians better understand the expected long-term outcomes of localized prostate cancer given the initial treatment choice and practice patterns in the general population.

Enrollment of patients with lung and colorectal cancers onto clinical trials.

PURPOSE: Only 2% to 5% of adult patients with cancer enroll onto clinical trials. We assessed simultaneously characteristics of patients and their physicians that may be independently associated with participation. METHODS: CanCORS, a National Cancer Institute (NCI) -funded population-based observational cohort study of newly diagnosed patients with lung and colorectal cancers, sampled patients across five geographic areas, five health care delivery systems, and 15 Veterans Administration hospitals. We linked patient survey and medical record data with physician survey data to examine correlates of trial enrollment. RESULTS: Among 9,901 patients, 5.3% enrolled onto trials. Of the 9,901 patients, we linked 6,506 patients to one medical oncologist, surgeon, or radiation oncologist (physicians, N = 1,325) who responded to the physician survey and was considered their primary cancer clinician decision maker. Patient age, race, disease stage, geographic region, and health insurance were independently associated with trial enrollment. Physician factors independently associated with patient trial enrollment were being a medical oncologist, practicing at an NCI-designated cancer center, taking the lead in discussing trials with patients, and receiving increased income from trial enrollment. After simultaneously adjusting for patient and physician characteristics, only being a physician practicing at an NCI-designated cancer center (odds ratio [OR], 1.65; 95% CI, 1.19 to 2.27) and patient female sex (OR, 1.36; 95% CI, 1.10 to 1.68), age > 70 versus < 50 years (OR, 0.28; 95% CI, 0.16 to 0.48), and advanced disease (OR, 1.85; 95% CI, 1.45 to 2.37) remained independently associated with trial enrollment. CONCLUSION: Both practice environment and patient clinical and demographic characteristics are associated with cancer clinical trial enrollment; simultaneous intervention may be required when trying to increase enrollment rates.

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.

Diagnostic chest X-rays and breast cancer risk before age 50 years for BRCA1 and BRCA2 mutation carriers.

BACKGROUND: The effects of low-dose medical radiation on breast cancer risk are uncertain, and few studies have included genetically susceptible women, such as those who carry germline BRCA1 and BRCA2 mutations. METHODS: We studied 454 BRCA1 and 273 BRCA2 mutation carriers ages younger than 50 years from three breast cancer family registries in the United States, Canada, and Australia/New Zealand. We estimated breast cancer risk associated with diagnostic chest X-rays by comparing mutation carriers with breast cancer (cases) with those without breast cancer (controls). Exposure to chest X-rays was self-reported. Mammograms were not considered in the analysis. RESULTS: After adjusting for known risk factors for breast cancer, the ORs for a history of diagnostic chest X-rays, excluding those for tuberculosis or pneumonia, were 1.16 [95% confidence interval (CI), 0.64-2.11] for BRCA1 mutations carriers and 1.22 (95% CI, 0.62-2.42) for BRCA2 mutations carriers. The OR was statistically elevated for BRCA2 mutation carriers with three to five diagnostic chest X-rays (P = 0.01) but not for those with six or more chest X-rays. Few women reported chest fluoroscopy for tuberculosis or chest X-rays for pneumonia; the OR estimates were elevated, but not statistically significant, for BRCA1 mutation carriers. CONCLUSIONS: Our findings do not support a positive association between diagnostic chest X-rays and breast cancer risk before the ages of 50 years for BRCA1 or BRCA2 mutation carriers. IMPACT: Given the increasing use of diagnostic imaging involving higher ionizing radiation doses, further studies of genetically predisposed women are warranted.

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.

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.