A comparative effectiveness education trial for lifestyle health behavior change in African Americans.

Obesity and excess weight are significant clinical and public health issues that disproportionately affect African Americans because of physical inactivity and unhealthy eating. We compared the effects of alternate behavioral interventions on obesity-related health behaviors. We conducted a comparative effectiveness education trial in a community-based sample of 530 adult African Americans. Outcomes variables were physical activity (PA) and fruit and vegetable intake. Outcomes were evaluated at baseline and 1-month following interventions about shared risk factors for cancer and cardiovascular disease (CVD) (integrated, INT) or CVD only (disease-specific). Significant increases were found in the proportion of participants who met PA guidelines from baseline (47.4%) to follow-up (52.4%) (P = 0.005). In the stratified analysis that were conducted to examine interaction between education and intervention group assignment, this effect was most apparent among participants who had ≤high school education and were randomized to INT (OR = 2.28, 95% CI = 1.04, 5.00, P = 0.04). Completing the intervention was associated with a 1.78 odds of meeting PA guidelines (95% CI = 1.02, 3.10, P = 0.04). Education about risk factors for chronic disease and evidence-based strategies for health behavior change may be useful for addressing obesity-related behaviors among African Americans.

Acceptance of a community-based navigator program for cancer control among urban African Americans.

Patient navigation is now a standard component of cancer care in many oncology facilities, but a fundamental question for navigator programs, especially in medically underserved populations, is whether or not individuals will use this service. In this study, we evaluated acceptance of a community-based navigator program for cancer control and identified factors having significant independent associations with navigation acceptance in an urban sample of African Americans. Participants were African American men and women ages 50-75 who were residents in an urban metropolitan city who were referred for navigation. Of 240 participants, 76% completed navigation. Age and perceived risk of developing cancer had a significant independent association with navigation acceptance. Participants who believed that they were at high risk for developing cancer had a lower likelihood of completing navigation compared with those who believed that they had a low risk for developing this disease. The likelihood of completing navigation increased with increases in age. None of the socioeconomic factors or health care variables had a significant association with navigation acceptance. There are few barriers to using community-based navigation for cancer control among urban African Americans. Continued efforts are needed to develop and implement community-based programs for cancer control that are easy to use and address the needs of medically underserved populations.

Collective efficacy and obesity-related health behaviors in a community sample of African Americans.

The social environment is important to body mass index and obesity. However, it is unknown if perceptions of the social environment are associated with obesity-related behaviors in populations at greatest risk for being overweight or obese. We evaluated the relationship between collective efficacy and diet and physical activity in a community-based sample of African American adults who were residents in an urban area. Data were collected as part of an academic-community partnership from November 2009 to 2011. We evaluated whether participants met the recommended guidelines for diet and physical activity based on collective efficacy and their sociodemographic background, health care variables, and self-efficacy in a community-based sample of African American adults (n = 338) who were residents in the Philadelphia, PA metropolitan area. Overall, many participants did not meet the recommended guidelines for fruit and vegetable intake or physical activity. The likelihood of meeting the recommended guidelines for fruit intake increased with greater levels of collective efficacy (OR 1.56, 95 % CI 1.18, 2.07, p = 0.002) and self-efficacy for diet (OR 1.56, 95 % CI 1.19, 2.04, p = 0.001). Collective efficacy was not associated with physical activity and the positive association between collective efficacy and vegetable intake was not statistically significant (OR 1.25, 95 % CI 0.94, 1.65, p = 0.12). It is important to determine the most effective methods and settings for improving diet and physical activity behaviors in urban African Americans. Enhancing collective efficacy may be important to improving adherence to recommended guidelines for obesity-related health behaviors.

Germline Exome Sequencing for Men with Testicular Germ Cell Tumor Reveals Coding Defects in Chromosomal Segregation and Protein-targeting Genes.

BACKGROUND: Testicular germ cell tumor (TGCT) is the most common cancer among young White men. TGCT is highly heritable, although there are no known high-penetrance predisposition genes. CHEK2 is associated with moderate TGCT risk. OBJECTIVE: To identify coding genomic variants associated with predisposition to TGCT. DESIGN, SETTING, AND PARTICIPANTS: The study involved 293 men with familial or bilateral (high risk; HR)-TGCT representing 228 unique families and 3157 cancer-free controls. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We carried out exome sequencing and gene burden analysis to identify associations with TGCT risk. RESULTS AND LIMITATIONS: Gene burden association identified several genes, including loss-of-function variants of NIN and QRSL1. We identified no statistically significant association with the sex- and germ-cell development pathways (hypergeometric overlap test: p = 0.65 for truncating variants, p = 0.47 for all variants) or evidence of associations with the regions previously identified via genome-wide association studies (GWAS). When considering all significant coding variants together with genes associated with TGCT on GWAS, there were associations with three major pathways: mitosis/cell cycle (Gene Ontology identity GO:1903047: observed/expected variant ratio [O/E] 6.17, false discovery rate [FDR] 1.53 × 10-11), co-translational protein targeting (GO:0006613: O/E 18.62, FDR 1.35 × 10-10), and sex differentiation (GO:0007548: O/E 5.25, FDR 1.90 × 10-4). CONCLUSIONS: To the best of our knowledge, this study is the largest to date on men with HR-TGCT. As in previous studies, we identified associations with variants for several genes, suggesting multigenic heritability. We identified associations with co-translational protein targeting, and chromosomal segregation and sex determination, identified via GWAS. Our results suggest potentially druggable targets for TGCT prevention or treatment. PATIENT SUMMARY: We searched for gene variations that increase the risk of testicular cancer and found numerous new specific variants that contribute to this risk. Our results support the idea that many gene variants inherited together contribute to the risk of testicular cancer.

Low rates of African American participation in genetic counseling and testing for BRCA1/2 mutations: racial disparities or just a difference?

Low rates of genetic counseling among African American women have generated concerns about disparities; however, to the extent that women's decisions to accept or decline counseling are consistent with their values, then lower participation may reflect preferences and not disparities. We evaluated the extent to which women were satisfied with their decision about participating in genetic counseling for BRCA1/2 mutations and identified variables that were associated significantly with satisfaction. Prospective study of decision satisfaction with 135 African American women who had a minimum 5% prior probability of having a BRCA1/2 mutation. Decision satisfaction was evaluated one month after women were offered participation in genetic counseling using a structured questionnaire. Women were satisfied with their participation decision; more than 80% reported that their decision was consistent with their family values. However, women who declined pre-test counseling had significantly lower satisfaction scores. Our findings highlight the importance ensuring that racial differences that are due to preferences and values are not misclassified as disparities in order to identify and address the root causes of disparate treatment.

Understanding participation by African Americans in cancer genetics research.

PURPOSE: Understanding genetic factors that contribute to racial differences in cancer outcomes may reduce racial disparities in cancer morbidity and mortality. Achieving this goal will be limited by low rates of African American participation in cancer genetics research. METHOD: We conducted a qualitative study with African American adults (n = 91) to understand attitudes about participating in cancer genetics research and to identify factors that are considered when making a decision about participating in this type of research. RESULTS: Participants would consider the potential benefits to themselves, family members, and their community when making a decision to participate in cancer genetics research. However, concerns about exploitation, distrust of researchers, and investigators' motives were also important to participation decisions. Individuals would also consider who has access to their personal information and what would happen to these data. Side effects, logistical issues, and the potential to gain knowledge about health issues were also described as important factors in decision making. CONCLUSION: African Americans may consider a number of ethical, legal, and social issues when making a decision to participate in cancer genetics research. These issues should be addressed as part of recruitment efforts.

Association Study between Polymorphisms in DNA Methylation-Related Genes and Testicular Germ Cell Tumor Risk.

BACKGROUND: Testicular germ cell tumors (TGCT), histologically classified as seminomas and nonseminomas, are believed to arise from primordial gonocytes, with the maturation process blocked when they are subjected to DNA methylation reprogramming. SNPs in DNA methylation machinery and folate-dependent one-carbon metabolism genes have been postulated to influence the proper establishment of DNA methylation. METHODS: In this pathway-focused investigation, we evaluated the association between 273 selected tag SNPs from 28 DNA methylation-related genes and TGCT risk. We carried out association analysis at individual SNP and gene-based level using summary statistics from the Genome Wide Association Study meta-analysis recently conducted by the international Testicular Cancer Consortium on 10,156 TGCT cases and 179,683 controls. RESULTS: In individual SNP analyses, seven SNPs, four mapping within MTHFR, were associated with TGCT risk after correction for multiple testing (q ≤ 0.05). Queries of public databases showed that three of these SNPs were associated with MTHFR changes in enzymatic activity (rs1801133) or expression level in testis tissue (rs12121543, rs1476413). Gene-based analyses revealed MTHFR (q = 8.4 × 10-4), methyl-CpG-binding protein 2 (MECP2; q = 2 × 10-3), and ZBTB4 (q = 0.03) as the top TGCT-associated genes. Stratifying by tumor histology, four MTHFR SNPs were associated with seminoma. In gene-based analysis MTHFR was associated with risk of seminoma (q = 2.8 × 10-4), but not with nonseminomatous tumors (q = 0.22). CONCLUSIONS: Genetic variants within MTHFR, potentially having an impact on the DNA methylation pattern, are associated with TGCT risk. IMPACT: This finding suggests that TGCT pathogenesis could be associated with the folate cycle status, and this relation could be partly due to hereditary factors.

Cultural, economic, and psychological predictors of colonoscopy in a national sample.

BACKGROUND: Although colorectal cancer (CRC) is the second leading cause of cancer death among adults in the US and colonoscopy is efficacious in reducing morbidity and mortality from CRC, screening rates are sub-optimal. Understanding the socioeconomic, cultural, and health care context within which decisions about colonoscopy are made allows physicians to address patients' most salient beliefs and values and other constraints when making screening recommendations. OBJECTIVE: To evaluate the direct and interactive effects of socioeconomics, health care variables, psychological characteristics, and cultural values on colonoscopy use. DESIGN, SETTING, PARTICIPANTS: National survey completed between January-August 2009 in a random sample of African American, white, and Hispanic adults ages 50-75 without cancer (n = 582). MAIN MEASURE: Self-reported colonoscopy use. KEY RESULTS: Only 59% of respondents reported having a colonoscopy. The likelihood of colonoscopy increased with having health insurance (OR = 2.82, 95% CI = 1.24, 6.43, p = 0.004), and increasing age (OR = 1.40, 95% CI = 1.11, 1.77, p = 0.001). In addition, respondents with greater self-efficacy were more likely to have a colonoscopy (OR = 2.41, 95% CI = 1.35, 4.29, p = 0.003). CONCLUSIONS: Programs that help patients to overcome access and psychological barriers to screening are needed.

Using a mixed-methods approach to identify health concerns in an African American community.

OBJECTIVES: We used qualitative and quantitative data collection methods to identify the health concerns of African American residents in an urban community and analyzed the extent to which there were consistencies across methods in the concerns identified. METHODS: We completed 9 focus groups with 51 residents, 27 key informant interviews, and 201 community health surveys with a random sample of community residents to identify the health issues participants considered of greatest importance. We then compared the issues identified through these methods. RESULTS: Focus group participants and key informants gave priority to cancer and cardiovascular diseases, but most respondents in the community health survey indicated that sexually transmitted diseases, substance abuse, and obesity were conditions in need of intervention. How respondents ranked their concerns varied in the qualitative versus the quantitative methods. CONCLUSIONS: Using qualitative and quantitative approaches simultaneously is useful in determining community health concerns. Although quantitative approaches yield concrete evidence of community needs, qualitative approaches provide a context for how these issues can be addressed. Researchers should develop creative ways to address multiple issues that arise when using a mixed-methods approach.

Identification of 22 susceptibility loci associated with testicular germ cell tumors.

Testicular germ cell tumors (TGCT) are the most common tumor in young white men and have a high heritability. In this study, the international Testicular Cancer Consortium assemble 10,156 and 179,683 men with and without TGCT, respectively, for a genome-wide association study. This meta-analysis identifies 22 TGCT susceptibility loci, bringing the total to 78, which account for 44% of disease heritability. Men with a polygenic risk score (PRS) in the 95th percentile have a 6.8-fold increased risk of TGCT compared to men with median scores. Among men with independent TGCT risk factors such as cryptorchidism, the PRS may guide screening decisions with the goal of reducing treatment-related complications causing long-term morbidity in survivors. These findings emphasize the interconnected nature of two known pathways that promote TGCT susceptibility: male germ cell development within its somatic niche and regulation of chromosomal division and structure, and implicate an additional biological pathway, mRNA translation.

Sociocultural determinants of men's reactions to prostate cancer diagnosis.

OBJECTIVE: To develop a better understanding of how men react to being diagnosed with prostate cancer and identify factors that influence these responses, we conducted an observational study to identify sociocultural predictors of men's psychological reactions. METHODS: Participants were 70 African American and 124 white prostate cancer patients who completed a structured telephone interview that evaluated psychological reactions in terms of intrusive thoughts about cancer and attempts to avoid cancer-related thoughts and feelings. Perceptions of disease-specific stress, cultural beliefs and values, and social constraints were also assessed during the interview. RESULTS: There were no racial differences in men's reactions to being diagnosed with prostate cancer; however, greater perceptions of disease-specific stress, increasing levels of present temporal orientation, and more social constraints had significant positive effects on avoidant reactions. Greater perceptions of stress also had a significant positive effect on intrusive thoughts. CONCLUSIONS: The results of this study highlight the need for individualized approaches to help men address their thoughts and feelings about being diagnosed with prostate cancer. These efforts should include strategies that help men to communicate more effectively with social support resources and address cultural beliefs and values related to temporal orientation.

Participation rates and representativeness of African Americans recruited to a health promotion program.

When using community-based participatory methods to develop health promotion programs for specific communities, it is important to determine if participation differs based on sociodemographics and the extent to which program participants are demographically representative of the target community, especially when non-random recruitment methods are used. We evaluated rates of participating in a health promotion program among African American residents in an urban community and determined if program participants were representative of community residents in terms of sociodemographic factors. While participation in the program was modest, participation did not differ based on psychological factors or body mass index. However, individuals who were unemployed were significantly more likely to participate in the program compared with those who were employed. Our sample included a greater proportion of individuals who only had a high school education compared with community residents but was similar to community residents in terms of gender, marital status and employment.

Effects of integrated risk counseling for cancer and cardiovascular disease in African Americans.

OBJECTIVE: We evaluated a risk counseling intervention designed to enhance understanding about risk factors for cancer and cardiovascular disease, to improve self-efficacy for diet and physical activity, and to increase intentions to eat healthier and be physically active. METHODS: We conducted a quasi-experimental study developed by academic investigators and community stakeholders to evaluate the effects of integrated risk counseling in a community-based sample of African American adults (n = 101). The intervention provided education about the overlap in risk factors for cancer and cardiovascular disease and included components from motivational interviewing. RESULTS: Changes in behavioral intentions were not statistically significant (p > .05). Participants reported significantly greater levels of self-efficacy for diet (t = 2.25, p = .03) and physical activity (t = 2.55, p = .01), and significantly increased perceived risks of developing colon cancer (chi2 = 3.86, p = .05) and having a heart attack (chi2 = 4.50, p = .03). CONCLUSIONS: Integrated risk counseling may have some benefits among African Americans.

Lower abdominal and pelvic radiation and testicular germ cell tumor risk.

BACKGROUND: Testicular germ cell tumor (TGCT) incidence has increased in recent decades along with the use and dose of diagnostic radiation. Here we examine the association between reported exposure to diagnostic radiation and TGCT risk. METHODS: We conducted a case-control study of men with and without TGCT recruited from hospital- and population-based settings. Participants reported on exposures to 1) x-ray or CT below the waist and 2) lower GI series or barium enema, which consists of a series of x-rays of the colon. We also derived a combined measure of exposure. We used logistic regression to determine the risk of developing TGCT according to categories of exposures (0, 1-2, or ≥3 exposures) and age at first exposure, adjusting for age, year of birth, race, county, body mass index at diagnosis, family history of TGCT, and personal history of cryptorchidism. RESULTS: There were 315 men with TGCT and 931 men without TGCT in our study. Compared to no exposures, risk of TGCT was significantly elevated among those reporting at least three exposures to x-ray or CT (OR≥3 exposures, 1.78; 95% CI, 1.15-2.76; p = 0.010), lower GI series or barium enema (OR≥3 exposures, 4.58; 95% CI, 2.39-8.76; p<0.001), and the combined exposure variable (OR≥3 exposures, 1.59; 95% CI, 1.05-2.42; p = 0.029). The risk of TGCT was elevated for those exposed to diagnostic radiation at age 0-10 years, compared to those first exposed at age 18 years or later, although this association did not reach statistical significance (OR, 2.00; 95% CI, 0.91-4.42; p = 0.086). CONCLUSIONS: Exposure to diagnostic radiation below the waist may increase TGCT risk. If these results are validated, efforts to reduce diagnostic radiation doses to the testes should be prioritized.

Mutation Rates in Cancer Susceptibility Genes in Patients With Breast Cancer With Multiple Primary Cancers.

PURPOSE: Women with breast cancer have a 4%-16% lifetime risk of a second primary cancer. Whether mutations in genes other than BRCA1/2 are enriched in patients with breast and another primary cancer over those with a single breast cancer (S-BC) is unknown. PATIENTS AND METHODS: We identified pathogenic germline mutations in 17 cancer susceptibility genes in patients with BRCA1/2-negative breast cancer in 2 different cohorts: cohort 1, high-risk breast cancer program (multiple primary breast cancer [MP-BC], n = 551; S-BC, n = 449) and cohort 2, familial breast cancer research study (MP-BC, n = 340; S-BC, n = 1,464). Mutation rates in these 2 cohorts were compared with a control data set (Exome Aggregation Consortium [ExAC]). RESULTS: Overall, pathogenic mutation rates for autosomal, dominantly inherited genes were higher in patients with MP-BC versus S-BC in both cohorts (8.5% v 4.9% [P = .02] and 7.1% v 4.2% [P = .03]). There were differences in individual gene mutation rates between cohorts. In both cohorts, younger age at first breast cancer was associated with higher mutation rates; the age of non-breast cancers was unrelated to mutation rate. TP53 and MSH6 mutations were significantly enriched in patients with MP-BC but not S-BC, whereas ATM and PALB2 mutations were significantly enriched in both groups compared with ExAC. CONCLUSION: Mutation rates are at least 7% in all patients with BRCA1/2 mutation-negative MP-BC, regardless of age at diagnosis of breast cancer, with mutation rates up to 25% in patients with a first breast cancer diagnosed at age < 30 years. Our results suggest that all patients with breast cancer with a second primary cancer, regardless of age of onset, should undergo multigene panel testing.

Utilization of religious coping strategies among African American women at increased risk for hereditary breast and ovarian cancer.

This observational study evaluated utilization of religious coping strategies among 95 African American women who were at increased risk for having a BRCA1/BRCA2 (BRCA1/2) mutation. Overall, women reported high levels of collaborative coping; however, women with fewer than 2 affected relatives (beta = -1.97, P = 0.04) and those who had a lower perceived risk of having a BRCA1/2 mutation (beta = -2.72, P = 0.01) reported significantly greater collaborative coping. These results suggest that African American women may be likely to use collaborative strategies to cope with cancer-related stressors. It may be important to discuss utilization of religious coping efforts during genetic counseling with African American women.

Retention of African American women in cancer genetics research.

Although retention is a critical component of longitudinal cancer genetics research, limited empirical data are available on predictors of study retention among populations that are difficult to enroll. We evaluated predictors of retention in cancer genetics research among African American women at increased risk for having a BRCA1 and BRCA2 (BRCA1/2) mutation. Participants were African American women (n = 192) at increased risk for hereditary breast-ovarian cancer who were enrolled in a longitudinal genetic counseling research study. Retention was evaluated separately for the 1- and 6-month follow-ups and in terms of overall retention (e.g., completion of both telephone interviews). Seventy-three percent of women and 65% of women were retained at the 1- and 6-month follow-ups respectively; in terms of overall retention, 60% of women were retained in both follow-up telephone interviews. Predictors of retention at 1-month included being employed (OR = 2.47, 95% CI = 1.24, 4.93, P = 0.01) whereas predictors of overall retention included having a personal history of breast and/or ovarian cancer (OR = 2.06, 95% CI = 1.07, 3.95, P = 0.03) and having completed genetic counseling (OR = 2.63, 95% CI = 1.39, 4.98, P = 0.003). These data suggest that once enrolled in genetic counseling research, the majority of African American women will continue to participate, especially if concrete clinical services are provided.

Experiences with weight change in African-American breast cancer survivors.

Although weight gain is a common side effect of breast cancer treatment, limited empirical data are available on how African-American breast cancer survivors react to changes in their weight following diagnosis and treatment. The purpose of this study was to explore psychological and behavioral reactions to weight change in African-American breast cancer survivors. We conducted a qualitative study to explore reactions to weight change following diagnosis and treatment in 34 African-American breast cancer survivors. Forty-seven percent of women reported gaining weight, 32% reported weight loss, and 21% reported no changes in their weight. Regardless of whether women gained or lost weight, these changes were viewed as stressors that caused psychological distress and health concerns. However, some women had positive reactions to weight loss, especially if they had been heavy prior to diagnosis. Women exercised and changed their dietary behaviors following treatment. Despite this, women reported being frustrated with not being able to control changes in their weight. These results suggest that changes in weight may be a critical component of breast cancer survivorship in African-American women. It may be important to provide African-American breast cancer survivors with information about the causes and implications of weight change and strategies for weight control after treatment as part of their follow-up care.

Sociocultural predictors of breast cancer risk perceptions in African American breast cancer survivors.

Although African American breast cancer survivors are at increased risk for developing breast cancer again, empirical data are not available on breast cancer risk perceptions in these women. This study characterized perceived risk of developing breast cancer in African American breast cancer survivors at risk for having a BRCA1 or BRCA1 (BRCA1/2) mutation and identified factors having significant independent associations with risk perceptions. Participants were 95 African American breast cancer survivors at an increased risk for having a BRCA1/2 mutation. Risk perceptions and sociodemographic, clinical, treatment, and sociocultural factors were collected during a structured telephone interview. Most women reported that they had the same or lower risk of developing breast cancer again compared with other women (53%); however, a substantial minority of women (47%) reported that they had a higher or much higher risk. Factors having significant independent associations with heightened risk perceptions included having a >or=10% prior probability of having a BRCA1/2 mutation [odds ratio (OR), 2.91; 95% confidence interval (95% CI), 1.09-7.72; P = 0.03] and more years of formal education (OR, 2.74; 95% CI, 1.02-7.36; P = 0.05). In addition, women who thought about the past a lot were three times more likely to report heightened risk perceptions compared with those who did not think about the past a lot (OR, 3.72; 95% CI, 1.45-9.57; P = 0.01). These results suggest that it may be important to ensure adequate risk comprehension among African American women as part of genetic counseling for inherited breast-ovarian cancer risk. Discussion of risk perceptions within the context of existing beliefs and values may facilitate this process.

Recruiting African American women to participate in hereditary breast cancer research.

PURPOSE: This study evaluated the process of recruiting African American women to participate in genetic counseling research for BRCA1 and BRCA2 (BRCA1/2) mutations with respect to referral, study enrollment, and participation in genetic counseling. PATIENTS AND METHODS: African American women (n = 783) were referred for study enrollment. RESULTS: Of 783 referrals, 164 (21%) women were eligible for enrollment. Eligible women were most likely to be referred from oncology clinics (44%) and were least likely to be referred from general medical practices (11%; chi(2) = 96.80; P = .0001). Overall, 62% of eligible women enrolled onto the study and 50% of enrollees completed genetic counseling. Women with a stronger family history of cancer (odds ratio [OR] = 3.18; 95% CI, 1.36 to 7.44; P = .01) and those referred from oncology clinics and community oncology resources (OR = 2.97; 95% CI, 1.34 to 6.58; P = .01) were most likely to enroll onto the study. Referral from oncology clinics was associated significantly with participation in genetic counseling (OR = 5.46; 95% CI, 1.44 to 20.60; P = .01). CONCLUSION: Despite receiving a large number of referrals, only a small subset of women were eligible for enrollment. Oncology settings were the most effective at identifying eligible African American women and general medical practices were the least effective. Factors associated with enrollment included having a stronger family history of cancer and being referred from oncology clinics and community oncology resources. Referral from oncology clinics was the only factor associated significantly with participation in genetic counseling. Education about hereditary breast cancer may be needed among primary care providers to enhance appropriate referral of African American women to genetic counseling for BRCA1/2 mutations.