Profiling the Somatic Mutational Landscape of Breast Tumors from Hispanic/Latina Women Reveals Conserved and Unique Characteristics.

Somatic mutational profiling is increasingly being used to identify potential targets for breast cancer. However, limited tumor-sequencing data from Hispanic/Latinas (H/L) are available to guide treatment. To address this gap, we performed whole-exome sequencing (WES) and RNA sequencing on 146 tumors and WES of matched germline DNA from 140 H/L women in California. Tumor intrinsic subtype, somatic mutations, copy-number alterations, and expression profiles of the tumors were characterized and compared with data from tumors of non-Hispanic White (White) women in The Cancer Genome Atlas (TCGA). Eight genes were significantly mutated in the H/L tumors including PIK3CA, TP53, GATA3, MAP3K1, CDH1, CBFB, PTEN, and RUNX1; the prevalence of mutations in these genes was similar to that observed in White women in TCGA. Four previously reported Catalogue of Somatic Mutations in Cancer (COSMIC) mutation signatures (1, 2, 3, 13) were found in the H/L dataset, along with signature 16 that has not been previously reported in other breast cancer datasets. Recurrent amplifications were observed in breast cancer drivers including MYC, FGFR1, CCND1, and ERBB2, as well as a recurrent amplification in 17q11.2 associated with high KIAA0100 gene expression that has been implicated in breast cancer aggressiveness. In conclusion, this study identified a higher prevalence of COSMIC signature 16 and a recurrent copy-number amplification affecting expression of KIAA0100 in breast tumors from H/L compared with White women. These results highlight the necessity of studying underrepresented populations. SIGNIFICANCE: Comprehensive characterization of genomic and transcriptomic alterations in breast tumors from Hispanic/Latina patients reveals distinct genetic alterations and signatures, demonstrating the importance of inclusive studies to ensure equitable care for patients. See related commentary by Schmit et al., p. 2443.

HPV Vaccine recommendations: does a health care provider's gender and ethnicity matter to Unvaccinated Latina college women?

Objectives: There are disparities in the uptake of HPV vaccine among racial/ethnic minority women. The strongest predictor of HPV vaccine uptake among adult women is health care provider (HCP) recommendation; however, it is unclear how issues relating to race/ethnicity may mitigate these recommendations. Research shows that racial/ethnic and gender concordance between a patient and HCP can improve patient satisfaction, access and quality of care. If concordance contributes to improved patient-provider interactions, then it may be a factor in patient decisions regarding HPV vaccination. The objectives of this study were to (1) explore gender and ethnicity HCP preference regarding HPV vaccination among unvaccinated; and (2) understand factors associated with those preferences. Design: Unvaccinated Latina college students (n = 187) completed a survey that assessed HCP preferences, medical mistrust, cultural assimilation and HPV vaccine recommendation. Logistic regression models evaluated associations between above variables with HPV knowledge and preference for a female and/or Latina HCP. Results: Most respondents had health insurance (71%), a regular HCP (64%), were US-born (67%), with foreign-born parents (74%). Thirty-four percent and 18% agreed that they would be more likely to get the HPV vaccine if the recommending HCP was female and Latino, respectively. Latina women reporting higher medical mistrust preferred a HPV vaccine recommendation from a Latino/a provider. Conclusions: Latinas' preferences regarding gender and ethnicity of their HCPs may affect patient-provider interactions. Increasing diversity and cultural awareness among HCPs, and providing linguistically and culturally-appropriate information may decrease patient-provider mistrust, increase uptake of the HPV vaccine, and decrease persistent cervical cancer disparities.

Examining HPV Awareness, Sexual Behavior, and Intent to Receive the HPV Vaccine Among Racial/Ethnic Male College Students 18-27 years.

Human papillomavirus (HPV) awareness and vaccination among males in the general population is low. Men in general, but particularly racial/ethnic men, are disproportionately affected by HPV. The purpose of this article is to examine college males' (a) HPV awareness, (b) sexual behaviors, and (c) intention to receive the HPV vaccination. A non-probability sample of all students who self-reported their race/ethnicity and were attending a university in Southeastern United States were contacted by the university registrar's office and recruited to participate in the 15-minute survey. Males, ages 18-27 years ( N = 190), were identified for this study. χ2, t-tests, and binomial logistic regression analyses assessed the relationship between knowing about HPV and HPV vaccine and the intent to receive the HPV vaccination. Findings indicated that 67.4% of the sample identified as Hispanic or Black. Among all men, 73.2% reported previous sexual experience and 49.5% were currently sexually active. There were 79.5% who had previous knowledge about HPV and 55.8% had knowledge about the HPV vaccine; 71.1% of the sample did not intend to receive the vaccine. Hispanic and Black men were less likely to identify as virgins, more likely to be sexually active, and more likely to have sexual experiences at an earlier age compared to White, Asian, and other men. Men with previous HPV vaccine knowledge (28.4%) were more likely to intend to receive the vaccine compared to men who did not have previous knowledge about the vaccine (14.9%). Providing males with information about HPV, its transmission, and possible HPV-related outcomes may increase HPV vaccine uptake.

Depression severity is associated with increased inflammation in veterans with peripheral artery disease.

The present study examines the association between depressive symptoms and inflammatory markers in peripheral artery disease (PAD) to better understand the mechanistic relationship between depression and PAD. A cross-sectional sample of 117 patients with PAD (97% male, 76% Caucasian) was recruited from the San Francisco Veterans Affairs Medical Center. Patients were categorized into three subgroups based upon current depressive symptom severity, as defined by Patient Health Questionnaire-8 scores: no symptoms (score of 0-4, n = 62), mild symptoms (score of 5-9, n = 33), and moderate/severe symptoms (score ≥ 10, n = 22). Serum levels of high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), soluble intercellular adhesion molecule-1 (ICAM-1), and tumor necrosis factor-alpha (TNF-α) were assayed and log-transformed for multivariable analysis. To decrease the possibility of Type 1 errors, inflammatory markers were standardized and summed to create a total inflammatory score. In a multivariable analysis controlling for demographics, PAD severity, and atherosclerotic risk factors, mild and moderate/severe depressive symptoms were predictive of a higher total inflammatory score when compared to the group with no symptoms (mild symptoms p = 0.04, moderate/severe symptoms p = 0.007). Exploratory multivariable analyses of individual inflammatory markers found IL-6 levels were significantly higher in the moderate/severe symptoms group ( p = 0.006) than in the no symptoms group. Moreover, hs-CRP and ICAM-1 trended upwards with increasing depression severity. TNF-α was not associated with depression severity. We conclude that depressive symptom severity was independently associated with greater inflammation in PAD. Future research should examine the strength and directionality of this association through larger prospective cohort studies, as well as investigate the pathophysiological mechanisms responsible.

Assessing the Oral Health Needs of African American Men in Low-Income, Urban Communities.

Despite improvements in oral health status in the United States, pronounced racial/ethnic disparities exist. Black men are less likely to visit the dentist, are twice as likely to experience tooth decay, and have a significantly lower 5-year oral cancer survival rate when compared to White men. The Minority Men's Oral Health Dental Access Program employed a community-based participatory research approach to examine the oral health barriers and opportunities for intervention among Black men in a low-income, urban neighborhood. A cross-sectional study design was implemented through a self-administered survey completed among 154 Black males. The majority reported not having dental insurance (68.8%). Most frequently cited oral health care barriers were lack of dental insurance and not being able to afford dental care. Attitudes related to the significance of dental care centered on cancer prevention and feeling comfortable with one's smile. The impact of oral health on daily life centered on social interaction, with men citing insecurities associated with eating, talking, and smiling due to embarrassment with how their teeth/mouth looked to others. Multivariate logistic regression revealed that those who had difficulty finding dental care were 4.81 times (odds ratio = 4.65, 95% confidence interval [1.80, 12.85]) more likely to report no dental insurance, and 2.73 times (odds ratio = 3.72; 95% confidence interval [1.12, 6.70]) more likely to report poor oral health. Community-based participatory approaches include assessment of neighborhood residents affected by the health issue to frame interventions that resonate and are more effective. Social, physical, and infrastructural factors may emerge, requiring a multilevel approach.

HPV vaccine awareness and the association of trust in cancer information from physicians among males.

INTRODUCTION: Black and Hispanic men are diagnosed with more HPV-related cancers and at later stages compared to other racial/ethnic groups. Physician communication with men about HPV vaccination may be beneficial to increasing HPV vaccinations and decreasing HPV transmission. The purpose of this study was to examine HPV and HPV vaccine awareness among men by race, and the association between trust in cancer information from physicians and ever hearing about HPV and the HPV vaccine. METHODS: U.S. adult males (age 18+) were identified from the 2014 Health Information National Trends Survey (HINTS) (n=1203). Binomial logistic regression models assessed the influences of race/ethnicity and trust of cancer information from physicians on men having heard of HPV and the HPV vaccination. RESULTS: Approximately 50% of the sample had never heard of HPV and 53% had never heard of the vaccine. Black men were less likely to know that HPV is sexually transmitted compared to White and Hispanic men (p<0.001). Hispanic and Black men were less likely to have heard about the HPV vaccine when compared to White men (p<0.001). Additionally, Hispanic men were less likely to trust a doctor about cancer information compared to White and Black men (p<0.001). CONCLUSION: Findings highlight the lack of awareness about HPV among men. Furthermore, statistically significant racial/ethnic differences were found in HPV vaccine knowledge and trust in receiving cancer information from physicians. Future interventions should include community-based approaches and improved physicians' HPV-related communication to increase knowledge and uptake of the HPV vaccine.

Human Papillomavirus Vaccine Knowledge and Attitudes, Preventative Health Behaviors, and Medical Mistrust Among a Racially and Ethnically Diverse Sample of College Women.

INTRODUCTION: Medical mistrust is associated with disparities in a variety of health outcomes. The human papillomavirus (HPV) vaccine has the potential to decrease disparities in cervical cancer by preventing infection with the virus that causes these malignancies. No study has examined associations between medical mistrust and preventative health behaviors including the HPV vaccine among young minority women. METHODS: Self-reported racial/ethnic minority students completed a web-based survey in fall of 2011. Wilcoxon and Kruskal-Wallis were used to test differences in medical mistrust scores by demographics and health behaviors. RESULTS: Medical mistrust varied significantly by race with Black women reporting the highest scores. Women with no regular health-care provider (HCP) or who had difficulty talking to their provider had higher mistrust. Higher medical mistrust was associated with a preference to receive HPV vaccine recommendation from a HCP of the same race or ethnicity among unvaccinated women. Black and Asian women who had not received the HPV vaccine had higher mistrust scores than vaccinated women. Perceived difficulty in talking to a HCP was associated with ever having a Pap smear. DISCUSSION: Awareness of medical mistrust and the influence on health behaviors may aid in increasing delivery of quality health services for racial and ethnic minority populations. Further research among different populations is needed to elucidate impacts of medical mistrust and provider communication on preventative health behaviors.

Human papillomavirus vaccine intentions among males: a test of the Parallel Processing Model.

We investigated the cognitive and emotional reactions resulting from a human papillomavirus-related illness threat (i.e. testing positive for human papillomavirus) and the potential behavioral implications resulting from these psychosocial processes among men (N = 536). Structural equation modeling was used to explore a theoretical model explaining human papillomavirus vaccine intentions. The model fit the data well and explained 16 percent of the variance in vaccine intentions. Negative emotional response mediated the path between illness threat and vaccine intentions. Threat of genital warts was a salient concern and was positively associated with negative emotional response and subsequent vaccine intentions. Implications for vaccine promotion are discussed.

Confusion about Pap smears: lack of knowledge among high-risk women.

BACKGROUND: The impact of the Papanicolaou (Pap) smear on the prevention of cervical cancer is one of the greatest public health success stories. However, it is not clear if women understand the purpose of the Pap smear despite recent advancements and national attention over cervical cancer prevention. The purpose of this study was to examine Pap smear knowledge among three high-risk populations at different points in time. METHODS: Women from three separate human papillomavirus (HPV) psychosocial studies completed surveys assessing Pap smear knowledge: (1) HPV-positive women (prevaccine population in 2005-2006, n=154, mean age 23.5), (2) college women (postvaccine population in 2008, n=276, mean age 18.9), and (3) minority college women (postvaccine population in 2011, n=711, mean age 23.3). Frequencies and logistic regression were employed to examine associations between demographic factors and accurate knowledge of Pap smear testing within each study. RESULTS: Approximately one quarter of participants across all three samples did not know that the Pap smear is a test for cervical cancer. Participants also incorrectly believed that the Pap smear tests for HPV (82%-91%), vaginal infections (76%-92%), yeast infections (65%-86%), gonorrhea (55%-81%), herpes (53%-80%), HIV/AIDS (22%-59%), and pregnancy (17%-38%). Among all three studies, older age was the only factor significant with higher Pap knowledge. Higher HPV knowledge scores were significantly associated with higher Pap knowledge in studies 2 and 3 only. CONCLUSIONS: Knowledge about the purpose of the Pap smear remains low. Findings underscore the significant need for clear and consistent messages among high-risk women regarding the prevention of cervical cancer and other reproductive health conditions.

Ethnic and racial differences in HPV knowledge and vaccine intentions among men receiving HPV test results.

We examined factors associated with HPV vaccine intentions by racial/ethnic group among men participating in a HPV natural history study. HPV knowledge, vaccine intentions and perceived barriers were assessed among non-Hispanic White, non-Hispanic Black and Hispanic men. Men were tested for HPV every 6 months. After receiving test results from their previous visit, participants (N=477) reported their intentions for HPV vaccination in a computer-assisted survey instrument (CASI). Vaccine intentions were high among all respondents, although differences were found between racial and ethnic groups in awareness and knowledge of HPV and, vaccine intentions and perceived access and barriers to receiving the HPV vaccine. In order to effectively disseminate the vaccine among men, factors that may promote or inhibit vaccine acceptability need to be identified. Identifying these factors related to vaccine intentions among minority and majority men offers an opportunity for addressing barriers to health equity and, in turn, reductions in HPV-related disparities.

Influences on human papillomavirus vaccination status among female college students.

OBJECTIVE: In 2006, the Food and Drug Administration (FDA) approved the human papillomavirus (HPV) vaccine Gardasil® (Merck) for girls and women aged 9-26 years. Although the vaccine is ideally administered to 11 and 12 year olds, college-aged women may be uniquely at risk for HPV due to high rates of sexual activity and, thus, serve as an important catch-up population for the HPV vaccine. The purpose of this study is to examine factors associated with HPV vaccination status among college women. METHODS: In fall 2008, a convenience sample of 256 undergraduate women enrolled in an introductory social science course at a large, public, urban university in the southeastern United States was surveyed. The 30-item paper-and-pencil questionnaire asked for demographic information, HPV knowledge, HPV vaccine beliefs, and HPV vaccination status. The overall survey response rate was 89.6%. RESULTS: Most women were unmarried/single (91.7%), with a mean age of 18.9 years (range 17-42). Race/ethnicity status included 73.0% white, 17.5% Hispanic, and 7.7% black/African American. One hundred eleven (40.5%) women reported receiving the vaccine. Nonvaccinated women were less likely to have heard of the vaccine through a healthcare provider (odds ratio [OR] 0.12, 95% confidence interval [CI] 0.04-0.35) or from a family member (OR 0.33, 95% CI 0.16-0.68) and more likely to consider a healthcare provider recommendation as being only somewhat important (OR 2.91, 95% CI 1.32-6.41) or not important at all (OR 5.61, 95% CI 0.44-71.87) vs. very important. CONCLUSIONS: Findings suggest that healthcare providers have an important role in encouraging HPV vaccination. Continuing education for providers who see preadolescent girls in conjunction with a parent or who treat women of college age may be a worthwhile endeavor.

Human papillomavirus vaccine intentions among men participating in a human papillomavirus natural history study versus a comparison sample.

BACKGROUND: Human papillomavirus (HPV), the most common sexually transmitted virus in the United States, remains a considerable public health problem. HPV has been associated with anogenital warts and cancers in males and females, affecting the cervix, penis, anus, vulvar, and vaginal regions; and more recently, has been associated with oropharyngeal cancers. In 2006, the Food and Drug Administration (FDA) approved a prophylactic quadrivalent HPV vaccine for females (9-26 years); in 2009, this approval extended to males of this same age group. However, limited research has examined attitudes and other factors related to males' intention to receive the vaccine. METHODS: Factors associated with HPV vaccination intentions/willingness were examined among: (1) males (N=296) participating in a HPV natural history study with repeated exposure to HPV information; and (2) male University students (N=198) "unexposed" to intense HPV messages and testing. RESULTS: About 94% of HPV study participants and 62% of University males reported intentions/willingness toward vaccination, respectively. In multivariate analyses, among HPV study males, concerns about getting an appointment (odds ratio [OR], 0.06; confidence interval [CI], 0.01- 0.68), getting time off (OR, 0.14; CI, 0.03- 0.63), and "other" barriers (OR, 0.04; CI, 0.01- 0.17) were negatively associated with vaccine intentions. Among University males, vaccine awareness (OR, 0.06; CI, 0.02- 0.17), low risk perceptions (OR, 0.11; CI, 0.04-0.33), and unimportance of provider recommendations (OR, 9.66; CI, 2.69 -34.68) were negatively associated with willingness to vaccinate. CONCLUSION: Repeated exposure to HPV information and provider recommendations may be critical for male vaccine promotion. Future research is needed to increase understanding of factors that may prevent men from receiving HPV vaccination.

Integrated genetic and epigenetic analysis identifies three different subclasses of colon cancer.

Colon cancer has been viewed as the result of progressive accumulation of genetic and epigenetic abnormalities. However, this view does not fully reflect the molecular heterogeneity of the disease. We have analyzed both genetic (mutations of BRAF, KRAS, and p53 and microsatellite instability) and epigenetic alterations (DNA methylation of 27 CpG island promoter regions) in 97 primary colorectal cancer patients. Two clustering analyses on the basis of either epigenetic profiling or a combination of genetic and epigenetic profiling were performed to identify subclasses with distinct molecular signatures. Unsupervised hierarchical clustering of the DNA methylation data identified three distinct groups of colon cancers named CpG island methylator phenotype (CIMP) 1, CIMP2, and CIMP negative. Genetically, these three groups correspond to very distinct profiles. CIMP1 are characterized by MSI (80%) and BRAF mutations (53%) and rare KRAS and p53 mutations (16% and 11%, respectively). CIMP2 is associated with 92% KRAS mutations and rare MSI, BRAF, or p53 mutations (0, 4, and 31% respectively). CIMP-negative cases have a high rate of p53 mutations (71%) and lower rates of MSI (12%) or mutations of BRAF (2%) or KRAS (33%). Clustering based on both genetic and epigenetic parameters also identifies three distinct (and homogeneous) groups that largely overlap with the previous classification. The three groups are independent of age, gender, or stage, but CIMP1 and 2 are more common in proximal tumors. Together, our integrated genetic and epigenetic analysis reveals that colon cancers correspond to three molecularly distinct subclasses of disease.

Of mice and men: tyrosinase modification of congenital glaucoma in mice but not in humans.

PURPOSE: Primary congenital glaucoma (PCG) is an autosomal recessive ocular trait caused by mutations in the gene for cytochrome P4501B1 (CYP1B1). Although PCG is often considered to be fully penetrant, the disease shows 50% penetrance in some Saudi Arabian families. The familial segregation of the nonpenetrance suggests a genetic modifier. Recently, tyrosinase (Tyr) deficiency was found to worsen the drainage structure/ocular dysgenesis phenotype of Cyp1b1-/- mice, suggesting that Tyr is a modifier of the phenotype. In the current study, tyrosinase (TYR) was investigated in human PCG. METHODS: A genome-wide screen, a single nucleotide polymorphism (SNP) analysis in the TYR chromosomal region 11q13-q21, and sequencing of the TYR gene was performed with individuals from Saudi Arabian families with multiple, clinically confirmed, molecularly proven, nonpenetrant members. RESULTS: The study outcome did not support TYR as a modifier of the PCG phenotype in this population. The sequencing data showed no TYR mutations in the nonpenetrant family members and no difference in polymorphism frequencies between nonpenetrant or fully penetrant families. CONCLUSIONS: TYR is not a modifier of the CYP1B1-associated PCG phenotype in the Saudi Arabian population.

MGMT promoter methylation and field defect in sporadic colorectal cancer.

BACKGROUND: Sporadic colorectal cancers often arise from a region of cells characterized by a "field defect" that has not been well defined molecularly. DNA methylation has been proposed as a candidate mediator of this field defect. The DNA repair gene O6-methylguanine-DNA methyltransferase (MGMT) is frequently methylated in colorectal cancer. We hypothesized that MGMT methylation could be one of the mediators of field cancerization in the colon mucosa. METHODS: We studied MGMT promoter methylation by three different bisulfite-based techniques in tumor, adjacent mucosa, and non-adjacent mucosa from 95 colorectal cancer patients and in colon mucosa from 33 subjects with no evidence of cancer. Statistical tests were two-sided. RESULTS: MGMT promoter methylation was present in 46% of the tumors. Patients whose cancer had MGMT promoter methylation also had substantial MGMT promoter methylation in apparently normal adjacent mucosa. This methylation was seen with a quantitative assay in 50% (22/44; 95% confidence interval [CI] = 34% to 65%) of normal samples with MGMT promoter methylation in the adjacent tumors, 6% (3/51; 95% CI = 1% to 16%) of samples without MGMT methylation in adjacent tumors, and 12% (4/33; 95% CI = 3% to 28%) of control samples (P < .001 for comparison between each of the latter two groups and the first group). MGMT methylation was detected with a more sensitive assay in 94%, 34%, and 27% of these samples, respectively (P < .001). In grossly normal colonic mucosa of colon cancer patients, methylation was detected 10 cm away from the tumor in 10 of 13 cases. Tumors with MGMT promoter methylation had a higher rate of G-to-A mutation in the KRAS oncogene than tumors without MGMT promoter methylation (10/42 versus 3/46, P = .03). Using a sensitive mutant allele-specific amplification assay for KRAS mutations, we also found KRAS mutations in 12% (3/25; 95% CI = 2.5% to 31%) of colorectal mucosas with detectable MGMT methylation and 3% (2/64; 95% CI = 0.4% to 11%) of colorectal mucosas without MGMT methylation (P = .13). CONCLUSION: Some colorectal cancers arise from a field defect defined by epigenetic inactivation of MGMT. Detection of this abnormality may ultimately be useful in risk assessment for colorectal cancer.