Spectrum of somatic mutational features of colorectal tumors in ancestrally diverse populations.

Ancestrally diverse and admixed populations, including the Hispanic/Latino/a/x/e community, are underrepresented in cancer genetic and genomic studies. Leveraging the Latino Colorectal Cancer Consortium, we analyzed whole exome sequencing data on tumor/normal pairs from 718 individuals with colorectal cancer (128 Latino, 469 non-Latino) to map somatic mutational features by ethnicity and genetic ancestry. Global proportions of African, East Asian, European, and Native American ancestries were estimated using ADMIXTURE. Associations between global genetic ancestry and somatic mutational features across genes were examined using logistic regression. TP53 , APC , and KRAS were the most recurrently mutated genes. Compared to non-Latino individuals, tumors from Latino individuals had fewer KRAS (OR=0.64, 95%CI=0.41-0.97, p=0.037) and PIK3CA mutations (OR=0.55, 95%CI=0.31-0.98, p=0.043). Genetic ancestry was associated with presence of somatic mutations in 39 genes (FDR-adjusted LRT p<0.05). Among these genes, a 10% increase in African ancestry was associated with significantly higher odds of mutation in KNCN (OR=1.34, 95%CI=1.09-1.66, p=5.74×10 -3 ) and TMEM184B (OR=1.53, 95%CI=1.10-2.12, p=0.011). Among RMGs, we found evidence of association between genetic ancestry and mutation status in CDC27 (LRT p=0.0084) and between SMAD2 mutation status and AFR ancestry (OR=1.14, 95%CI=1.00-1.30, p=0.046). Ancestry was not associated with tumor mutational burden. Individuals with above-average Native American ancestry had a lower frequency of microsatellite instable (MSI-H) vs microsatellite stable tumors (OR=0.45, 95%CI=0.21-0.99, p=0.048). Our findings provide new knowledge about the relationship between ancestral haplotypes and somatic mutational profiles that may be useful in developing precision medicine approaches and provide additional insight into genomic contributions to cancer disparities. Significance: Our data in ancestrally diverse populations adds essential information to characterize mutational features in the colorectal cancer genome. These results will help enhance equity in the development of precision medicine strategies.

Survival Associated With Consolidated Multidisciplinary Care in Head and Neck Cancer: A Retrospective Cohort Study.

OBJECTIVE: To compare survival among patients with head and neck cancer before and after implementing a weekly multidisciplinary clinic and case conference. METHODS: A retrospective cohort study with chart review was conducted of 3081 patients (1431 preimplementation, 1650 postimplementation) diagnosed with stage I-IVB tumors in the oral cavity, oropharynx, hypopharynx, nasopharynx, or larynx. Pre- and postimplementation differences in overall and disease-specific survival 1, 2, and 3 years after diagnosis were assessed with unadjusted Kaplan-Meier curves and multivariable Cox proportional hazard regression models adjusted for demographic characteristics, comorbidity burden, smoking status, tumor site and stage, p16 status for oropharyngeal squamous cell cancer, and initial treatment modality. RESULTS: Patients less commonly presented with oropharyngeal squamous cell cancer and advanced tumors (III-IVB) and received primary treatment with surgery alone or with adjuvant therapy preimplementation than postimplementation. Overall survival at 3 years was 77.1% and 79.9% (P = .07) and disease-specific survival was 84.9% and 87.5% (P = .05) among pre- and postimplementation patients, respectively. At 3 years, preimplementation patients had slightly poorer overall (hazard ratio, 1.20; 95% CI, 1.02-1.40) and disease-specific (hazard ratio, 1.26; 95% CI, 1.03-1.54) adjusted survival than postimplementation patients. In unadjusted and adjusted analyses, survival improvements were more pronounced among patients with advanced disease. DISCUSSION: A multidisciplinary clinic and case conference were associated with improved outcomes among patients with head and neck cancer, especially those with advanced tumors. IMPLICATIONS FOR PRACTICE: All patients with head and neck cancer should receive multidisciplinary team management, especially those with advanced tumors.

DNA mismatch repair deficiency and hereditary syndromes in Latino patients with colorectal cancer.

BACKGROUND: The landscape of hereditary syndromes and clinicopathologic characteristics among US Latino/Hispanic individuals with colorectal cancer (CRC) remains poorly understood. METHODS: A total of 265 patients with CRC who were enrolled in the Hispanic Colorectal Cancer Study were included in the current study. Information regarding CRC risk factors was elicited through interviews, and treatment and survival data were abstracted from clinical charts. Tumor studies and germline genetic testing results were collected from medical records or performed using standard molecular methods. RESULTS: The mean age of the patients at the time of diagnosis was 53.7 years (standard deviation, 10.3 years), and 48.3% were female. Overall, 21.2% of patients reported a first-degree or second-degree relative with CRC; 3.4% met Amsterdam I/II criteria. With respect to Bethesda guidelines, 38.5% of patients met at least 1 criterion. Of the 161 individuals who had immunohistochemistry and/or microsatellite instability testing performed, 21 (13.0%) had mismatch repair (MMR)-deficient (dMMR) tumors. dMMR tumors were associated with female sex (61.9%), earlier age at the time of diagnosis (50.4 ± 12.4 years), proximal location (61.9%), and first-degree (23.8%) or second-degree (9.5%) family history of CRC. Among individuals with dMMR tumors, 13 (61.9%) had a germline MMR mutation (MutL homolog 1 [MLH1] in 6 patients; MutS homolog 2 [MSH2] in 4 patients; MutS homolog 6 [MHS6] in 2 patients; and PMS1 homolog 2, mismatch repair system component [PMS2] in 1 patient). The authors identified 2 additional MLH1 mutation carriers by genetic testing who had not received immunohistochemistry/microsatellite instability testing. In total, 5.7% of the entire cohort were confirmed to have Lynch syndrome. In addition, 6 individuals (2.3%) had a polyposis phenotype. CONCLUSIONS: The percentage of dMMR tumors noted among Latino individuals (13%) is similar to estimates in non-Hispanic white individuals. In the current study, the majority of individuals with dMMR tumors were confirmed to have Lynch syndrome. Cancer 2017. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. Cancer 2017;123:3732-3743. © 2017 American Cancer Society.

Complementary and Integrative Health Practices Among Hispanics Diagnosed with Colorectal Cancer: Utilization and Communication with Physicians.

OBJECTIVE: Complementary and integrative health (CIH) use among Hispanic adults with colorectal cancer (CRC) diagnosis is not well documented. Understanding the prevalence and patterns of CIH use among Hispanics offers insights to uncover potential needs for clinical services. DESIGN: Participants were age 21 years or older with a first-time diagnosis of CRC from population-based cancer registries in California. In-person and/or telephone-based interviews were administered to collect data on CIH use. Demographic and clinical diagnosis data were abstracted from medical records. Descriptive statistical and logistic regression was used to analyze the frequencies and associations between selected patient characteristics and CIH use. RESULTS: Among 631 Hispanic patients, 40.1% reported ever using CIH. Herbal products/dietary supplements were used most often (35.3%), followed by bodywork (16.5%), mind-body practices (7.8%), and homeopathy (6.7%). About 60% of participants reported CIH use to address specific health conditions; however, most patients did not discuss CIH use with their physicians (76.3%). Women reported higher CIH use than did men (45.1% versus 35.9%; odds ratio, 1.49 [95% confidence interval, 1.07-2.08]; p = 0.02). CIH use did not differ by clinical stage, time since diagnosis, or preferred language. CONCLUSIONS: CIH use is prevalent among Hispanic patients with CRC, especially women. Little communication about CIH use occurs between participants and their healthcare providers. Efforts aimed at improving integrative oncology services provide an opportunity to address such gaps in healthcare service.

Shared health characteristics in Hispanic colorectal cancer patients and their primary social support person following primary diagnosis.

PURPOSE: The aim of this paper was to determine individual and shared levels of psychosocial, behavioral, and symptomological health characteristics among Hispanics with recent history of cancer and their primary social support person (PSSP) in the years following diagnosis. PATIENTS AND METHODS: Recruited from a population-based cohort study were 409 Hispanic patients with a previous diagnosis of colorectal cancer. Forty-seven patients identified a PSSP, who assists with medical decision-making and health-related matters, who also participated in the study. Current behavioral (smoking, alcohol use, physical activity, and complementary and alternative medicine use), psychosocial (stress and mindfulness), and physical symptom (fatigue) data were obtained using validated instruments. Analyses tested the individual and shared (between patients and PSSPs) variance in these health measures. RESULTS: The sample was diagnosed on average 3.1 years (standard deviation = 1.7) prior to assessment. PSSPs were mainly spouses/partners (63%) or children (28%) of patients. Among patients, stress was positively associated with being a current smoker (p < 0.01) and with fatigue (r = 0.45, p < 0.001); stress was negatively correlated with mindfulness (r = -0.41, p < 0.001); mindfulness was negatively associated with smoking (odds ratio (OR) = 0.72, p < 0.01) and alcohol consumption (OR = 0.83, p < 0.05); the inverse relationship between mindfulness and fatigue was partially mediated through lower levels of stress (ß = -0.17, p < 0.001). Similar patterns were observed among PSSPs. Patient mindfulness was negatively correlated with PSSP stress (r = -0.45, p < 0.01). Complementary and alternative medicine use showed interdependence between patients and PSSPs for use of herbal remedies (OR = 6.2; p < 0.01) and bodywork (OR = 8.3, p < 0.05). CONCLUSION: Hispanic colorectal cancer patients and their PSSP share a common health milieu in the years following a cancer diagnosis, offering opportunities for advancing interpersonal intervention approaches in cancer care. Copyright © 2015 John Wiley & Sons, Ltd.