RESUMEN
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.
RESUMEN
Background: An international collaborative study was conducted to determine the demographic and clinical profiles of Hispanic/Latinx endometriosis patients from Latin America and Spain using the Minimal Clinical Questionnaire developed by the World Endometriosis Research Foundation (WERF) Endometriosis Phenome and Biobanking Harmonization Project (EPHect). Methods: This is a cross-sectional study to collect self-reported data on demographics, lifestyle, and endometriosis symptoms of Hispanic/Latinx endometriosis patients from April 2019 to February 2020. The EPHect Minimal Clinical Questionnaire (EPQ-M) was translated into Spanish. Comprehension and length of the translated survey were assessed by Spanish-speaking women. An electronic link was distributed via social media of endometriosis patient associations from 11 Latin American countries and Spain. Descriptive statistics (frequency, means and SD, percentages, and proportions) and correlations were conducted using SPSSv26. Results: The questionnaire was completed by 1,378 participants from 23 countries; 94.6% had self-reported diagnosis of endometriosis. Diagnostic delay was 6.6 years. Most participants had higher education, private health insurance, and were employed. The most common symptoms were back/leg pain (85.4%) and fatigue (80.7%). The mean number of children was 1.5; 34.4% had miscarriages; the mean length of infertility was 3.7 years; 47.2% reported pregnancy complications. The most common hormone treatment was oral contraceptives (47.0%). The most common comorbidities were migraines (24.1%), polycystic ovary syndrome (PCOS) (22.2%), and irritable bowel syndrome (21.1%). Most participants (97.0%) experienced pelvic pain during menses; for 78.7%, pain was severe; 86.4% reported dyspareunia. The mean age of dysmenorrhea onset was 16.2 years (SD ± 6.1). Hormone treatments were underutilized, while impact was substantial. Pain catastrophizing scores were significantly correlated with pain intensity (p < 0.001). Conclusion: This is the first comprehensive effort to generate a clinical-demographic profile of Hispanic/Latinx endometriosis patients. Differences in clinical presentation compared to other cohorts included higher prevalence and severity of dysmenorrhea and dyspareunia and high levels of pain catastrophizing. Though future studies are needed to dissect the impact of race and ethnicity on pain and impact, this profile is the first step to facilitate the recognition of risk factors and diagnostic features and promote improved clinical management of this patient population. The EPHect questionnaire is an efficient tool to capture data to allow comparisons across ethnicities and geographic regions and tackle disparities in endometriosis research.