Abstract To understand multiple myeloma (MM) incidence and survivorship disparities, we established the Precision MEDicine, EqUity and Disparities Research in MultipLe MyeLomA (MEDULLA) study. Our study contacted 400 MM patients reported to the Cancer Registry of Greater California (CRGC) between 2013-2018. We contacted 100 adult individuals from four racial/ethnic groups: Blacks, Whites, Latinos, and Asians with MM diagnosis. Data collection included variables reported to the CRGC, a self-administered survey, and biospecimen saliva collection. The survey focused on demographics, risk factors, cancer treatment, family history, quality of life, and social determinants of health. We also used census tract level features obtained by the American Community Survey 2007-2011. A total of 95 patients participated in the survey (overall response rate = 24%). We performed chi-square test, fisher’s exact test, or Wilcoxon test to obtain two-sided p-values for univariate testing for associations with responding to the survey. We further perform multivariable logistic regression using a stepwise approach under the Akaike information criterion with age and sex kept as covariates. These methods were stratified by Whites and Non-Whites separately which we were able to find important trends. The highest response received was from Whites at 44.2%, with significantly lower rates in all minority groups (<20% for all groups). Response rates were higher for patients living in areas with higher median annual incomes and education. For every 1% increase in poverty rates, Whites living in such neighborhoods were 3% less likely to respond to the survey (p=0.04). For every 10% increase in the proportion of individuals having a college degree, responding to the survey increased by 1.17 units for minorities in that neighborhood (p=0.07). Minorities living in neighborhoods with high proportions of adults without a high school diploma and high unemployment rates are less likely to respond (p=0.02 and p=0.047, respectively). In conclusion, we found significantly lower participation rates among minority groups, with socio-economic factors affecting response rates. We suggest that future studies develop community-focused and culturally tailored strategies to understand MM etiology and survivorship in such populations. Citation Format: April P. Vang, Angelica Perez, Juanita Elizabeth Quino, Ana Estrada, Eric Stewart, Rosemary Cress, Luis Carvajal-Carmona. A multi-ethnic population-based study of multiple myeloma disparities: Results from a recruitment pilot [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B113.
<p>Figure S1 shows the Clustering of 1,990 non-admixed reference samples and 2,387 admixed samples(brown) individuals based on the first three principal components. Colors represent the continental ances</p>
Abstract Background and Aim: Familial juvenile polyposis syndrome (JPS) is a rare autosomal dominant condition in which patients develop hamartomatous gastrointestinal polyps with malignant potential. Pathogenic germline mutations in both the SMAD4 and BMPR1A genes involved in the transforming growth factor β pathway account for 40% of cases of JPS. Genetic heterogeneity remains evident, as the balance of cases is not accounted for by mutations in these genes. The aim of this study was to determine the mutation responsible in a family with juvenile polyposis. Methods: An Australian Caucasian family with juvenile polyposis have attended and followed surveillance plans through the Familial Bowel Cancer Clinic, The Royal Melbourne Hospital. A pedigree of the family was constructed with attention to the mixed phenotypic expression of polyps in affected members. Genetic testing for SMAD4 and BMPR1A mutations in germline DNA and linkage analysis to SMAD4 , BMPR1A and 15q14 ( CRAC1 locus) were performed. Results: There were no pathogenic mutations in SMAD4 and BMPR1A . There was no linkage to SMAD4 or 15q14 ( CRAC1 locus). Linkage analysis suggested a cryptic BMPR1A mutation or the presence of another gene in close proximity to the BMPR1A locus. Two additional candidate genes in the region of linkage ( PTEN and MINPP1 ) were excluded. Conclusion: Most affected members of this Australian Caucasian family demonstrate a phenotype of mixed polyps: juvenile polyps, adenomas and/or hyperplastic polyps. Cloning of a potentially responsible gene closely linked to the BMPR1A locus or a cryptic mutation in BMPR1A may offer valuable insights into the pathogenesis of JPS.
Abstract Cancer is a leading cause of non-communicable morbidity and mortality worldwide. While many genes that predispose individuals for different cancers have been discovered, the population prevalence of mutations in these genes remains largely undetermined in many populations. Developing customized screening panels and screening for novel variants for a large population samples can be expensive and time consuming. We have developed a low-cost high-throughput pipeline and method to screen 480 customizable amplicons (∼20 genes, ∼144Kbp) for up to 384 samples per run. By combining a bioinformatics pipeline for design and analysis with Fluidigm microfluidics PCR and Illumina MiSeq, we can quickly screen the full coding sequence of multiple cancer panels at a high depth of coverage at a low cost per sample (∼$20-40/sample). The amplicon design pipeline provides ability to develop amplicon primer sets and pooling strategies. Libraries of 384 barcoded samples are run in a single MiSeq lane. Sequencing data is analyzed by an automated pipeline, which aligns using BWA-MEM, calls variants using VarScan 2, and annotates variants using multiple datasets using Annovar. We have applied these pipelines and methods to identify mutation in known cancer genes, such as APC, MSH2, MLH1, BRCA1, and BRCA2, in several hundred Hispanic individuals with familial and early-onset colon and breast cancer. While many of these mutations have been previously reported, we have identified several novel pathogenic changes that appear to have Amerindian origin. Of which, a few are shared among many individuals in isolated geographic locations, suggesting founder effects are common in some of these populations. In conclusion, we have developed a low-cost high-throughput method for screening customizable panels for known and novel mutations. These panels typically consist of 20 cancer genes and our group has already developed panels that are specific for breast cancer, colon cancer and thyroid cancer. Our study is an initial step to assess prevalence of known cancer causing genes and identify novel genes/mutations that contribute to different cancers in the Hispanic community. These discoveries provide a foundation for early detection, prevention, and treatment of familial cancers. Citation Format: Ruta Sahasrabudhe,, Paul Lott, Anna Marie Tuazon, John Williamson, Natalia Belter, Ana Estrada, Mabel Bohorquez, Rodrigo Prieto, Angel Criollo, Alejandro Velez, Jorge Castro, Gilbert Mateus, Magdalena Echhevery, Luis G. Carvajal-Carmona. Development of low-cost high-throughput screening methods for detecting germline mutations in multiple cancer genes. [abstract]. In: Proceedings of the AACR Special Conference: Cancer Susceptibility and Cancer Susceptibility Syndromes; Jan 29-Feb 1, 2014; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(23 Suppl):Abstract nr 42. doi:10.1158/1538-7445.CANSUSC14-42
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