Abstract P2-09-06: Increased rates of genetic variants of unknown significance in Latino and African American populations of south Texas
Authors: Soewito Stephanie , Wyatt Rachel , Berenson Emily , Poullard Natalie , Gessay Shawn , Mette Lindsey , Shelby Kristin , Alvarez Elise , Aviles Clarissa , Saldivar Anna Maria Pulido , Otto Pamela , Jatoi Ismail , Kaklamani Virginia , Tomlinson Gail E 
Published: March 2022

Hereditary susceptibility studies for breast cancer are key to enhancing early detection and exercising prevention strategies in order to reduce breast cancer mortality. Germline pathogenic variants that have shown susceptibility to breast and ovarian cancer are detected in gene panels including ATM, BRCA1, BRCA2, BRIP1, CDH1, CDKN2A, CHEK2, DICER1, EPCAM, MLH1, MSH2, MSH6, NBN, NF1, PALB2, PMS2, PTEN, POLE, RAD50, RAD51C, RAD51D, RECQL, STK11, and TP53. Historically, minority populations have been overlooked both in reach and access to genetic testing, resulting in a lack of knowledge of the genomic landscape and creating a barrier to the application of genetics in clinical medicine. This is the case with the populations of South Texas including the Texas-Mexico border region. According to the US Census Bureau, the South Texas region population is comprised of 69% Hispanics while the Texas-Mexico border region population is comprised of over 90% Hispanics. Previous studies have shown multiple pathogenic variants and also variants of unknown significance (VUS) specific to ethnic populations and regions, but there is little information regarding the Mexican American population of South Texas.Our GRACIAS Texas Program has provided services to individuals and professionals across 26 counties in the South Texas area by specifically providing cancer genetic counseling and testing to individuals and families at highest risk. Recruitment was accomplished through comprehensive outreach to communities through health fairs, small group education sessions, mammography centers, hospitals, FQHCs, and direct interactions with medical providers. Although our program focused on recognizing both breast and colon cancer, and also reached those with rare cancer predisposition syndromes, the concern for breast cancer risk was most commonly addressed, accounting for the majority of cases. A total of 1595 individuals were identified as appropriate for cancer genetic counseling, and of these, 1377 individuals completed genetic testing. Of all individuals who received cancer genetic counseling, 1269 (79.5%) were Hispanic, 16% non-Hispanic White, 3% African American, and 1% other race/ethnicity. The group of individuals receiving testing consisted of 86% females and 14% males. Of those tested, 259 (18.8%) individuals were found to have pathogenic genetic variant and 187 (13.7%) individuals were found to have a VUS. Notedly, the VUS were nearly twice as common in the Hispanic population (14%) as compared to non-Hispanic White population (7.2%). This underscores the disparities of knowledge in genomic variation in Hispanic and non-Hispanic population. We also note that although the percentage of African American patients seen was small, 12 of 45 (26.6%) were found to have a VUS which further reflects the underrepresentation of African Americans in genomic landscape studies.These variants are important because they present a dilemma when advising patients as to need for cancer screening. However, recognition and further exploration of these VUS provide a future pathway to functional assessment and thus eventual knowledge to guide patient care. We continue to monitor for any changes to the status of these VUS. Although many variants are ultimately classified as benign variations, we have seen cases in which a VUS is reclassified into a likely pathogenic or definitely pathogenic variation having significant implications for screening, prevention, and management for these individuals and their families emphasizing further the need to continue to follow individuals tested. Our observations will help define the gene-specific risks of individuals and families in our underserved communities and will support the goal of closing gaps in genomic disparities.Supported by CPRIT grants PP120089 and PP160011 and NIH P30 CA54174.

Citation Format: Stephanie Soewito, Rachel Wyatt, Emily Berenson, Natalie Poullard, Shawn Gessay, Lindsey Mette, Kristin Shelby, Elise Alvarez, Clarissa Aviles, Anna Maria Pulido Saldivar, Pamela Otto, Ismail Jatoi, Virginia Kaklamani, Gail E Tomlinson. Increased rates of genetic variants of unknown significance in Latino and African American populations of south Texas [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-09-06.