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Abstract Background: Colorectal cancer, one of the most lethal and prevalent cancers across the world, is in large part due to genetic mutations. The plasmacytoma variant translocation 1 (PVT1) gene has an established association with many cancers, including colorectal cancer. There is increasingly abundant data on the mechanisms of action of PVT1 leading to the initiation and progression of these cancers. Identifying PVT1 variants linked to cancer may lead to uncovering their utility as diagnostic or prognostic biomarkers. The All of Us Research hub contains a diverse set of data from hundreds of thousands of participants. Stratifying and comparing risk variants across racial and ethnic demographics may provide insight into disparities underlying disparate incidence of colorectal cancer amongst minoritized and medically underserved communities. The All of Us database provides a novel opportunity to study PVT1 variation in a large cohort of patients from racial backgrounds with demonstrated greater incidence, prevalence, and worse outcomes from colorectal cancer. Methods: We conducted a retrospective cohort study of patients in the All of Us Research hub. The cohort studied comprised 930 patients ranging in age from 18 to 70 years with colorectal cancer, and no additional cancer diagnosis noted. Racial and ethnic backgrounds were selected if there were at least 100 patients of identified background with colorectal cancer. These consisted of patients of: African American, non-Hispanic white, and Hispanic backgrounds. We extracted data from short-read whole genome sequencing. A filtered matrix was built comparing the genetic sequence of our cohort of cancer patients to the reference genome GRCh38. We then stratified the different variants by allelic frequency across the sample cohort to report the variants with the greatest frequencies. All analyses were conducted using Python on Jupyter Notebook in the All of Us Research platform. Results: The top 5 PVT1 variants with the greatest frequency in patients of the three chosen racial and ethnic backgrounds were identified and compared to find commonalities. Rs127920247 was a PVT1 risk variant shared by African American and Hispanic patients as the 2nd highest risk variant for both. The most frequent risk variants for each group is as follows: Rs128085054 for African Americans, Rs128139524 for Non-Hispanic White Americans, and Rs127870242 for Hispanic Americans. Conclusion: PVT1 risk variants in colorectal cancer can be uncovered from data in the All of Us Research hub. Thus, genetic risk variants for cancers can be uncovered from analysis of data available in the All of Us Research hub. Identification of specific PVT1 variants similarly prevalent in colorectal cancer amongst distinct racial and ethnic communities is a significant first step towards developing them as potential diagnostic or prognostic tools. Citation Format: Sujay Singh, Olorunseun Ogunwobi. PVT1 risk variant rs127920247 for colorectal cancer is shared by African American and Hispanic colorectal cancer patients abstract. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A011.
Singh et al. (Sat,) studied this question.