Abstract 790: Sex and race-dependent variations in the mutational landscape of clonal hematopoiesis

Abstract

Abstract Introduction: Clonal hematopoiesis of indeterminate potential (CHIP) has emerged as a significant precursor to hematological malignancies and is associated with several age-related diseases. Recent studies in relatively small disease specific cohorts have suggested that CHIP may exhibit variations among different races and between males and females raising intriguing questions about potential genetic and environmental influences. Understanding the differences in CHIP across races and between males and females may have implications for personalized cancer risk assessment and targeted therapeutic strategies. Methods: Patient’s data were obtained from the Cancer Therapy and Clonal hematopoiesis via cBioportal. The original study was designed to examine clonal hematopoiesis mutations that were found in blood samples obtained from 24,146 patients with non-hematological cancers and their tumor-blood pairs were analyzed using targeting sequencing data MSK-IMPACT (Memorial Sloan Kettering-IMPACT). The cohort consisted of 45.7% males and 54.3% females; including 6.8% Asians, 6.2% Blacks, and 76.3% Whites. We examined mutation frequencies among these racial groups and between genders, employing the two-sided Fisher's exact test and adjusting p-values for multiple comparisons. Differences were considered significant when both P value and Q values are less than 0.05. Results: DNMT3A mutations were substantially more prevalent in females than in males (38.94% vs 31.37%, p-value: <10−10, q-value: 6.19e−09), While ASXL1 mutations were more frequent in males than females (5.82% vs 2.69%, p-value: <10−10, q-value: 6.19e−09). In the racial cohorts with sufficient sample sizes, STAT5B and CSF1R mutations were most frequent in Asian (1.40% and 0.84%), followed by Black (0.98% and 0.24%) and White populations (0.29% and 0.09%), (p-value: 8.099e−04 and 7.490e−04, q-value: 0.0234 and 0.0232). Several other CHIP mutations were enriched in Black: RARA, SMAD2, CDKN1B, CENPA, CTLA4, EIF1AX, ELF3, MSI1, MYC, SOX17, AURKA. On the other hand, H3C1, H3C4, MYCL were enriched in the Asian cohort. Conclusion: Our analysis provides insights into the complex interplay of sex and racial factors in shaping CHIP mutation frequencies. As CHIP continues to gain recognition as a critical precursor to malignancies, understanding these variations contributes to refining our understanding of its underlying mechanisms and clinical implications. Citation Format: Kanaka Dhuri, Houda Alachkar. Sex and race-dependent variations in the mutational landscape of clonal hematopoiesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 790.