Carino Gurjao - Genetic Analyses of Colorectal Cancer across Ancestries and Mutagenic Exposures

ETHZ special presentation hosted by Valentina Boeva

  • 11:00 at ETHZ, Sonneggstrasse 3, 8092 Zürich

Abstract Colorectal cancer (CRC) has several established risk factors, including diet and microbiome. However, their mutagenic effect has not been observed directly in patients’ tumors and the individuals or ethnic groups who are most susceptible to diet-induced carcinogenesis are yet to be identified. In particular, CRC disproportionately affects African American (AA) patients who have worse clinical outcomes, but the molecular underpinnings are still poorly understood. We hypothesize that mutational signature analyses in CRC, coupled with epidemiologic, tumor molecular, micro-environmental, and patient germline data, can be linked to pre-diagnosis diet and specific germline alterations, which can further inform cancer prevention efforts.

We analyzed CRCs with whole-exome sequencing (WES) and performed integrated analyses of the cancer genome and microenvironment. We identified evidence of red meat-associated alkylating damage in CRCs. Tumor alkylating damage was enriched among individuals harboring the MGMT germline rs16906252 polymorphism. Genetic ancestry analyses further revealed distinct germline and microenvironmental features: in particular, rs16906252 was absent in East Asian and African CRC patients and synergistic with pre-diagnosis red meat intake. Together, these results have significant implications for dietary-induced carcinogenesis and precision prevention in CRC.

Bio Carino Gurjao’s research focuses on the omics analysis of cancer. He investigates DNA patterns in the tumor genome to better understand what factors shape these patterns and how they can, in return, inform clinical decisions. Carino previously wrote his dissertation under the supervision of Pr. Boeva (ETH) and Pr. Mirny (MIT) on the use of passenger mutations to treat and prevent cancer. Currently, he is a postdoctoral researcher at Columbia University, where he leads the analysis of the largest colorectal cancer sequencing cohort of African-American patients.