Abstract LB-327: Colorectal cancer in Nigeria: High tech and low-tech approaches to improving patient outcomes

Abstract

Abstract Introduction: Cancer has become a major public health crisis in low- and middle-income countries. Colorectal cancer (CRC) rates, specifically, are rapidly rising in sub-Saharan Africa. The cause for this troubling trend is unknown. Compared with patients in the USA, stage-for-stage outcomes are significantly worse in West African patients, with an overall one-year survival rate of only 47%. Driven by the rapid rise in cancer rates, we founded the African Research Group for Oncology (ARGO) in 2013. ARGO is focused on developing strategies for cancer prevention and early detection, understanding tumor characteristics and answering clinical questions using prospective clinical databases and biobanks. The goal is to improve treatment options and outcomes for West African patients with cancer. We present the initial results of the genetic and epigenetic analysis of tumour specimens of patients recruited into the ARGO data base. and its prognostic implications. Methodology: All cases of CRC seen in all 5 ARGO affiliated institutions located in South west of Nigeria were recruited into the study using the RedCap data base for data collation. Each patient was staged using imaging (CT scan) and operative findings. Paired CRC samples were subjected to Integrated Mutation Profiling of Actionable Cancer Targets (IMPACT) Assay to study 300 cancer specific genes. The IMPACT Assay identified somatic variants that test for associations with patterns of metastases in Nigeria and the US. We also compared mismatch repair genes in the colon cancer primary tumors using immunohistochemistry. DNA from peripheral blood was used as a reference to determine the pattern of sporadic mutations. The reduced representation bisulfite sequencing (RRBS) method was used for methylation profiling. Results: Our biobank and clinical database includes biospecimens and data from over 400 prospectively enrolled CRC patients. It showed compelling differences in the pattern of disease in these patients, with higher rates of peritoneal metastases (61% Nigeria vs. 10% USA, p<0.01) and microsatellite instability (MSI-H: 28% Nigeria vs. 9.6% USA, p<0.01). Patients also present at a much younger age in West Africa, with a median age of 52 years (vs. 67 years in the USA). In addition to higher rates of MSI-H, 33% of Nigerian MSI-H patients had left sided tumors (vs. 15% in the USA). Only 22% of Nigerian patients who have MSI-H tumors have BRAF mutations (vs. more than 40% of MSI-H patients in the USA). In addition, we observed lower rates of APC mutations in Nigerian microsatellite stable patients as well as higher KRAS mutation rates compared to patients at Memorial Sloan Kettering (MSK). Conclusion: Clinical and translational data from high-income countries are likely not applicable to CRC in sub-Saharan African countries. New investigations into the biology and epidemiology of CRC in this region are vital to developing an evidence-based approach to CRC treatment. Our pilot data highlight the importance of characterizing the unique tumor profile of West African patients to tailor treatment options. Furthermore, identifying effective targeted strategies to prevent CRC will be especially crucial to reducing the growing burden of CRC in West Africa given the extremely limited access to early detection via screening in this population. Note: This abstract was not presented at the meeting. Citation Format: Olusegun I. Alatise, Thomas Peter Kingham, African Research Group for Oncology and MSKCC Global Cancer Disparity Initiative team. Colorectal cancer in Nigeria: High tech and low-tech approaches to improving patient outcomes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-327.