PURPOSE Colorectal cancer (CRC) incidence rates are increasing among individuals < 50 years of age (early-onset CRC) globally with causes unknown. Racial/ethnic disparities in early-onset CRC have also grown more pronounced, because Black individuals have higher early-onset CRC incidence and poorer survival compared with White individuals. We describe the prevalence and burden of early-onset CRC among Africans in Nigeria and African Americans (AAs) in the United States. PATIENTS AND METHODS We identified Black individuals diagnosed with a first primary CRC ages 18 to 49 years between 1989 and 2017 at Ahmadu Bello University Teaching Hospital in Zaria, Nigeria (Nigerians), and in the United States (AAs) using the National Institutes of Health/National Cancer Institute’s SEER program of cancer registries. Multivariable logistic regression models were used to investigate clinical and demographic differences between Nigerians and AAs with early-onset CRC, adjusted for age, sex, tumor site, and histology. RESULTS A total of 5,019 Black individuals were diagnosed with early-onset CRC over the study period (379 Nigerians; 4,640 AAs). Overall, approximately one third of young Black patients were diagnosed with rectal tumors (35.8%). Nigerian individuals with early-onset CRC were eight-fold more likely to be diagnosed with rectal tumors (odds ratio [OR], 8.14; 95% CI, 6.23 to 10.62; P < .0001) and more likely to be diagnosed at younger ages (OR, 0.87; 95% CI, 0.86 to 0.89; P < .0001) compared with young African Americans in adjusted models. CONCLUSION Compared with AA individuals diagnosed with early-onset CRC, Nigerian individuals harbor distinct features of early-onset CRC. Additional investigation of the histopathologic and biologic heterogeneity of early-onset CRCs among Black individuals is critical for understanding racial disparities in susceptibility and outcomes, which may have implications for tailored early-onset CRC prevention, detection, and treatment strategies.

Evasion of apoptosis is associated with treatment resistance and metastasis in colorectal cancer (CRC). Various cellular processes are associated with evasion of apoptosis. These include overexpression of pro-apoptotic proteins (including p53 and PD-L1), anti-apoptotic proteins (BIRC7/Livin and Bcl-2), chemokine receptors (including DARC), and dysregulation of DNA mismatch repair proteins (including MSH2 and PMS2). The aim of this study was to determine the effect of folinic acid, 5-FU and oxaliplatin (FOLFOX) as a single agent and aspirin plus FOLFOX in various combinations on the aforementioned proteins in human CRC, SW480 cell line and rat models of N-Methyl-N-Nitrosourea (NMU)-induced CRC. In addition, effects of the NMU-induced CRC and chemotherapeutic regimens on haematological and biochemical parameters in the rat models were studied. Immunohistochemistry, immunofluorescence and immunoblot techniques were used to study the expression pattern of the related proteins in the human CRC cells pre- and post-treatment. Double contrast barium enema, post-mortem examination and histological analyses were used to confirm tumour growth and the effect of the treatment in vivo in rat models. Notably, we found in human mucinous CRC, a significant increase in expression of the BIRC7/Livin post-FOLFOX treatment compared with pre-treatment (p = 0.0001). This increase provides new insights into the prognostic role of BIRC7/Livin in evasion of apoptosis and facilitation of treatment resistance, local recurrence and metastasis particularly among mucinous CRCs post-FOLFOX chemotherapy. These poor prognostic features in the CRC may be further compounded by the significant suppression of DARC, PD-L1, PMS2 and overexpression of MSH2 and anti-apoptotic Bcl-2 and p53 proteins observed in our study (p < 0.05). Importantly, we found a significant reduction in expression of BIRC7/Livin and reactivation of DARC and PD-L1 with a surge in Annexin V expression in rat models of CRC cells post-treatment with a sequential dose of aspirin plus FOLFOX compared with other treatments in vivo (p <0.05). The mechanistic rational of these effects underscores the importance of expanded concept of possible aspirin combination therapy with FOLFOX sequentially in future CRC management. Validation of our findings through randomized clinical trials of aspirin plus FOLFOX sequentially in patients with CRC is therefore warranted.

Cancer ranks as a leading cause of death and an important barrier to increasing life expectancy worldwide. Globally, there are estimated 19.3 million new cancer cases and about 10 million cancer mortality in 2020. Should current cancer trends continue, Africa’s cancer burden is projected to reach an alarming 1.4 million new cases and 1 million deaths by 2030. Thus, racial/ethnic disparities in cancer morbidity and mortality continue to widen globally but molecular biology and genomic studies rarely interrogate cancer in diverse disadvantaged populations. Effective control of tumour growth in cancer microenvironment is facilitated by cellular interaction between innate and adaptive immune cells. The programmed death ligand-1 (PD-L1), an immune checkpoint expressed on tumour cells, facilitates the escape of immunosurveillance in cancer by interacting with programmed death-1 (PD-1) to initiate apoptosis of the immune cells. The interaction between these immune cells may be mediated by atypical chemokine receptor 1 (ACKR1)/Duffy antigen receptor for chemokines (DARC) towards activation of tumour-specific immune response by chemoattraction of leukocytes to the inflammatory sites. Livin/BIRC7 protein overexpression is a key component of evasion of apoptosis in cancer cells. Interestingly, Annexin A5, an important member of Annexin family of proteins with high affinity to phosphatidylserine, has been reported to serve as an important component of apoptosis by stimulating immunogenicity of tumor cells. In this pilot study, we report using immunohistochemistry, RNA-seq and whole exome sequencing the expression pattern and functional significance of PD-L1, ACKR/DARC, Livin/BIRC7 and Annexin A5 in malignant tumours of the bone, prostate, breast, eye/orbit, nasopharynx, and metastatic carcinomas to the brain, neck and lymph node among West Africans in Zaria, Nigeria. In osteosarcoma and osteogenic sarcoma of the bone, we observed negative expression of ACKR/DARC and PD-L1, and overexpression of Livin and Annexin A5 proteins. However, a mucoepidermoid carcinoma of the index finger shows strong expression of ACKR/DARC, PD-L1 and Annexin A5 with poor expression of Livin protein. The results also show negative expression of ACKR/DARC, PD-L1 and Livin proteins from retinoblastoma, nasopharyngeal carcinoma, metastatic adenosquamous carcinoma to the parietal lobe of the brain, Metastatic squamous neck cancer, metastatic carcinoma of the lymph nodes and invasive breast carcinoma no special type (NST) grade 3. Prostate adenocarcinomas with Gleason grade 9 show negative expression of ACKR/DARC and PD-L1 proteins. All the tumours studied are strongly positive for Annexin A5 expression. The diverse expression pattern of ACKR/DARC, PD-L1, Livin and Annexin A5 in malignant tumours of the bone, retina, nasopharynx, breast, prostate and metastatic carcinomas to the brain, neck and lymph may be of significant importance in tumour behaviour and prognosis. Citation Format: Faruk Mohammed, Melissa B. Davis, Clayton C. Yates, Halimatu Sadiya Musa. The role of PD-L1, ACKR/DARC, Livin and Annexin A5 in malignant tumours of the bone, prostate, breast, eye/orbit, nasopharynx, and metastatic carcinomas to the brain, neck and lymph node among West Africans in Zaria, Nigeria [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C050.

Colorectal cancer incidence rates are rising among individuals age younger than 50 years (early-onset CRC) globally with causes unknown. Racial and ethnic disparities in early-onset CRC have also grown more pronounced, as blacks have higher early- onset CRC incidence and poorer survival compared with whites. We described the prevalence and burden of early-onset CRC among Africans in Nigeria and African Americans in the United States. We identified black individuals diagnosed with a first primary colorectal cancer ages 18 to 49 years between 1989 and 2017 at Ahmadu Bello University Teaching Hospital in Zaria, Nigeria using the Zaria Cancer Registry (Nigerians), and from population-based cancer registries across the US (African Americans) using the NIH/NCI’s Surveillance, Epidemiology, and End Results (SEER) program. Multivariable logistic regression models were used to investigate clinicopathologic and demographic differences between Nigerians and African Americans with early-onset CRC adjusted for age, sex, tumor site and grade. A total 566 and 31,284 colorectal adenocarcinoma cases were diagnosed among Nigerians and African Americans, respectively, in hospitals and clinics over the 28-year study period. More than 60% of Nigerian patients (n=354) were diagnosed with early-onset CRC. In contrast, one out of every 8 (12.5%) African Americans were diagnosed with CRC before age 50 years (n=3,898; P&lt;0.0001). Subsequent analyses focused on the subset of this population diagnosed with early-onset CRC, which included 4,252 black individuals (354 Nigerian and 3,898 African American patients). Overall, approximately one-third of young black patients were diagnosed with rectal tumors (30.8%). Nigerians with early-onset CRC were more likely to be male compared to African American patients (57.9% vs 49.1%; P=0.001). Among African Americans, one quarter of early-onset cases were diagnosed with cancers of the rectum (26.5%), whereas 77.4% of young Nigerian patients were diagnosed with rectal tumors (P&lt;0.0001). Nigerian individuals with early-onset CRC were 10-fold more likely to be diagnosed with rectal cancers (OR=10.35, 95%CI=7.14-14.99, P&lt;0.001) and more likely to be diagnosed at younger ages (OR=0.87, 95%CI=0.85-0.89, P&lt;0.001) compared with young African Americans. Young Nigerians with CRC were also 61% less likely to be diagnosed with high-grade (grade III/IV) tumors compared to African Americans with early-onset CRC (OR 0.39, 95%CI 0.23-0.67, P=0.001). This international cohort study reveals distinct patterns of early-onset CRC among black patients, as Nigerians were more likely to be diagnosed with rectal tumors and at younger ages compared with African Americans. Further investigation of the clinical and biological heterogeneity of early-onset CRCs among blacks is ongoing, and critical for understanding global cancer disparities in disease susceptibility and outcomes–which may have implications for tailored early-onset CRC prevention, detection and treatment strategies. Citation Format: Andreana N. Holowatyj, Aishatu Suleiman Maude, Halimatu Sadiya Musa, Ahmed Adamu, Sani Ibrahim, Adamu Abdullahi, Muhammad Manko, Sirajo Mohammed Aminu, Abdullahi Mohammed, John Idoko, Yahaya Ukwenya, John Carpten, Paulette D. Chandler, Heather Hampel, Faruk Mohammed. Distinct patterns of early-onset colorectal cancer among Nigerians and African Americans: An international cohort study [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-191.