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.

The mechanism of cancer resistance to chemotherapy regimen remains uncertain. Colorectal mucinous adenocarcinoma is one of the distinct histological subtypes of the disease implicated in chemotherapeutic resistance associated with nodal and peritoneal metastases and worse disease-free survival as an index of poor prognosis. One of the important acquired capabilities used by the cancer cells to resist anticancer therapies is evasion of apoptosis possibly via inhibitor of apoptosis proteins for which Livin is one. This protein contains baculoviral IAP repeat domains in addition to a RING finger, a protein-protein motif important for binding and inhibition of active caspases that interfere with intrinsic and/or extrinsic pathway and the ensuing blockade of apoptosis. Thus, understanding the molecular events on how cancer cells of mucinous histology evade apoptotic death may provide a novel paradigm for a molecular targeted therapy in the management of colorectal mucinous adenocarcinoma. In this study, the expression pattern and prognostic value of IAP family protein, Livin, in colorectal cancer patients with mucinous histology pre and post-chemotherapy regimen was investigated. Tissue sections from advanced stage colorectal cancer patients who were treated or untreated with neo-adjuvant FOLFOX chemotherapy before curative resection were included in this study. The tissue sections were grouped according to colorectal adenocarcinomas showing mucinous histology and non-mucinous component. Histological study including Haematoxylin and Eosin, and immunohistochemistry for Anti-Livin and DNA mismatched repair proteins were carried out. Immunofluorescence study was performed to clarify the expression pattern of the protein using Anti-Livin antibody. Protein expression quantification study was also used. Results show significant cytoplasmic localisation and expression of Livin protein in the colorectal cancer cells. The Livin protein expression was found to be increased by more than a one-fold post-chemotherapy treatment when compared with pre-chemotherapy treated patients with mucinous histology of colorectal cancer. Younger patients were found to have a greater probability of colorectal mucinous adenocarcinoma diagnosis and worse prognosis. Our findings show that Livin-induced inhibition of apoptosis activity can be a target for novel approaches to treatment and prevention of chemotherapy associated drug resistance in mucinous histology colorectal cancer since Livin overexpression has been associated with metastases and worse disease-free survival. More study is needed Citation Format: Mohammed Faruk, Abdulmumini Hassan Rafindadi, Sani Ibrahim, Surajo Mohammed Aminu, Surajo Mohammed Aminu, Ahmed Adamu, Ahmed Adamu, Yawale Iliyasu, Adamu Abdullahi, Mohammed Sani Shehu, Abdullahi Mohammed, John Idoko, Abdullahi Jibril Randawa, Abdullahi Jibril Randawa, Atara Ntekim, Saad Aliyu Ahmed, Aishatu Suleiman Maude, Almustapha Aliyu Liman, Abubakar Sani, Khalid Zahir Shah, Yahaya Ukwenya, Yahaya Ukwenya, Cheh Augustine Awasum, Kasimu Umar Adoke, James Olowu Enemari, James Olowu Enemari, James Olowu Enemari, Andrew Jonathan Nok. Is Livin a protagonist of mucinous adenocarcinoma histology in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4918. doi:10.1158/1538-7445.AM2017-4918

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.