Grant Details
Grant Number: |
1R01CA246620-01A1 Interpret this number |
Primary Investigator: |
Kingham, T |
Organization: |
Sloan-Kettering Inst Can Research |
Project Title: |
Determining the Risk Factor Profile and Biology of Colorectal Cancer in Nigeria |
Fiscal Year: |
2020 |
Abstract
ABSTRACT
Colorectal cancer (CRC) incidence and mortality are rapidly rising in sub-Saharan Africa; CRC is now the 4th
most common cancer in the World Health Organization-Africa region. This rising burden is mirrored in Nigeria,
where more than half of patients die within one year of diagnosis. These statistics highlight the need for cost-
effective, evidence-based prevention, screening, and treatment interventions in this limited-resource region.
However, an understanding of risk factors and the genomic landscape of CRC in this population is needed to
inform such efforts. Through the African Research Group for Oncology (ARGO), we have established
infrastructure and local scientific partnerships for novel cancer studies in Nigeria. We have an existing clinical
database and a biobank of tumor and matched normal blood specimens from 490 prospectively enrolled Nigerian
CRC patients. Data suggest Nigerian CRCs may possess distinct etiology. Overweight/obesity, the most
common CRC risk factor in the US, is ~3-fold less prevalent in Nigeria. Similarly, other established risk factors,
such as smoking and alcohol use, are half as frequent in Nigeria, suggesting other common endemic factors
(e.g., infectious agents, environment, or diet) may drive CRCs in Nigeria. Furthermore, our pilot sequencing data
from 65 Nigerian tumors show clinically significant differences vs. US patients. For instance, tumors from
Nigerian patients had ~2-fold fewer somatic APC mutations, more KRAS mutations, and ~3-fold higher
prevalence of high microsatellite instability. We also found ~3-fold higher prevalence of hereditary Lynch
syndrome in Nigerian patients. To extend these preliminary analyses and further define CRC etiology in Nigeria,
we propose the first multi-center study of CRC risk factors and genomics in sub-Saharan Africa. We will use
ARGO infrastructure to conduct a large, cost-efficient, opportunistic study to: 1) Identify risk factors for CRC
in Nigeria. We will recruit 600 CRC cases matched to 1,200 cancer-free population-based controls. Participants
will complete an existing questionnaire developed by our group for use in Nigeria to assess demographic,
anthropometric, reproductive, lifestyle, dietary, and medical history. And 2) Characterize molecular features of
CRC tumors in Nigeria. We will perform targeted deep sequencing of 468 established cancer genes in matched
tumor/blood samples from a subset of 360 CRC cases enrolled in Aim 1. After combining with existing data from
65 patients (N=425), we will map cancer genes altered by somatic or germline mutations in Nigerian patients
and compare our data to large existing US datasets. These aims will provide a better understanding of the risk
factor and genomic features of CRC in a West African population – a first step towards improving prevention,
screening, and treatment of the disease in this understudied population. In addition, the etiological insights
gained through the work proposed have high potential applicability to understudied US populations with poor
CRC outcomes, such as African American and early-onset CRC patients.
Publications
Validating a semi-quantitative food frequency questionnaire to assess regional diet in a study of cancer in South West Nigeria.
Authors: Samson M.L.
, Peeri N.C.
, Alatise O.I.
, O'Connell K.
, Sharma A.
, Ogunleye S.G.
, Aderounmu A.A.
, Olasehinde O.
, Ogundokun A.O.
, Ikujenlola A.V.
, et al.
.
Source: Cancer Causes & Control : Ccc, 2023-03-30 00:00:00.0; , .
EPub date: 2023-03-30 00:00:00.0.
PMID: 36995554
Related Citations
Healthcare utilisation, cancer screening and potential barriers to accessing cancer care in rural South West Nigeria: a cross-sectional study.
Authors: Sharma A.
, Alatise O.I.
, O'Connell K.
, Ogunleye S.G.
, Aderounmu A.A.
, Samson M.L.
, Wuraola F.
, Olasehinde O.
, Kingham T.P.
, Du M.
.
Source: Bmj Open, 2021-07-26 00:00:00.0; 11(7), p. e040352.
EPub date: 2021-07-26 00:00:00.0.
PMID: 34312189
Related Citations