Molecular and phenotypic profiling of colorectal cancer patients in West Africa reveals biological insights

Alatise, Olusegun Isaac; Knapp, Gregory C; Sharma, Avinash; Chatila, Walid K.; Arowolo, Olukayode; Olasehinde, Olalekan; Famurewa, O.; Omisore, Adeleye Dorcas; Komolafe, Akinwumi Oluwole; Olaofe, Olaejirinde Olaniyi; Katung, Aba; Ibikunle, David Eyitayo; Egberongbe, Adedeji A.; Olatoke, Samuel; Agodirin, SO; Adesiyun, O A M; Adeyeye, Ademola; Kolawole, Oladapo; Olakanmi, Akinwumi O.; Arora, Kanika; Constable, Jeremy; Shah, Ronak; Basunia, Azfar; Sylvester, Brooke E.; Wu, Chao; Weiser, Martin R.; Seier, Ken; Gönen, Mithat; Stadler, Zsofia K.; Kemel, Yelena; Vakiani, Efsevia; Berger, Michael F.; Chan, Timothy A.; Solit, David B.; Shia, Jinru; Sánchez-Vega, Francisco; Schultz, Nikolaus; Brennan, Murray F.; Smith, J. Joshua; Kingham, T. Peter

doi:10.1038/s41467-021-27106-w

Cited by 29 publications

(39 citation statements)

References 33 publications

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“…Only three studies in sub-Saharan Africa have attempted to further differentiate between subgroups within the overarching category of MSI tumours. Alatise et al found the rate of MSI in their Nigerian cohort to be more than double that reported in HIC 13. However, germline testing on a subset of the cases found pathogenic mutations to be present in only 17% of the MSI-H cases, which is similar to internationally reported rates (11–18.5%) 39 48.…”

Section: Crc In Africasupporting

confidence: 57%

“…These include a younger age of onset, more advanced disease at presentation, increased mucinous differentiation and increased frequency of microsatellite instability (MSI). More recently, larger studies have shown an increased frequency of left-sided tumours among young indigenous Africans 12 13. This is in contrast to data from Europe, Japan and the USA, which shows decreasing frequency of left-sided disease 14–16…”

Section: Introductionmentioning

confidence: 89%

“…Most of these studies are descriptive and have focused on the clinicopathological characteristics, and to a lesser extent,the prevalence of MSI tumours. To our knowledge, there has only been one study in sub-Saharan Africa that has extensively interrogated the genetic basis of CRC in a cohort of unselected Nigerian patients 13. This represents an obvious knowledge gap.…”

Section: Crc In Africamentioning

confidence: 99%

“…Holla et al recently examined a cohort of 27 indigenous African patients with CRC and found that MMR-proficient tumours occurred at a significantly younger age (44 vs 35 years) and showed a predominance for the distal colon (73%) 37. Other studies with larger sample sizes have, however, found an older age of onset for MMR-proficient tumours 13 34. McCabe et al described a greater proportion of dMSH2/6 (49%) in black patients compared with other ethnic groups who predominantly showed a dMLH1/PMS2 pattern 34.…”

Section: Crc In Africamentioning

confidence: 99%

“…Studies using IHC and PCR-based methods to detect MSI in Nigeria reported the frequency of MSI to be 23–43% 7 42 43. Alatise et al recently published work on a Nigerian cohort, which likely represents the most sophisticated study to date in sub-Saharan Africa 13. They used a hybrid approach to determine MSI status including MSIsensor (NGS data) and MMR IHC and found the rate of MSI to be 28.1% (18/64) and 21.3% (20/94), respectively.…”

Section: Crc In Africamentioning

confidence: 99%

See 4 more Smart Citations

Genomic landscape of colorectal carcinoma in sub-Saharan Africa

et al. 2022

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Our understanding of the molecular classification of colorectal carcinoma (CRC) has evolved significantly over the past two decades. Tumours can be broadly categorised as microsatellite stable (MSS), microsatellite instability (MSI) or CpG island-methylator phenotype. Prognostic and predictive information is provided by these categories. The overwhelming majority of the data on which these categories are based have originated from Europe and North America. There is a dearth of information represented from Africa and indigenous African patients. However, some small studies and preliminary data have shown significant differences in all of these groups. The prevalence of MSI in Africa is consistently reported as almost double that of European and North American data. Interestingly, BRAF V600E mutations and MLH1 promotor hypermethylation seem to be uncommon in Africa. The high proportion of MSI tumours is only partly accounted for by germline mutations in mismatch repair genes (Lynch syndrome), suggesting that there are likely to be other mechanisms at play. Within the MSS group, preliminary data suggest that the typical molecular pathways (Wingless/Integrated pathway activation) may not be as dominant in Africa. The purpose of this review is to summarise the current state of the molecular genetic landscape of CRC in Africa and provide insights into areas for further study.

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Section: Crc In Africasupporting

confidence: 57%

Section: Introductionmentioning

confidence: 89%

Section: Crc In Africamentioning

confidence: 99%

Section: Crc In Africamentioning

confidence: 99%

Section: Crc In Africamentioning

confidence: 99%

See 3 more Smart Citations

Genomic landscape of colorectal carcinoma in sub-Saharan Africa

et al. 2022

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A tale of two pathways: Review of immune checkpoint inhibitors in DNA mismatch repair‐deficient and microsatellite instability‐high endometrial cancers

Liu,

Weigelt

2024

Cancer

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The DNA mismatch repair (MMR) pathway is critical for correcting DNA mismatches generated during DNA replication. MMR‐deficiency (MMR‐D) leads to microsatellite instability (MSI) associated with an increased mutation rate, driving cancer development. This is particularly relevant in endometrial cancer (EC) as 25%–30% of tumors are of MMR‐D/MSI‐high (MSI‐H) phenotype. Comprehensive assessment using immunohistochemistry (IHC) and sequencing‐based techniques are necessary to fully evaluate ECs given the importance of molecular subtyping in staging and prognosis. This also influences treatment selection as clinical trials have demonstrated survival benefits for immune checkpoint inhibitors (ICIs) alone and in combination with chemotherapy for MMR‐D/MSI‐H EC patients in various treatment settings. As a portion of MMR‐D/MSI‐H ECs are driven by Lynch syndrome, an inherited cancer predisposition syndrome that is also associated with colorectal cancer, this molecular subtype also prompts germline assessment that can affect at‐risk family members. Additionally, heterogeneity in the tumor immune microenvironment and tumor mutation burden (TMB) have been described by MMR mechanism, meaning MLH1 promoter hypermethylation versus germline/somatic MMR gene mutation, and this may affect response to ICI therapies. Variations by ancestry in prevalence and mechanism of MMR‐D/MSI‐H tumors have also been reported and may influence health disparities given observed differences in tumors of Black compared to White patients which may affect ICI eligibility. These observations highlight the need for additional prospective studies to evaluate the nuances regarding MMR‐D heterogeneity as well as markers of resistance to inform future trials of combination therapies to further improve outcomes for patients with EC.

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Age at diagnosis for lung, colon, breast and prostate cancers: An international comparative study

Zahed,

Feng,

Sheikh

et al. 2023

Intl Journal of Cancer

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Differences in the average age at cancer diagnosis are observed across countries. We therefore aimed to assess international variation in the median age at diagnosis of common cancers worldwide, after adjusting for differences in population age structure. We used IARC's Cancer Incidence in Five Continents (CI5) Volume XI database, comprising cancer diagnoses between 2008 and 2012 from population‐based cancer registries in 65 countries. We calculated crude median ages at diagnosis for lung, colon, breast and prostate cancers in each country, then adjusted for population age differences using indirect standardization. We showed that median ages at diagnosis changed by up to 10 years after standardization, typically increasing in low‐ and middle‐income countries (LMICs) and decreasing in high‐income countries (HICs), given relatively younger and older populations, respectively. After standardization, the range of ages at diagnosis was 12 years for lung cancer (median age 61‐Bulgaria vs 73‐Bahrain), 12 years for colon cancer (60‐the Islamic Republic of Iran vs 72‐Peru), 10 years for female breast cancer (49‐Algeria, the Islamic Republic of Iran, Republic of Korea vs 59‐USA and others) and 10 years for prostate cancer (65‐USA, Lithuania vs 75‐Philippines). Compared to HICs, populations in LMICs were diagnosed with colon cancer at younger ages but with prostate cancer at older ages (both pLMICS‐vs‐HICs < 0.001). In countries with higher smoking prevalence, lung cancers were diagnosed at younger ages in both women and men (both pcorr < 0.001). Female breast cancer tended to be diagnosed at younger ages in East Asia, the Middle East and Africa. Our findings suggest that the differences in median ages at cancer diagnosis worldwide likely reflect population‐level variation in risk factors and cancer control measures, including screening.

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Molecular and phenotypic profiling of colorectal cancer patients in West Africa reveals biological insights

Cited by 29 publications

References 33 publications

Genomic landscape of colorectal carcinoma in sub-Saharan Africa

Genomic landscape of colorectal carcinoma in sub-Saharan Africa

A tale of two pathways: Review of immune checkpoint inhibitors in DNA mismatch repair‐deficient and microsatellite instability‐high endometrial cancers

Age at diagnosis for lung, colon, breast and prostate cancers: An international comparative study

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