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Molecular signature and MMR status of early- and late-onset colorectal cancer among Arabs
Background
Early-onset colorectal cancer (EO-CRC) is increasing in alarming pace globally. Ethnical/ racial disparities in the EOCRC clinicopathological and molecular signatures have been reported from different geographical regions. There is scarce data about the status and molecular features of the disease among Arabs despite the noticable increasing incidence. The aim of this study is to describe the clinicopathological parameters, molecular signatures and MMR status of early and late onset CRC among Arab patients. Then we compare these findings with finding from other ethnic groups reported from other geographical regions.
Methods
This is a retrospective cohort study that included patients with pathologically confirmed colorectal cancer treated between 2015-2021 in Sultan Qaboos University Hospital, Oman. Data were collected from electronic health records. Clinicopathological data along with MMR status, KRAS and BRAF data were collected. EOCRC was defined as CRC at = 50years old. Clinicopathological and molecular features were compared between EOCRC and LOCRC and then compared with published data from other ethnic groups.
Results
Of 254 patients diagnosed with CRC, 80 (31.5 %) had EOCRC. Gender, stage, and tumor sidedness were similar between the EOCRC and LOCRC groups. Male gender was dominant (55%) among both groups. Adenocarcinoma was the most common type among EOCRC (58, 72.5%) and LOCRC (127, 73%) followed by signet (8.7% and 1.1%) which was significantly different (p = 0.01). Forty of EOCRC patients (50%) presented with advanced metastatic stage compared to 76 (43.6%) of LOCRC (P = .038). There is no difference in tumor sidedness in both groups where majority (77% of EOCRC, 76% of LOCRC) of patients presented with left sided tumor (P = 0.1). Rectum was involved in 38 (46.5%) of EOCRC and 74 (42.5%) of LOCRC. All 4 MMR proteins were expressed in 57 (71%) of EOCRC and 107 (61%) of LOCRC cases, where they were classified as MMR proficient (pMMR). Nine patients from the LOCRC group and five from the EOCRC group had one or more abnormal MMR proteins and were classified as MMR deficient (dMMR). Three of them are suspicious of having Lynch syndrome since they have a wild-type BRAF as well. The remaining had loss of both MLH1 and PMS2. KRAS status was checked for 105 patients (64 LOCRC and 41 EOCRC). Thirty-eight (21.8%) of LOCRC and 16 (20%) of EOCRC are wild KRAS type. Compared with reported findings from other geographhical regions, this data did not show a significant differnece between EOCRC and LOCRC at the clinicopathological and molecular level.
Conclusions
EOCRC and LOCRC among Arabs are almost similar in term of clinicopathological and molecular signatures. Studies from other geographical regions reported distinct features that differentiate the two entities which was not obvious in this study. More studies are needed to correlate these clinicopathological and molecular signatures with patients' outcome and type of management received. Subsequently, specific molecular studies tailored to different racial/ethnic group would be the way to understand and tackle this alarming increase in EOCRC incidence.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosures
A. AlMirza: Research grant / Funding (institution): Sultan Qaboos university . All other authors have declared no conflicts of interest.
