Colorectal Carcinoma in Malaysians: DNA Mismatch Repair Pattern in a Multiethnic Population

Cheah, Phaik‐Leng; Looi, Lai‐Meng; Teoh, Kean-Hooi; Rahman, Nazarina Abdul; Wong, Li-Xuan; Tan, Soo‐Yong

doi:10.7314/apjcp.2014.15.7.3287

Cited by 7 publications

(4 citation statements)

References 32 publications

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“…MMR protein loss is more commonly seen in right sided tumours compared to left sided and rectal tumours as was evident in this series as well. This is similar to studies from other parts of the world, [24][25][26]29 however, Ravikanth et al 30 reported MSI-H status to be present most commonly in rectal cancer (66%).…”

Section: Discussionsupporting

confidence: 87%

Pattern of mismatch repair protein loss and its clinicopathological correlation in colorectal cancer in North India

et al. 2018

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Background: To determine the mismatch repair (MMR) protein loss in colorectal cancer (CRC) in north Indian patients and its clinicopathological correlation. Methods: A prospective study on patients with colorectal cancer from a tertiary level hospital conducted between May 2014 and June 2015. MMR protein loss was determined using immunohistochemistry for MLH1, MSH2, PMS2 and MSH6. Results: 52 patients (38 male and 14 females) of CRC, with median age of 52.5 years who underwent resection form the study group. 18 (35%) patients were < 50 years of age. Family history of malignancy was present in 3 (6 %) patients. A total of 15 (29%) patients had loss of MMR protein of which 7 (46%) were < 50 years. Most common MMR loss was combined loss of MSH2 + MSH6 [6 (11.5%)] followed by isolated loss of PMS2 [5 (9.6%)]. MMR protein loss was more frequent in patients with right side colon cancer [12 (42%)] compared to left [3 (13%)] (p = 0.033). MMR protein loss was seen in 11 (34%) out of 32 patients fulfilling the revised Bethesda criteria compared to 4 (20%) out of 20 patients who did not fulfil the criteria (p = 0.352). Conclusion: This study demonstrates high frequency of MMR protein loss in colorectal cancer in north Indian patients which was more common in right colon cancer. Many patients having MMR protein loss do not satisfy the revised Bethesda criteria and would have been missed if selective testing was done. Further research and larger studies are required to validate these findings and develop India specific clinical criteria.

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Section: Discussionsupporting

confidence: 87%

Pattern of mismatch repair protein loss and its clinicopathological correlation in colorectal cancer in North India

et al. 2018

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“…However, dMMR patients accounted for less than 20% of CRC cases, representing only a small proportion of patients who benefit from immunotherapy. In the present study, we found the ratio of CRC patients with dMMR status was 12.61% (29/230), which was lower than the results of the Malaysia and India population (14.8%) ( Cheah et al, 2014 ), but higher than the reports of the Hispanic population from Puerto Rico (10.24%) ( De Jesus-Monge et al, 2010 ), the Mashhad population (10.25%) ( Goshayeshi et al, 2017 ) and the Fujian population in Southeast China ( Ye et al, 2015 ). These findings indicate that the proportion of dMMR in CRC varies by country and race.…”

Section: Discussioncontrasting

confidence: 79%

Gut microbiota distinct between colorectal cancers with deficient and proficient mismatch repair: A study of 230 CRC patients

Jin

Shi

et al. 2022

Front. Microbiol.

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Colorectal cancers (CRCs) with deficient DNA mismatch repair (dMMR) and proficient DNA mismatch repair (pMMR) exhibit heterogeneous tumor characteristics, distinct responses to immunotherapy, and different survival outcomes. However, it is unclear whether gut microbiota is distinct between CRCs with different MMR status. In this study, we used immunohistochemistry for four major MMR proteins to determine the MMR status in 230 CRC patients. The gut microbiota was profiled in cancerous and adjacent normal tissues by using bacterial 16S rRNA sequencing. The differences in microbiota diversity, composition and related metabolic pathways between patients with dMMR and pMMR CRCs were explored. Linear discriminant analysis effect size (LEfSe) analysis was further applied to validate the significant taxonomic differences at the genus level. In our study cohort, dMMR status was identified in 29 of 230 (12.61%) tumors. The richness (alpha-diversity) of gut microbiome in dMMR tumor tissue was higher compared with pMMR tumor tissues. The microbial community composition (beta-diversity) between the two groups was significantly different. The dMMR group was enriched considerably for some microbiota, including Fusobacteria, Firmicutes, Verrucomicrobia, and Actinobacteria at the phylum level and Fusobacterium, Akkermansia, Bifidobacterium, Faecalibacterium, Streptococcus, and Prevotella bacteria at the genus level. However, the pMMR group was dominated by Proteobacteria at the phylum level and Serratia, Cupriavidus and Sphingobium at the genus level. Moreover, a wide variety of microbiota associated functional pathways were observed with different MMR status. KEGG pathway analysis indicated a higher abundance of the biosynthesis and metabolic pathways of glycan and nucleotide, cell growth and death pathways, genetic replication and repair pathways in dMMR samples compared with the pMMR group. These findings demonstrate that CRC patients with different MMR status have distinct gut bacterial community richness, compositions and related metabolic pathways, suggesting basis that may explain the effectiveness of immunotherapy in dMMR tumors.

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“…Colorectal cancer continues to afflict several thousands of males and females per year, accounting for about 10% of cancer-related deaths and weighed as the third commonest malignancy in Malaysia as reported in 2007 [1] . Therapeutic modalities such as chemotherapy and radical colostomy are considered curative for localized manageable cases, in fact they are acknowledged for the noticed increase in the five-year survival [2] .…”

Section: Introductionmentioning

confidence: 99%

Chemopreventive Efficacy of Andrographis paniculata on Azoxymethane-Induced Aberrant Colon Crypt Foci In Vivo

et al. 2014

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Andrographis paniculata is a grass-shaped medicinal herb, traditionally used in Southeast Asia. The aim of this study was to evaluate the chemoprotective effects of A. paniculata on colorectal cancer. A. paniculata ethanol extract was tested on azoxymethane (AOM)-induced aberrant crypt foci (ACF) in vivo and in vitro. A. paniculata treated groups showed a significant reduction in the number of ACF of the treated rats. Microscopically, ACF showed remarkably elongated and stratified cells, and depletion of the submucosal glands of AOM group compared to the treated groups. Histologically, staining showed slightly elevated masses above the surrounding mucosa with oval or slit-like orifices. Immunohistochemically, expression of proliferating cell nuclear antigen (PCNA) and β-catenin protein were down-regulated in the A. paniculata treated groups compared to the AOM group. When colon tissue was homogenized, malondialdehyde (MDA) and nitric oxide (NO) levels were significantly decreased, whereas superoxide dismutase (SOD) activity was increased in the treated groups compared to the AOM group. A. paniculata ethanol extract showed antioxidant and free radical scavenging activity, as elucidated by the measure of oxidative stress markers. Further, the active fractions were assessed against cell lines of CCD841 and HT29 colon cancer cells.

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Colorectal Carcinoma in Malaysians: DNA Mismatch Repair Pattern in a Multiethnic Population

Cited by 7 publications

References 32 publications

Pattern of mismatch repair protein loss and its clinicopathological correlation in colorectal cancer in North India

Pattern of mismatch repair protein loss and its clinicopathological correlation in colorectal cancer in North India

Gut microbiota distinct between colorectal cancers with deficient and proficient mismatch repair: A study of 230 CRC patients

Chemopreventive Efficacy of Andrographis paniculata on Azoxymethane-Induced Aberrant Colon Crypt Foci In Vivo

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