Differences in K-rasand mitochondrial DNA mutations and microsatellite instability between colorectal cancers of Vietnamese and Japanese patients

Abstract

BackgroundThe incidence of early-onset (under 50 years of age) colorectal cancer (CRC) in the Vietnamese has been reported to be quite higher than that in the Japanese. To clarify the differences in genetic alterations between Vietnamese and Japanese CRCs, we investigated mutations in K-ras and mitochondrial DNA (mtDNA) and high-frequency microsatellite instability (MSI-H) in the CRCs of Vietnamese and Japanese patients.MethodsWe enrolled 60 Vietnamese and 233 Japanese patients with invasive CRCs. DNA was extracted from formalin-fixed, paraffin-embedded tissue sections. K-ras mutations were examined with PCR-single-strand conformation polymorphism analysis. mtDNA mutations and MSI-H were examined with microsatellite analysis using D310 and BAT-26, respectively.ResultsK-ras mutations were examined in 60 Vietnamese and 45 Japanese CRCs. The frequency of the mutations in the Vietnamese CRCs was significantly higher than that in the Japanese CRCs (8 of 24 [33%] vs 5 of 45 [11%], p =0.048). MSI-H was examined in 60 Vietnamese and 130 Japanese CRCs. The frequency of MSI-H in the Vietnamese CRCs was also significantly higher than that in the Japanese CRCs (6 of 27 [22%] vs 10 of 130 [8%], p =0.030). mtDNA mutations were examined in 60 Vietnamese and 138 Japanese CRCs. The frequency of mtDNA mutations in the Vietnamese CRCs was significantly higher than that in the Japanese CRCs (19 of 44 [43%] vs 11 of 133 [9%], p <0.001). There were no significant differences in clinicopathologic characteristics, such as age, sex, tumour location, and depth, in terms of tumours with/without each genetic alteration in the CRCs of the Vietnamese and Japanese patients.ConclusionsThese results indicate that the developmental pathways of CRCs in the Vietnamese may differ from those of CRCs in the Japanese.

High Copy Number of Mitochondrial DNA Predicts Poor Prognosis in Patients with Advanced Stage Colon Cancer

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“…There have been a few reports about mtDNA in colon cancer, reaching different conclusions. Most of them tried to elucidate the mechanism of aberrant mtDNA copy content in colon cancer (15)(16)(17), genetic changes in mtDNA (18), and the relevant single nucleotide polymorphism (19). Thyagarajan's group tested the mtDNA copy content in peripheral blood of colorectal cancer patients and controls free of colorectal cancer, and found a U-shaped correlation between the relative mtDNA copy number and the colorectal cancer risk (20).…”

Comprehensive Analysis of the Relationship Between RAS and RAF Mutations and MSI Status of Colorectal Cancer in Northeastern China

“…In the United States, only a few studies demonstrated a higher mutation rate of RAF [15][16][17]45]. In Asia, the mutation rate is the lowest, ranging between 4-9% [24][25][26][27][28][45][46][47].…”

Asia‐Pacific Colorectal Screening score: A useful tool to stratify risk for colorectal advanced neoplasms in Vietnamese patients with irritable bowel syndrome

“…Although the reasons have not been clearly understood, one study from our group, which compared Vietnamese CRC with Japanese CRC, showed that the frequencies of K‐ras gene mutations, mitochondrial DNA mutations, and high‐frequency of genetic microsatellite instability in the Vietnamese CRC were significantly higher. This suggests different developmental pathways of CRC in the Vietnamese from those in the Japanese . An important point in clinical practice is that both of the patients with early‐onset CRC in our study had a 2‐year history of IBS symptoms, and alarm features were only detected later on.…”