High frequency of MLH1 promoter methylation mediated by gender and age in colorectal tumors from Mexican patients

Abstract

Introduction:Several genes determine the development of colorectal cancer (CRC), such as MLH1, which encodes a protein that participates in DNA repair. MLH1 hypermethylation has been associated with gene silencing. Objective: To analyze the methylation of five regions of MLH1 CpG island in colorectal tumors from Mexican patients. Materials and methods: One hundred and one tumor tissue samples were obtained from Mexican patients with CRC who provided informed consent. DNA was subjected to bisulfite conversion. Methylation of all five regions of the CpG island was evaluated using methylation-specific PCR. Results: The frequency of methylation in Mexican patients with CRC was 25%. Regions A and B methylation was the main observed pattern (60%). Female patients showed a higher frequency of methylation (71%; OR: 3.085; CI: 1.85-8.03; p = 0.02), and out of total methylated samples, 80% corresponded to individuals older than 45 years (p < 0.05). Conclusion: We calculated a methylation frequency for the MLH1 gene of 25% in Mexican patients with CRC, with this being the first report for this population. Female patients and patients older than 45 years showed a higher frequency of methylation.

Clinicopathological features and prognoses in younger and older patients with mismatch repair defects colorectal cancer: a retrospective comparative cohort study

“…No previous studies had been conducted on the relationship between MSI-H tumors and age. A large sample study of unresectable or metastatic solid tumors in Japan examined the proportion of MSI-H in all tumors and found that the proportion was higher in patients aged less than 40 years than those aged over 80 years ( 7 ) The reason for the high proportion of MSI-H in patients aged over 80 years may be related to the occurrence of MLH1 promoter methylation ( 8 ). The high proportion of MSI-H in young patients may be related to genetic factors, and it is possible that these patients have Lynch syndrome or dMMR syndrome ( 9 , 10 ).…”

Obesity-Associated Differentially Methylated Regions in Colon Cancer

“…Whether the methylation threshold is purely statistical using p values, or if it is a differential change measured in a percent difference, has not yet been sufficiently documented or validated. Many studies focus on single-gene associations with methylated CpG or DMR, some taking clinical data into context [ 67 , 68 ]. The genomic region of DMR and the impact on gene expression has also been studied, showing that DMRs on promoter regions adversely affect gene function [ 38 , 39 ].…”