A single nucleotide polymorphism (SNP) in the CpG island of <i>MLH1</i> (<i>MLH1</i>-93G>A or rs1800734) is associated with CpG island hypermethylation and decreased <i>MLH1</i> expression in CRC tumours.
The -93G > A (rs1800734) polymorphism within the core promoter region of the MutL homolog 1 (MLH1) gene has recently been proposed as a low penetrance variant for colorectal cancer (CRC).
Our results suggest an influence of MLH1 promoter polymorphism -93G>A in modulating susceptibility risk in Malaysian CRC patients, especially those with sporadic disease.
Among case patients from Ontario, an association between the MLH1 -93G>A polymorphism and a strong family history of colorectal cancer (for Amsterdam criteria I and II, P = .004 and P = .02, respectively) was observed.
In relation to the more frequent 655A-->G polymorphism, association analyses revealed that G carriers (AG or GG genotype) displayed a higher risk of CRC compared with AA homozygous [odds ratio (OR) AG=2.55, 95% confidence interval (CI)=1.48-4.39; P=0.01 and OR GG=2.48, 95% CI=1.20-5.11; P=0.01, respectively].
The G allele of rs1799977 polymorphism was proved to connect with susceptibility of colorectal cancer (allele model: OR = 1.21, P = 0.023; dominate model: OR = 1.32, P <0.0001) and prostate cancer (dominate model: OR = 1.36, P <0.0001).
Four single nucleotide polymorphisms in 3 mismatch repair genes (MSH3 R940Q, MSH3 T1036A, MSH6 G39E and MLH1 I219V) were genotyped in 237 colorectal cancer cases and a subcohort of 2,189 participants.
This screen identifies the A-allele of rs1800734 within the promoter region of MLH1 as perturbing the binding of TFAP4 and consequently increasing DCLK3 expression through a long-range interaction, which promotes cancermalignancy through enhancing expression of the genes related to epithelial-to-mesenchymal transition.
We hypothesised that a common substitution in the basal promoter of MLH1 (position -93, rs1800734) modifies the risk of cancer after methylating chemotherapy.
The -93G>A (rs1800734) polymorphism located in the promoter of mismatch repair gene, MLH1, has been identified as a low-penetrance variant for cancer risk.
In the subgroup analysis by cancer type, we found a moderate association between rs1800734 and the risk of gastric cancer (allele model: OR = 1.14, P = 0.017; homozygote model: OR = 1.33, P = 0.019; dominant model: OR = 1.27, P = 0.024) and lung cancer in recessive model (OR = 1.27, P = 0.024).
Methylenetetrahydrofolate reductase C677T genotype affects promoter methylation of tumor-specific genes in sporadic colorectal cancer through an interaction with folate/vitamin B12 status.
Females who were heterozygous or homozygous for the C677T MTHFR polymorphism were at increased risk of developing CIMP+ CRC (odds ratio 2.17, 95% confidence interval 1.03-4.57; p=0.037).
The diversity of the Mediterranean diet and the heterogeneity of acquired epigenetic alterations in colorectal cancer (CRC) led us to examine the possible association between dietary factors and promoter hypermethylation in genes implicated in the pathogenesis of these neoplasms (p16(INK4a), p14(ARF), hMLH1) and the interaction with methylene tetrahydrofolate reductase (MTHFR) C677T polymorphism.