Methylenetetrahydrofolate reductase C677T genotype affects promoter methylation of tumor-specific genes in sporadic colorectal cancer through an interaction with folate/vitamin B_(12) status

AIM:To evaluate joint effects of Methylentetra-hydrofolate reductase(MTHFR) C677T genotypes,and serum folate/vitamin B12 concentrations on promoter methylation of tumor-associated genes among Iranian colorectal cancer patients. METHODS:We examined the associations between MTHFR C677T genotype,and promoter methylation of P16,hMLH1,and hMSH2 tumor-related genes among151 sporadic colorectal cancer patients. The promoter methylation of tumor-related genes was determined by methylation-specific PCR. Eighty six patients from whom fresh tumor samples were obtained and 81 controls were also examined for serum folate and vitamin B12 concentrations by a commercial radioimmunoassay kit. RESULTS:We found 29.1% of cases had tumors with at least one methylated gene promoter. In case-case comparison,we did not find a significant association between methylation in tumors and any single genotype. However,in comparison to controls with the CC genotype,an increased risk of tumor methylation was associated with the CT genotype(OR = 2.5;95% CI,1.1-5.6) . In case-case comparisons,folate/vitamin B12 levels were positively associated with tumor methylation. Adjusted odds ratios for tumor methylation in cases with high(above median) versus low(below median) serum folate/vitamin B12 levels were 4.9(95% CI,1.4-17.7) ,and 3.9(95% CI,1.1-13.9) ,respectively. The frequency of methylated tumors was significantly higher in high methyl donor than low methyl donor group,especially in those with MTHFR CT(P = 0.01) ,and CT/TT(P = 0.002) genotypes,but not in those with the CC genotype(P = 1.0) . CONCLUSION:We conclude that high concentrations of serum folate/vitamin B12 levels are associated with the risk of promoter methylation in tumor-specific genes,and this relationship is modified by MTHFR C677T genotypes.

Clinical characteristics,gastrointestinal manifestations and outcomes of COVID-19 patients in Iran;does the location matters?

BACKGROUND Coronavirus disease 2019(COVID-19)started in Asia,and Iran was one of its first epicenters.AIM To study the gastrointestinal(GI)symptoms and comorbidities associated with this pandemic in four different regions of Iran.METHODS We analyzed data from severe acute respiratory syndrome coronavirus 2 positive patients evaluated at four hospitals of Iran(n=91),including South(Shiraz),Southeast(Dezful),Rasht(North),and Northwest(Mashhad)between April and September 2020.Demographics,comorbidities and clinical findings including GI symptoms were collected.Statistical descriptive analysis and correlation analyses of symptoms,comorbidities,and mortality were performed.RESULTS The average age of COVID-19 patients was 51.1 years,and 56%were male.Mortality rate was 17%.Cough with 84.6%,shortness of breath with 71.4%,fever with 52.7%,and loss of appetite with 43.9%were the main symptoms.Overall cardiac disease was the most common comorbidity with an average of 28.5%followed by hypertension(28.5%)and diabetes(25.2%).The highest comorbidity in North(Rasht)was diabetes(30%)and in South(Dezful)hypertension(37%).Shiraz leads cardiac disease with 43.4%.The most reported GI symptoms included nausea,diarrhea,vomiting,and abdominal pain,with 42.8%,31.8%,26.8%,and 12%prevalence,respectively.In addition,albumin,alkaline phosphatase,aspartate aminotransferase,and alanine aminotransferase were elevated in 26.3%.CONCLUSION Our results show hypertension and diabetes as the most common comorbidities,but their distribution was different in COVID-19 patients in the four studied regions of Iran.Nausea,diarrhea,and elevated liver enzymes were the most common GI symptoms.There was also a high mortality rate that was associated with high infection rates in Iran at the beginning of the pandemic.