Impact of MTHFR gene C677T polymorphism on Bcl-2 gene methylation and protein expression in colorectal cancer.
OBJECTIVE
To investigate the impact of MTHFR C677T polymorphism on Bcl-2 gene promoter CpG island (CGI) methylation and Bcl-2 protein expression.


METHODS
MTHFR polymorphisms of 86 sporadic colorectal cancer (CRC) patients and 100 healthy volunteers were analyzed by PCR-based restriction fragment length polymorphism, and Bcl-2 promoter CGI methylation in 86 CRC tissues and 86 paired nonneoplastic adjacent tissues was determined by methylation-specific PCR. Bcl-2 oncoprotein expression in 70 CRC tissues and paired nonneoplastic adjacent tissues was detected by immunohistochemistry.


RESULTS
The frequency of MTHFR 677 T allele and combined variant genotypes (677CT + TT) in CRC patients was significantly higher than that in healthy controls (p = 0.023 and p = 0.035, respectively), and there is a significant association between 677TT or 677(CT + TT) genotypes and CRC (OR = 2.534, p = 0.045 and OR = 1.888, p = 0.035, respectively). The frequency of methylated Bcl-2 promoter CGI in tumor tissues was significantly lower than that in nonneoplastic adjacent tissues (p = 0.014). The frequency of methylated Bcl-2 promoter CGI in CRC tissues of the individuals with CC genotype was significantly higher than that of those with CT/TT genotypes (p = 0.018), there was significant distribution difference of C and T alleles between individuals with methylated and unmethylated Bcl-2 promoter CGI in colorectal cancer tissues (p = 0.023). Bcl-2 promoter hypomethylation was significantly correlated with Bcl-2 oncoprotein expression in colorectal cancer tissues (r = 0.558, p < 0.001).


CONCLUSIONS
Bcl-2 promoter is hypomethylated in colorectal cancer tissue, and there is a significant correlation between MTHFR 677 TT or CT/TT genotypes and CRC or Bcl-2 promoter CGI methylation/oncoprotein expression in CRC.
Experimental Center for Medical Science Research of Teaching Hospital of Jiangsu University, Shanghai People's Hospital of Putuo District, Shanghai, PR China. zhuqinghui47@hotmail.com
Qinghui
Q
Zhu
Zhonggan
Z
Jin
Ya
Y
Yuan
Qing
Q
Lu
Danhong
D
Ge
Ming
M
Zong
D045103:5,10-Methylenetetrahydrofolate Reductase (FADH2) / Q000235:genetics*; D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism*; D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism*; D019175:DNA Methylation; D005260:Female; D005787:Gene Frequency; D019254:Genes, bcl-2; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*
D019253:Proto-Oncogene Proteins c-bcl-2; D045103:5,10-Methylenetetrahydrofolate Reductase (FADH2)