[Correlation between polymorphism in the promoter of DNA methyltransferase-3B and the risk of colorectal cancer].

OBJECTIVE

To explore the correlation between the polymorphism in the DNA methyltransferase-3B (DNMT3B) gene promoter single nucleotide polymorphism (SNP)-149C→T (rs2424913) and-579G→T(rs1569686) and the genetic susceptibility to colorectal cancer in Jiangsu population.

METHODS

Genomic DNA was extracted from the leukocyte cell of blood samples collected from 544 colorectal cancer (CRC) patients (including 280 cases of colon cancer and 264 cases of rectal cancer) since January 2009 and July 2010, in a hospital, Jiangsu Province. The same samples were collected from the other 533 control subjects. Polymerase chain reaction with restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing analysis were employed to assess the polymorphism of DNMT3B gene promoter-149C→T and-579G→T.

RESULTS

For DNMT3B-149C→T, no significant deviation was observed in the genotype distributions of polymorphisms between CRC cases (TT: 98.90% (538/544); CT: 1.10% (6/544)) and controls (TT: 97.75% (521/533); CT: 2.25% (12/533)) (χ(2) = 2.07, P = 0.15). The CC genotype was not detected in either patients or control subjects. The DNMT3B-149CT genotype was not associated with the risk of CRC (adjusted OR = 0.48, 95%CI: 0.18 - 1.30). For DNMT3B-579G→T, the genotype distributions of polymorphisms in CRC patients (TT: 90.07% (490/544); GT: 9.19% (50/544); GG: 0.74% (4/544)) were significantly different from those in control group (TT: 81.80% (436/533); GT: 17.82% (95/533); GG: 0.38% (2/533)) (χ(2) = 15.49, P < 0.05). The results showed that the-579 G allele could significantly decrease the risk of CRC (adjusted OR = 0.50, 95%CI: 0.35 - 0.72) in comparison with the -579 TT genotype. In addition, stratification analysis showed that for DNMT3B-579G→T, the genotype distributions of polymorphisms in colon cancer (TT: 92.50% (259/280); GT: 7.50% (21/280)) were significantly different from those in the controls (TT: 81.80% (436/533); GT: 17.82% (95/533); GG: 0.38% (2/533)) (χ(2) = 13.53, P < 0.05); and similar result was found in rectal cancer (TT: 87.50% (231/264); GT: 10.98% (29/264); GG: 1.52% (4/264)) and controls (TT: 81.80% (436/533); GT: 17.82% (95/533); GG: 0.38% (2/533)) (χ(2) = 5.64, P = 0.018). G allele carriers could decrease the risk of colon cancer (adjusted OR = 0.38, 95%CI: 0.23 - 0.63), and the risk of rectal cancer (adjusted OR = 0.65, 95%CI: 0.42 - 0.99). However, for DNMT3B-149C→T , there were no significant deviation in the genotype distributions of polymorphisms between colon cancer (TT: 98.57% (276/280); CT: 1.43% (4/280)) and controls (TT: 97.75% (521/533); CT: 2.25% (12/533)) (χ(2) = 0.82, P = 0.366); and there was no significant deviation between rectal cancer (TT: 99.24% (262/264); CT: 0.76% (2/264)) and controls (TT: 97.75% (521/533); CT: 2.25% (12/533)) either (χ(2) = 1.89, P = 0.169).

CONCLUSION

Our research demonstrates that the-579 G allele is a potential protective factor for the occurrence of CRC, however, the polymorphism of DNMT3B-149 gene shows no close correlation with the occurrence and development of CRC among Chinese population.