title: Gender-specific association of methylenetetrahydrofolate reductase genotype and haplotype with the aggressiveness and prognosis of clear cell renal cell carcinoma in Japanese patients.
abstract: OBJECTIVE
  To determine if the two common polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene, C677T and A1298C, affect tumour aggressiveness or prognosis of clear cell renal cell carcinoma (CCRCC) in Japanese patients.
  
  
  METHODS
  MTHFR C677T and A1298C polymorphisms have been reported to cause decreased enzyme activity, which reduces the quantity of methyl groups available for DNA methylation and leads to mis-incorporation of uracil into DNA, resulting in single-strand DNA breaks. These effects might induce the accumulation of several genetic changes, leading to the development and progression of CCRCC. Therefore, we investigated the associations between MTHFR genotypes and haplotypes and the clinicopathological characteristics and survival rates in 240 Japanese patients with histopathologically confirmed CCRCC. MTHFR C677T and A1298C were genotyped and haplotypes were analysed using appropriate software.
  
  
  RESULTS
  The variant genotypes of MTHFR A1298C were significantly associated with some advanced characteristics of CCRCC in all patients, and these associations were stronger among men. However, among women, the variant genotypes of MTHFR C677T were associated with some advanced characteristics of CCRCC and the C677T variant genotypes or the 677T-1298A haplotype was significantly associated with decreased overall survival (P = 0.007 and P = 0.009, respectively).
  
  
  CONCLUSIONS
  To our knowledge, this is the first report on the association between MTHFR polymorphisms and CCRCC aggressiveness or prognosis. These results suggest that the MTHFR genotypes and haplotype might be useful, in a gender-specific manner, as predictive factors for the clinical course of CCRCC. Furthermore, these findings will contribute to the understanding of the mechanisms underlying CCRCC progression.
authors.affiliation: Department of Urology, Graduate School of Medicine, Yamaguchi University, Ube, Japan. shigerus@yamaguchi-u.ac.jp
authors.forename: Shigeru
authors.initials: S
authors.lastname: Sakano
authors.forename: Yuji
authors.initials: Y
authors.lastname: Hinoda
authors.forename: Naoko
authors.initials: N
authors.lastname: Okayama
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kawai
authors.forename: Hideaki
authors.initials: H
authors.lastname: Ito
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nagao
authors.forename: Takahiko
authors.initials: T
authors.lastname: Hara
authors.forename: Hideyasu
authors.initials: H
authors.lastname: Matsuyama
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007564:Japan; D007680:Kidney Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D012737:Sex Factors
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2)