Relationship of genetic variant distributions of WW domain-containing oxidoreductase gene with uterine cervical cancer

Int J Med Sci. 2018 Jun 14;15(10):1005-1013. doi: 10.7150/ijms.25553. eCollection 2018.

Abstract

To our knowledge, no study investigates the association of genetic variant distributions of WW domain-containing oxidoreductase (WWOX) gene with development of invasive cancer, clinicopathologic variables and patient survival in uterine cervical cancer for Taiwanese women. We therefore conducted this study to explore the clinical involvements of WWOX single nucleotide polymorphisms (SNPs) in cervical cancer. One hundred and thirty-one patients with cervical invasive cancer and 93 patients with precancerous lesions as well as 316 control women were consecutively enrolled. The genotypic frequencies of WWOX genetic variants rs73569323, rs383362, rs11545028, rs3764340 and rs12918952 were determined by real-time polymerase chain reaction. The results revealed that only WWOX SNP rs3764340 was associated between patients with cervical invasive cancer and normal controls among 5 WWOX genetic variants. Cervical cancer patients with genotypes GA/AA in WWOX SNP rs12918952 were associated with parametrium invasion and pelvic lymph node metastasis. Univariate analysis found that WWOX SNPs rs73569323 and rs11545028 were associated with patient survival, whereas multivariate analysis revealed CT/TT in rs11545028 was the only genetic variant, which could predict better overall survival, among 5 WWOX SNPs in Taiwan. In conclusion, Taiwanese women with CG/GG in WWOX SNP rs3764340 are susceptible to cervical invasive cancer. Cervical cancer patients with GA/AA in rs12918952 tend to have more risk to develop parametrium invasion and pelvic lymph node metastasis. Among 5 WWOX SNPs, rs11545028 is the only genetic variant associated with patient survival, in which CT/TT could predict better overall survival in Taiwanese women.

Keywords: WW domain-containing oxidoreductase; clinicopathologic variables; genetic variants; invasive cancer of uterine cervix; overall survival.

MeSH terms

  • Adult
  • Aged
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Oxidoreductases
  • Polymorphism, Single Nucleotide*
  • Taiwan
  • Tumor Suppressor Proteins / genetics*
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology
  • WW Domain-Containing Oxidoreductase / genetics*
  • WW Domains / genetics*

Substances

  • Tumor Suppressor Proteins
  • Oxidoreductases
  • WW Domain-Containing Oxidoreductase
  • WWOX protein, human