HRAS T81C polymorphism modulates risk of urinary bladder cancer and predicts advanced tumors in ethnic Kashmiri population

Urol Oncol. 2013 May;31(4):487-92. doi: 10.1016/j.urolonc.2011.03.004. Epub 2011 Apr 21.

Abstract

Objective: Specific acquired HRAS mutations have been found to predominate in bladder cancer, and HRAS T81C polymorphism has been determined to contribute the risk of various cancers, including bladder cancer.

Materials and methods: We screened the exon 1and 2 of HRAS and frequently detected polymorphism at nucleotide 81T to C (exon 1). A case-control study was conducted using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to test the genotype distribution of 140 bladder cancer patients in comparison with 160 cancer-free controls from a Kashmiri population.

Results: In HRAS T81C SNP, frequencies of TT, TC, and CC genotypes among controls were 84.4%, 15.6%, and 0.0%, while in cases allele frequencies were 64.3%, 30%, and 5.7%, respectively. A significant differences was observed between the control and cases with odds ratio (OR) = 3.0 and 95% confidence interval (CI) = 1.74-5.20 (P = 0.000). Interestingly, combined TC and CC genotype abundantly presented in high grade (OR = 5.4 and 95% CI = 2.8-10.2; P < 0.00) and in advanced tumors (OR = 3.3, 95% CI = 1.71-6.30; P < 0.05). A significant association of the variant allele (TC+CC) was found with male subjects (≥50) and ever smokers (P = 0.001).

Conclusion: It is evident from our study that HRAS T81C SNP moderately increases bladder cancer risk, and rare allele is a predictive marker of advanced bladder tumors.

Publication types

  • Comparative Study

MeSH terms

  • Case-Control Studies
  • DNA, Neoplasm / genetics
  • Ethnicity / genetics*
  • Female
  • Follow-Up Studies
  • Humans
  • India / epidemiology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single Nucleotide / genetics*
  • Prognosis
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Risk Factors
  • Urinary Bladder Neoplasms / epidemiology
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / pathology*

Substances

  • DNA, Neoplasm
  • HRAS protein, human
  • Proto-Oncogene Proteins p21(ras)