Are cell cycle and apoptosis genes associated with prostate cancer risk in North Indian population?

Urol Oncol. 2012 Sep;30(5):555-61. doi: 10.1016/j.urolonc.2010.05.006. Epub 2010 Sep 6.

Abstract

Objective: Prostate cancer (CaP) is a heterogeneous, multifactorial, and multifocal disease. Therefore, the search for a combination of functional polymorphisms using cell cycle and apoptotic genes as tumor markers is fundamental for a more precise and reliable diagnosis. In the present study, we investigated the diagnostic value of 3 different genes associated with CaP carcinogenesis, encoding for cell cycle (MDM2, CCND1) and apoptotic (Fas) genes that are differentially expressed in CaP.

Methods: In a hospital-based case control study of northern India, blood samples were obtained from 192 CaP patients and 224 cancer-free age matched unrelated healthy controls of similar ethnicity. They were genotyped for MDM2 G309T, CCND1 G870A, Fas A670G, and G1377A polymorphisms using polymerase chain restriction fragment length polymorphism (PCR-RFLP) method.

Results: MDM2 309GG variant was at reduced risk for developing CaP (P = 0.041; OR, 0.59). Whereas CCND1 AA genotype demonstrated increased risk (P = 0.018; OR, 1.86). The diplotype analysis of Fas G670A and G1377A (G-A) was observed to be associated with a significant increase in CaP risk (P = 0.024; OR, 1.63).

Conclusion: Findings based on current sample size our results suggested a positive association of CCND1AA genotype and diplotype analysis of Fas G670A and G1377A (G-A) to be associated with CaP risk that could influence the pathophysiology, thereby modulating the risk of CaP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alleles
  • Case-Control Studies
  • Cyclin D1 / genetics*
  • Gene Frequency
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Haplotypes
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single Nucleotide*
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / genetics*
  • Proto-Oncogene Proteins c-mdm2 / genetics*
  • Risk Factors
  • fas Receptor / genetics*

Substances

  • CCND1 protein, human
  • FAS protein, human
  • fas Receptor
  • Cyclin D1
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2
  • Prostate-Specific Antigen