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


CONCLUSIONS
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.
Mandal
Raju Kumar
RK
Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Uttar Pradesh, India.
Mittal
Rama Devi
RD
D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D019938:Cyclin D1 / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000235:genetics*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D012307:Risk Factors; D019014:fas Receptor / Q000235:genetics*
C530104:CCND1 protein, human; C491901:FAS protein, human; D019014:fas Receptor; D019938:Cyclin D1; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D017430:Prostate-Specific Antigen