Role of hormonal genes and risk of prostate cancer: gene-gene interactions in a North Indian population.
Prostate cancer represents a heterogeneous disease with varying degrees of aggressiveness, patterns of metastasis, and response to therapy. It arises from a complex etiology that involves both exogenous (diet, environment, etc.) and endogenous (hormonal and genetic) factors. The present study was performed to explore the role of various genotypes involved in steroid metabolism and synthesis in the causation of prostate cancer. Genetic polymorphism of the ER, CYP17, SRD5A2 (TA repeats), and PSA genes were analyzed in 157 cases of prostate cancer and 340 controls [170 healthy males and 170 patients of benign prostate hyperplasia (BPH)]. Mutant genotypes of ER and CYP17 showed 2- and 3- and 3.5-fold increased risk of prostate cancer, respectively, as compared to BPH and healthy controls. Interaction of mutant (homozygous and heterozygous) alleles of CYP17 with TA (0/0) led to a twofold increased risk of prostate cancer. Risk was more than twofold with the combination of mutant alleles of ER and CYP17. The PSA gene polymorphism did not show any increased risk of prostate cancer. This indicates the role of mutant allele of ER and CYP17 in the development and progression of prostate cancer and rules out any increased risk with PSA polymorphism in the north Indian population.
Sobti
R C
RC
Department of Biotechnology, Panjab University, Chandigarh, India. rcsobti@pu.ac.in
Gupta
L
L
Singh
S K
SK
Seth
A
A
Kaur
P
P
Thakur
H
H
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics; D000368:Aged; D001483:Base Sequence; D016022:Case-Control Studies; D017931:DNA Primers; D004843:Epistasis, Genetic; D047628:Estrogen Receptor alpha / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics*; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics
D017931:DNA Primers; D047628:Estrogen Receptor alpha; D013254:Steroid 17-alpha-Hydroxylase; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; D017430:Prostate-Specific Antigen