BACKGROUND AND OBJECTIVES: Prostate cancer has a genetic component, and single nucleotide polymorphisms (SNPs) can contribute to the risk. We aimed to investigate the role of polymorphisms in 10 candidate genes with a key function in apoptosis. METHODS AND MATERIALS: Eight coding SNPs were chosen in ATM (Ser49Cys), BID (Ser56Cys), CASP8 (Asp302His), CASP10 (Val410Ile), LGALS3 (Pro64His), RASSF1 (Ser133Ala), TP53 (Arg72Pro), and TP53AIP1 (Ala7Val), and two non-coding SNPs were selected in BCL2 (-938C/A) and HDM2 (SNP309). A hospital-based case-control series of 510 prostate cancer patients and 490 healthy males from Northern Germany were genotyped for these polymorphisms. RESULTS: SNP rs4644 in LGALS3 showed evidence for a protective effect of the minor allele, encoding the His64 variant (OR 0.82, 95% CI 0.69;0.99, P = 0.04). Carriers were underrepresented among cases under a dominant model (OR 0.71; 95% CI 0.54;0.92; P = 0.01), and the effect appeared more pronounced in patients diagnosed before the age of 60 years (OR 0.52; 95% CI 0.31;0.85, P = 0.01). The other nine polymorphisms did not vary significantly between cases and controls, though subtle trends were noted for BCL2 (P = 0.07) and CASP10 (P = 0.08). The Asp302His variant of CASP8 tended to associate with a protective effect in the group with higher Gleason score under a dominant model (P = 0.03). Carriers of either the CASP8 or the CASP10 variants were underrepresented in the prostate cancer series (P = 0.02). CONCLUSIONS: These results provide first evidence to implicate the functional Pro64His variant of galectin-3 (LGALS3) in the genetic susceptibility towards prostate cancer. The potential role of polymorphisms in BCL2, CASP8, and CASP10 merits further investigation.
BACKGROUND AND OBJECTIVES:Prostate cancer has a genetic component, and single nucleotide polymorphisms (SNPs) can contribute to the risk. We aimed to investigate the role of polymorphisms in 10 candidate genes with a key function in apoptosis. METHODS AND MATERIALS: Eight coding SNPs were chosen in ATM (Ser49Cys), BID (Ser56Cys), CASP8 (Asp302His), CASP10 (Val410Ile), LGALS3 (Pro64His), RASSF1 (Ser133Ala), TP53 (Arg72Pro), and TP53AIP1 (Ala7Val), and two non-coding SNPs were selected in BCL2 (-938C/A) and HDM2 (SNP309). A hospital-based case-control series of 510 prostate cancerpatients and 490 healthy males from Northern Germany were genotyped for these polymorphisms. RESULTS: SNP rs4644 in LGALS3 showed evidence for a protective effect of the minor allele, encoding the His64 variant (OR 0.82, 95% CI 0.69;0.99, P = 0.04). Carriers were underrepresented among cases under a dominant model (OR 0.71; 95% CI 0.54;0.92; P = 0.01), and the effect appeared more pronounced in patients diagnosed before the age of 60 years (OR 0.52; 95% CI 0.31;0.85, P = 0.01). The other nine polymorphisms did not vary significantly between cases and controls, though subtle trends were noted for BCL2 (P = 0.07) and CASP10 (P = 0.08). The Asp302His variant of CASP8 tended to associate with a protective effect in the group with higher Gleason score under a dominant model (P = 0.03). Carriers of either the CASP8 or the CASP10 variants were underrepresented in the prostate cancer series (P = 0.02). CONCLUSIONS: These results provide first evidence to implicate the functional Pro64His variant of galectin-3 (LGALS3) in the genetic susceptibility towards prostate cancer. The potential role of polymorphisms in BCL2, CASP8, and CASP10 merits further investigation.
Authors: Judith S Knapp; Soum D Lokeshwar; Ulrich Vogel; Jörg Hennenlotter; Christian Schwentner; Mario W Kramer; Arnulf Stenzl; Axel S Merseburger Journal: World J Urol Date: 2012-08-15 Impact factor: 4.226
Authors: Manuel Luedeke; Irina Coinac; Carmen M Linnert; Natalia Bogdanova; Antje E Rinckleb; Mark Schrader; Walther Vogel; Josef Hoegel; Andreas Meyer; Thilo Dörk; Christiane Maier Journal: PLoS One Date: 2012-03-23 Impact factor: 3.240