Apoptosis gene polymorphisms and risk of prostate cancer: A hospital-based study of German patients treated with brachytherapy

Andreas Meyer, Irina Coinac, Natalia Bogdanova, Natalia Dubrowinskaja, Nurzhan Turmanov, Sabine Haubold, Peter Schürmann, Florian Imkamp, Christoph von Klot, Axel S. Merseburger, Stefan Machtens, Michael Bremer, Peter Hillemanns, Markus A. Kuczyk, Johann H. Karstens, Jürgen Serth, Thilo Dörk*

*Corresponding author for this work
15 Citations (Scopus)


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.

Original languageEnglish
JournalUrologic Oncology: Seminars and Original Investigations
Issue number1
Pages (from-to)74-81
Number of pages8
Publication statusPublished - 01.2013

Research Areas and Centers

  • Research Area: Luebeck Integrated Oncology Network (LION)


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