Clinical Significance of Gene Mutations and Polymorphic Variants and their Association with Prostate Cancer Risk in Polish Men.

Objectives: We tested the association of germline variants in BRCA1, BRCA2, CHEK2, CDKN2A, CYP1B1, HOXB13, MLH1, NBS1, NOD2 andPALB2 genes, as well as in 8q24 region, with prostate cancer (PC) risk and estimated their impact on disease clinical course, including overall survival time in Polish men with localized PC qualified for radical treatment. Materials and Methods: DNA of 110 patients with localized prostate cancer treated with radical prostatectomy (RP), from each age group and with different stages of the disease. DNA samples of the control group consisted of 111 men, volunteers, without PC (age-matched to study group). Sanger sequencing, AS-PCR, RFLP-PCR, and multiplex-PCR were used for  variants detection.Results: The percentage of men with ≥1 germline variant was higher in PC group (52.7%) than in healthy men (37.8%) (P = .03). The presence of ≥2 variants was associated with shorter survival than the presence of one or no variant in the PC group (P = .14, trend). The HOXB13 G84E was detected in 2.9% of PC men and in no healthy men (P = .19, trend, OR = 7.21). A CHEK2 truncating mutation (1100delC or IVS2+1G>A) was detected in 2/110 (1.8%) PC patients and in no healthy men (P = .29, OR=5.14). The NBS1 I171V was detected in 2/110 (1.8%) PC patients and in no men from the control group (OR=5.14, P = .29, NS).Conclusions: We conclude that the presence of more than 2 germline variants was probably associated with shorter survival of patients with localized prostate cancer qualified for radical treatment. The HOXB13 (G84E), CHEK2 (1100delC or IVS2+1G>A) truncating variants and NBS1 (I171V) are associated with PC and hereditary form of the disease. The HOXB13 (G84E) and NOD2 (3020insC) single variants are associated with shorter and CYP1B1 (48CC, 119GG) single genotypes with longer overall survival.

Cancer control : journal of the Moffitt Cancer Center. 0000 Jan [Epub]

Marta Heise, Piotr Jarzemski, Dagmara Nowak, Aneta Bąk, Anna Junkiert-Czarnecka, Maria Pilarska-Deltow, Maciej Borysiak, Beata Pilarska, Olga Haus

Faculty of Medicine, Department of Clinical Genetics, Collegium Medicum in Bydgoszcz, 49604Nicolaus Copernicus University in Toruń, Poland., Faculty of Health Sciences, Department of Urology, Collegium Medicum in Bydgoszcz, 49604Nicolaus Copernicus University in Toruń, Jan Biziel University Hospital in Bydgoszcz, Poland.

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