HPC2/ELAC2 gene variants associated with incident prostate cancer.
The HPC2/ELAC2 gene on chromosome 17p11 was identified as a candidate gene for hereditary prostate cancer (HPC) susceptibility. Two HPC2 gene missense variants, Ser217Leu (Leu217) and Ala541Thr (Thr541) have been associated with incident prostate cancer cases in some studies, but not in others. We tested for possible associations between the two HPC2 gene variants and prostate cancer risk in incident prostate cancer cases (199) and healthy male controls (525) from the Calgary region. The Thr541 variant showed linkage disequilibrium with the Leu217 variant. The number of Leu217 homozygotes in the case and control groups (8.6 versus 8.5%) was not statistically different. Leu217 carrier status was associated with prostate cancer risk (cases 61.8% versus controls 50.3%) (OR 1.6, 95% CI 1.15-2.23). Additional analysis found that this association was not due to the co-existence of Thr541 variant (OR1.59, P=0.009). Logistic regression found that the relationship between the log odds of being a Thr541carrier and age depends on case/control status. Thr541 carriers had an increased risk for late-onset prostate cancer (P=0.028). Prostate intraepithelial neoplasia (PIN) was more common in the Leu217 allele carriers compared to non-carriers (42.3 versus 26.7%) (OR 2.05, 95% CI 1.10-3.83), and in the Thr541 carriers compared to non-carriers (50.0 versus 34.6%) (OR 1.89, 95% CI 0.75-4.78). In summary, the HPC2 gene variants Leu217 and Thr541 were associated with an increased risk for prostate cancer and for PIN in males undergoing radical prostatectomies in the Calgary region.
Adler
David
D
Southern Alberta Cancer Research Centre, Department of Oncology, University of Calgary, Room 300 Heritage Medical Research Building, 3330 Hospital Dr. NW, Calgary, Alberta, T2 N 4N1, Canada.
Kanji
Nimira
N
Southern Alberta Cancer Research Centre, Department of Oncology, University of Calgary, Room 300 Heritage Medical Research Building, 3330 Hospital Dr. NW, Calgary, Alberta, T2 N 4N1, Canada.
Trpkov
Kiril
K
Departments of Pathology and Laboratory Medicine, University of Calgary, Calgary, Alberta, Canada.
Fick
Gordon
G
Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada.
Hughes
Rhiannon M
RM
Southern Alberta Cancer Research Centre, Department of Oncology, University of Calgary, Room 300 Heritage Medical Research Building, 3330 Hospital Dr. NW, Calgary, Alberta, T2 N 4N1, Canada. rhughesb@ucalgary.ca.
D000367:Age Factors; D000483:Alleles; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007930:Leucine / Q000737:chemistry; D016015:Logistic Models; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics*; D011467:Prostate / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics*; D012306:Risk; D012694:Serine / Q000737:chemistry; D013912:Threonine / Q000737:chemistry
C421605:ELAC2 protein, human; D009363:Neoplasm Proteins; D013912:Threonine; D012694:Serine; D007930:Leucine