Unraveling Phenotype Heterogeneity in Prostate Cancer Susceptibility in Finland Utilizing Covariate-Based Analysis

Thursday, October 11, 2012 — Poster Session III
10:00 a.m. – Noon	Natcher Conference Center, Building 45	NHGRI	GEN/GENOM-5

Authors

• C.D. Cropp
• C.L. Simpson
• T. Wahlfors
• A. George
• M.S. Jones
• U. Harper
• D. Ponciano-Jackson
• T. Tammela
• J. Schleutker
• J.E. Bailey-Wilson

Abstract

Prostate cancer is the most common male cancer in developed countries. Previously, we reported a genome-wide linkage scan in 69 Finnish Hereditary Prostate Cancer (HPC) families, which replicated the HPC9 locus on 17q21-q22 and a locus on 2q37. We used ordered subset analysis (OSA) to detect other loci linked to HPC in subsets of families to detect other loci linked to HPC incorporating age of onset as a trait-related covariate to address genetic heterogeneity. The overall mean age of onset across the families was 66.2±8.8 years while the range of individual onset ages ranged from 46-98 years. Although the highest OSA LOD score with a ΔLOD (p=0.02) was 2.876 on 15q26.2-q26.3 in a subset of 40 families ascending by age at onset, no other ΔLOD scores were significant after permutation testing. To better capture the effect of age on the linkage signal, we used LODPAL to perform a linkage analysis in affected relative pairs, while adjusting for the age of each individual family member as a single covariate. Preliminary results revealed strong evidence of linkage to HPC on chromosome 15q was (LOD=4.9, 132cM) and 8q (LOD=3.1, 157cM). Permutations are ongoing to determine empirical p-values for these LOD scores.

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