Einfluss von klinischen Parametern auf die Kopplung zu Susceptibilitätsloci beim familiären Prostatakarzinom in Deutschland
Martin, Ann Christine
LicenseStandard (Fassung vom 03.05.2003)
The identification of predisposing genes for hereditary prostate cancer is hampered by the pronounced genetic heterogeneity of the disease. In order to overcome heterogeneity sample splitting techniques have been used to create more homogenous subsets of the population studied. Clinical characteristics of prostate cancer have been shown to be useful parameters for such stratifications. These traits, however, are specific to one individual and not to the whole family. In this study we stratified families for linkage analysis using a classification figure that has been determined from different clinical features of the affected relatives. The dichotomous clinical characteristics selected for stratification were tumor grade (high grade vs. low grade), stage (locally advanced vs. organ confined), aggressiveness (aggressive vs. nonaggressive using the definition of the International Consortium for Prostate Cancer Genetics) and the clinical course (PSA recurrence vs. NED (no evidence of disease)). Each affected relative received a score of 0 if the more favourable and 1 if the more unfavourable state applied. The classification figure of a family was the mean of these scores within the family and ranged from 0 to 1. Conclusion: In our study population 6 of the 24 analysed loci showed a possible association between clinical features and linkage to prostate cancer predisposition. Families with a classification figure > 0.5 for aggressive tumor showed linkage to chromosome 1q24-25 and 9q12. In the group with classification figure > 0.5 linkage was observed for locally advanced and aggressive tumor. The most prominent finding was linkage of chromosome 19q13.3 in families that had a classification figure < 0.5 for tumor stage, aggressiveness and PSA recurrence. A previous study describing chromosome 19q as an aggressiveness locus indicates that our results may be not spurious.
Subject HeadingsAggressivität [GND]
Multiple myeloma [MeSH]
Prostatic neoplasms. Genetics [MeSH]