Profiling of High-risk Prostate Cancer Families in Finland

Acta Universitatis Tamperensis, No. 1533

 

By Sanna Pakkanen
November 2010
Tampere University Press
Distributed by Coronet Books
ISBN: 9789514482243
142 pages
$77.50 Paper Original


Prostate cancer is the most common cancer among males in Finland. Familial aggregation of prostate cancer was first observed in the 1950s, though age and ethnic background are now recognised as additional risk factors. Five to ten percent of prostate cancer cases can be attributed to inherited defects. The aim of this study was to further investigate familial prostate cancer in Finland using epidemiological and molecular genetic methods.

In this thesis, I aimed to further investigate the mode of familial aggregation of prostate cancer, whether there are other cancers present in these families and how these familial cancers act as a clinical disease. I performed segregation analyses for two population-based cohorts of 557 early onset and 989 late onset familial prostate cancer cases. This analysis confirmed the existence of hereditary prostate cancer in the Finnish population under a complex model that included a major susceptibility locus with Mendelian recessive inheritance as well as a polygenic/multifactorial component.

I collected detailed clinical and histopathological data for 617 males affected by prostate cancer from 202 families in Finland. I confirmed observations suggesting that familial prostate cancers show a higher grade, a higher amount of metastases and a trend toward higher PSA levels as compared to sporadic cancers. However, there was no difference in the cancer-specific survival between the cohorts.

The incidence of other cancers was investigated among familial prostate cancer patients and their relatives to define the association of prostate cancer with a cancer syndrome or second-site cancers. I found that the incidence of non-prostate cancer is not increased in either clinically aggressive or nonaggressive familial prostate cancer cases in Finland, with the exception of stomach cancer among female relatives.

I also investigated the role of PALB2 variants in hereditary and unselected Finnish prostate cancer cases. A total of six variants in PALB2 were identified. Though none of the detected PALB2 variants were associated with prostate cancer at the population level in Finland, it is still possible that some of these variants contribute to cancer susceptibility at the individual level.

In summary, this thesis confirms previous observations of familial aggregation of prostate cancer for the Finnish population and indicates that the inheritance of this disease is best explained by a recessive mode. In addition, the clinical and histopathological characteristics of familial prostate cancer are described, and the incidence of other cancers in these families are investigated. I also determined that PALB2 variants are not associated with prostate cancer at the population level in Finland.

 

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