Selected aspects of inherited susceptibility to prostate cancer and tumours of different site of origin

Cybulski

Description

Epidemiologic research conducted over the last two decades has led us to believe that inherited factors play an important role in the aetiology of prostate cancer, but the genes which underlie the inherited susceptibility are elusive. The most compelling associations to date are with genes involved in DNA damage repair, including BRCA2 . In Poland we have initiated a programme to identify DNA variants which confer an increased risk of prostate cancer and other cancers. Here we review our recent results. We found that germline mutations in BRCA1 , CHEK2 and NBS1 confer an increased prostate cancer risk in Polish men. We provide evidence that CHEK2 is a multi-organ cancer susceptibility gene. We show that inherited variation in RNASEL and MSR1 genes do not contribute to prostate cancer development in Poland.

Sujets

• Prostate cancer
• DNA
• BRCA1
• BRCA2
• CHEK2
• Nibrin

Informations

• Publié par: biomed
• Publié le: 01 janvier 2007
• Nombre de lectures: 4
• Langue: English

Extrait

Hereditary Cancer in Clinical Practice 2007; 5(3) pp. 164-179

Selected aspects of inherited susceptibility to prostate cancer and tumours of different site of origin

Cezary Cybulski Katedra Patologii, Pomorska Akademia Medyczna, Szczecin

Key words: prostate cancer, DNA, BRCA1, BRCA2, CHEK2, NBS1

Corresponding author: Cezary Cybulski, Katedra Patologii, Pomorska Akademia Medyczna, ul. Unii Lubelskiej 1, 71-252 Szczecin, phone: [phone], fax: [phone], e-mail: [e-mail]

Submitted: 8 August 2007 Accepted: 4 September 2007

Abstract Epidemiologic research conducted over the last two decades has led us to believe that inherited factors play an important role in the aetiology of prostate cancer, but the genes which underlie the inherited susceptibility are elusive. The most compelling associations to date are with genes involved in DNA damage repair, including BRCA2 . In Poland we have initiated a programme to identify DNA variants which confer an increased risk of prostate cancer and other cancers. Here we review our recent results. We found that germline mutations in BRCA1 , CHEK2 and NBS1 confer an increased prostate cancer risk in Polish men. We provide evidence that CHEK2 is a multi-organ cancer susceptibility gene. We show that inherited variation in RNASEL and MSR1 genes do not contribute to prostate cancer development in Poland.

Introduction two genes to prostate cancer aetiology is relatively small [13]. Common variants in the genes in these pathways Research conducted over the last two decades has led  ( CDKN1B , CDKN1A , ATMATM , XRCC1 , ERCC2 ) also us to believe that inherited factors play an important role  have been associated with an increased risk of prostate in the aetiology of cancer [1-8]. Prostate cancer is among  i cell the leading causes of morbidity and mortality in men. cancer [14-16]. The DNA  l d a a   ma a  ge c   r s uc g i n a a l  lli r n ol g e     a i n n d     the Relatively little is known about the genetic determinants of c m y a c i l n e t   e c n o a n n t c r e o   l  of  p t a h t e h  i w nt a e y g s r   it p y o y f the genome in response this disease, but epidemiologic data suggest that dominant susceptibility genes may be responsible for up to 5% of  to DNA damage and has been implicated in the all of cases [9-10]. Through linkage analysis, numerous  pathogenesis of prostate cancer and of cancers at other chromosomal loci have been identified, but no clear s b it e e e s n .    T p h e i r s f   o p r a m p e e d r     i r n e   v P i o e l w is s h     a p  r o a p n u g la e t   i o o f  n s   t w u i d t i h e  t s h   e w   h f i o c ll h o  h wi av g e prostate susceptibility gene has emerged. Three candidate  objectives:  n susceptibility genes have been positionally cloned – HPC1 , 1) to investigate the association between inherited HPC2/ELAC2 and MSR1 – but a clear role for any of these genes in hereditary prostate cancer has not been v a a n ri d a   t p i r o o n s  i t n a   t R e N c A a S n E c L e , r    r M is S k R i 1 n ,   t N h B e S P 1 ol a is n h d     p B o R p CA la 1 t genes established [11, 12]. There is evidence that rare mutations  u ion; of genes in the DNA damage signalling pathway and cell  2) to investigate the role of CHEK2 mutations in cycle control pathway ( BRCA2 , CHEK2 and NBS1 ) inherited susceptibility to prostate cancer and predispose to prostate cancer, but the contribution of these malignancies of other sites in the Polish population.

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Hereditary Cancer in Clinical Practice 2007; 5(3)