PT  - JOURNAL ARTICLE
AU  - Liisa M Pelttari
AU  - Johanna Kiiski
AU  - Riikka Nurminen
AU  - Anne Kallioniemi
AU  - Johanna Schleutker
AU  - Alexandra Gylfe
AU  - Lauri A Aaltonen
AU  - Arto Leminen
AU  - Päivi Heikkilä
AU  - Carl Blomqvist
AU  - Ralf Bützow
AU  - Kristiina Aittomäki
AU  - Heli Nevanlinna
TI  - A Finnish founder mutation in <em>RAD51D</em>: analysis in breast, ovarian, prostate, and colorectal cancer
AID  - 10.1136/jmedgenet-2012-100852
DP  - 2012 Jul 01
TA  - Journal of Medical Genetics
PG  - 429--432
VI  - 49
IP  - 7
4099  - http://jmg.bmj.com/content/49/7/429.short
4100  - http://jmg.bmj.com/content/49/7/429.full
SO  - J Med Genet2012 Jul 01; 49
AB  - Background RAD51D and RAD54L are involved in homologous recombination, and rare mutations in RAD51D were recently found in breast-ovarian cancer families. This study investigated RAD51D and RAD54L for mutations in breast and ovarian cancer patients in the Finnish population.Methods The study sequenced the RAD51D and RAD54L genes in 95 breast and/or ovarian cancer families and genotyped the identified mutation in an additional 2200 breast and 553 ovarian cancer patients and 2102 population controls. To investigate the role of the mutation in other common cancers, 1094 prostate and 980 colorectal cancer patients were genotyped.Results In the screening of RAD51D, one deleterious founder mutation c.576+1G>A was identified in two breast-ovarian cancer families. No mutations were found in RAD54L. Altogether, the c.576+1G>A mutation was detected in 5/707 patients with a personal or family history of ovarian cancer (OR 9.16, 95% CI 1.07 to 78.56; p=0.024), with the highest frequency among breast-ovarian cancer families (3/105 vs 1/1287 controls, OR 37.82, 95% CI 3.90 to 366.91; p=0.0016), but no elevated frequency among breast cancer patients/families (2/2105, p=1). The mutation was not found among prostate or colorectal cancer patients.Conclusions The results of this study on familial and unselected breast, ovarian, colorectal, and prostate cancer patients suggest that RAD51D is primarily a moderate penetrance susceptibility gene for ovarian cancer, with clinical significance for the carriers.