The Open Cancer Journal

2007, 1 : 1-8
Published online 2007 July 19. DOI: 10.2174/1874079000701010001
Publisher ID: TOCJ-1-1

Impact of Two Functional Progesterone Receptor Polymorphisms (PRP): +331G/A and PROGINS on the Cancer Risks in Familial Breast/Ovarian Cancer

Andrea Romano , Marleen Baars , Herman Martens , Rita Brandao , Yvonne Detisch , Eveline Jongen , Marinus J. Blok , Patrick Lindsey , Dagmar-C. Fischer and Encarna B. Gómez García
Department of Clinical Genetics, Maastricht University Medical Center, P.O. box 5800, 6202 AZ Maastricht, The Netherlands.

ABSTRACT

Background:

More than half of the families with breast and/or ovarian cancer (BC/OC) have no BRCA1 or BRCA2 mutation, moreover the broad lifetime risks reported within families with a BRCA1/2 mutation suggest other genes are also responsible.

Objective:

Assess the prevalence, gene-gene and phenotype-genotype associations of two functional progesterone receptor polymorphisms (PRP), PROGINS and +331G/A, in familial BC/OC.

Methods:

DNA samples from 318 randomly selected probands tested for BRCA1/2 mutations were genotyped for the PRP and CHEK2*1100delC variant.

Results:

BRCA1 was associated with BC at young age, p=0.002; +331A marginally with OC, p=0.07, and PROGINS with male BC, p=0.04. Homozygous +331A/A co-segregated with BRCA2 variants more frequently than expected by chance alone. Co-occurrence of +331A with a BRCA1BRCA2 mutation was associated with multiple BC events compared to +331A or BRCA1/BRCA2 alone, p=0.02.

Conclusion:

The PRP are risk factors for familial BC/OC, and +331A allele is a gene modifier of BRCA1 and BRCA2.