The Leu33Pro polymorphism in the gene does not modify -associated breast or ovarian cancer risks: results from a multicenter study among 15,542 and mutation carriers

Anna Jakubowska (1) , Dominik Rozkrut (2) , Antonis C. Antoniou (3) , Ute Hamann (4) , Jan Lubinski (1)

1 IHCC (International Hereditary Cancer Centre), Department of Genetics and Pathology
2 Department of Statistics and Econometrics, School of Economics and Management
3 Cancer Research UK Genetic Epidemiology Unit, Department of Public Health and Primary Care
4 Division of Molecular Genome Analysis, Molecular Genetics of Breast Cancer

Integrins containing the β subunit are key players in tumor growth and metastasis. A functional Leu33Pro polymorphism (rs5918) in the β subunit of the integrin gene () has previously been suggested to act as a modifier of ovarian cancer risk in Polish mutation carriers. To investigate the association further, we genotyped 9,998 and 5,544 mutation carriers from 34 studies from the Consortium of Investigators of Modifiers of for the Leu33Pro polymorphism. Data were analysed within a Cox-proportional hazards framework using a retrospective likelihood approach. There was marginal evidence that the polymorphism was associated with an increased risk of ovarian cancer for mutation carriers (per-allele Hazard Ratio (HR) 1.11, 95% CI 1.00-1.23, p-trend 0.05). However, when the original Polish study was excluded from the analysis, the polymorphism was no longer significantly associated with ovarian cancer risk (HR 1.07, 95% CI 0.96-1.19, p-trend 0.25). There was no evidence of an association with ovarian cancer risk for mutation carriers (HR 1.09, 95% CI 0.89-1.32). The polymorphism was not associated with breast cancer risk for either or mutation carriers. The Leu33Pro polymorphism does not modify breast or ovarian cancer risk in or mutation carriers.

Mots clés: Leu33Pro; Breast cancer; Ovarian cancer

Anna Jakubowska, Dominik Rozkrut, Antonis C. Antoniou, Ute Hamann, Jan Lubinski. The Leu33Pro polymorphism in the gene does not modify -associated breast or ovarian cancer risks: results from a multicenter study among 15,542 and mutation carriers. Breast Cancer Research and Treatment, 2009, 121 (3), pp.639-649. ⟨10.1007/s10549-009-0595-7⟩. ⟨hal-00612976⟩