Genetics of Fertility Impairment and Hearing Loss

Led by Dr. Marry van den Heuvel-Eibrink of the Prinses Maxima Centrum (PMC), genetic samples were collected from pan-European cohorts and analysed through candidate gene studies and Genome Wide Association Studies (GWAS). The genetics team included Dr. Oliver Zolk at the University of Ulm and Dr. Linda Broer, Eva Clemens and Anne-Lotte van der Kooi at the Erasmus Medical Centre (EMC). Known genetic risk factors for female fertility impairment were investigated and novel genetic risk factors for fertility impairment and hearing loss were identified, and independent replication studies are being conducted in the USA and Canada. Analyses included both cohort and case-control approaches. Survivors in the genetic studies came from Germany, Switzerland, Italy, the Netherlands, France, Norway and the Czech Republic.

In the first two years of the project, the WP4 team worked to identify what survivor information they needed for the genetic studies of female fertility and hearing impairment, working with the data centre (WP1) and researchers in the fertility (WP3), hearing impairment (WP5) and quality of life (WP6) teams to identify common information and the best way to collect it. The WP4 team also worked closely with their data providers to obtain ethical approval to use survivor information for the project and to assess what number of survivors would be eligible for PanCareLIFE. In year three of the project, the WP4 team finalised the array that will be used to perform the genetic analysis and supported their data providers as they collected and sent data to the data centre. They also collected DNA samples and performed initial quality checks. In year four, the team at EMC analysed 1,421 DNA samples using state-of-the-art genetic arrays (Illumina Global Screening Array). In the final year of the project, the WP4 team combined the results of the genetic analysis with other survivor data from the data centre to examine genetic risk factors for fertility impairment and inner ear problems.

A protocol paper has already been published for the fertility study: A.L.F van der Kooi et al. ‘Genetic variation in gonadal impairment in female survivors of childhood cancer: a PanCareLIFE study protocol’ (https://doi.org/10.1186/s12885-018-4834-3).

More publications are on the way, which we’ll post to the Publications page!