The GEOLynch cohort study has been established to investigate the influence of genetic, environmental and other factors on tumour risk in persons with Lynch syndrome.

The GEOLynch cohort study includes persons with Lynch syndrome (LS) only. Persons with LS carry an inherited mutation in one of the DNA mismatch repair genes MLH1, MSH2, MSH6 or PMS2 which increases their risk of several types of cancer, especially colorectal and endometrial cancer. Additionally, mutations in the EPCAM gene that result in epigenetic silencing of the MSH2 gene cause LS. Since 2006, persons with LS are invited to participate in the GEOLynch cohort study via the Netherlands Foundation for the Detection of Hereditary Tumours, the Radboud University Medical Center Nijmegen or the University Medical Centre Groningen. Moreover, persons with LS can participate in the study after contacting the researcher themselves. Participants are asked to complete a food frequency questionnaire and questionnaires about dietary supplement use, physical activity, weight, height and medication use. A buccal swab was asked of every participant recruited between 2006 and 2008. From 2012 on, newly recruited participants are asked to donate a blood sample instead of a buccal swab. Furthermore, participants who had been recruited between 2006 and 2008 were asked to complete the questionnaires again and to donate a blood sample too. Hence, follow-up measurements are available for a subset of participants. DNA has been subtracted from the buccal swabs to genotype SNPs of the IGF gene axis and polymorphisms of MTHFR C377T. Blood samples are biobanked to facilitate future analyses of biomarkers, nutrients, DNA etc. Clinical characteristics regarding performed colonoscopies and tumour diagnoses of all participants is gathered from medical records and a linkage to the nationwide network and registry of histo- and cytopathology in the Netherlands (PALGA Foundation ). Hazard ratios will be calculated to investigate the influence of genetic, environmental and other factor on tumour risk. Repeated measures analyses will be used if follow-up measurements are taken into account.

Inclusion Criteria:

• Persons with a known mutation in a gene that causes Lynch syndrome, i.e. with an inherited monoallelic pathogenic germline mutation in either the MLH1, MSH2, MSH6, PMS2 or EPCAM gene.
• Aged between 18 and 80 years at inclusion.

Exclusion Criteria:

• Additional carrier of another hereditary colon cancer predisposition syndrome (e.g. FAP)
• (Chronic) Inflammatory bowel disease
• Non-Dutch speaking
• Dementia or another mental condition that makes it impossible to fill out questionnaires
• Terminally ill persons

Men and women aged 18 to 80 years with Lynch syndrome who do or do not have a (previous) cancer diagnosis.