{"doi":"10.18174/512910","title":"Tumour development in Lynch syndrome : genes load the gun, lifestyle pulls the trigger?","abstract":"Lynch syndrome (LS) is caused by a dominantly inherited pathogenic variant in one of the DNA mismatch repair genes. Persons with LS are predisposed to early onset cancer, mainly colorectal and endometrial cancer, and colorectal adenomas which are precursor lesions of colorectal cancer. Cancer risk estimates are variable within and between families with the same mutated gene which suggests that, similar to cancer in the general population, lifestyle-related factors may be involved in cancer development. A limited number of studies on the influence of lifestyle-related factors on cancer risk exist for persons with LS. This thesis aimed at evaluating the association between the inflammatory potential of the diet and the risk of colorectal tumours (i.e. colorectal adenomas and carcinomas), between height and the risk of both colorectal and endometrial cancer, and between body mass index (BMI) at young adulthood and the risk of cancer at all sites and cancer outside the colorectum and/or outside the endometrium for persons with LS. It was also explored whether a colorectal tumour diagnosis was associated with a change in lifestyle habits. For the research aims, data of persons with LS residing in the Netherlands and participating in the GEOLynch study has been used separately or has been  used after harmonization with data of persons with LS residing in Australia, New Zealand, Canada and the USA from the Colon Cancer Family Registry (CCFR).In chapter 2, dietary intake of 457 participants of the GEOLynch study was determined with a food frequency questionnaire (FFQ) and used to calculate the adapted dietary inflammatory index (ADII). A higher ADII score reflects a higher inflammatory potential of an individual’s diet. After a median follow-up time of 59 months, 200 (43.8%) participants developed a colorectal adenoma or carcinoma (CRT). A higher inflammatory potential of the diet was not associated with the risk of CRTs for persons with LS.Harmonized data of both the GEOLynch study and CCFR has been used to evaluate the association between height and colorectal cancer risk for men and women separately and between height and endometrial cancer risk for women in chapter 3. Self-reported height of 1155 men and 1553 women was used and cancer diagnoses were obtained from or confirmed, where possible, in medical records and/or pathology reports. After 28 279 and 37 090 person years for men and women respectively, colorectal cancer was diagnosed in 511 (44.2%) men and 436 (28.1%) women. For endometrial cancer, 1544 women were included of whom 171 (11.1%) were diagnosed with endometrial cancer after 39 227 person years. No evidence for an association was observed between height and colorectal cancer for men and women, and between height and endometrial cancer for women with LS.In chapter 4, the association between body fatness, as reflected by BMI, at young adulthood and cancer risk for persons with LS was evaluated. Harmonized data of 1044 men and 1446 women with LS from the GEOLynch and CCFR studies was used. BMI at young adulthood  was calculated with self-reported height and recalled weight at the age of 18 or 20 years. Where possible, medical records and/or pathology reports were used to  identify  cancer diagnoses. A  5 kg/m2 increment in BMI at young adulthood was associated with an increased risk of cancer  at all sites for women, but not for men. No association was observed between BMI at young adulthood and cancer outside the colon for men and women with LS, and for cancers outside both the colorectum and endometrium for women with LS.Data of the GEOLynch study was used to explore if a colorectal tumour diagnosis was associated with a change in lifestyle habits for persons with LS in chapter 5. A FFQ and a general questionnaire about lifestyle habits were completed by 324 participants at both baseline and after a median follow-up of 82.0 [interquartile range, 71.4-86.3] months. A CRT was diagnosed in 1","journal":"Socio-Environmental Systems Modeling","year":2020,"id":131096,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.956,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":531993,"name":"Jesca G.M. Brouwer","orcid":"0000-0003-4099-0371","position":0,"is_corresponding":true}],"reference_count":163,"raw_metadata":null,"created_at":"2026-07-18T23:16:00.235845Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}