title: Body size, physical activity, genetic variants in the insulin-like growth factor pathway and colorectal cancer risk.
abstract: Insulin-like growth factors (IGFs) have been associated with growth, body size, physical activity and colorectal cancer (CRC). We hypothesized that variants in IGF-related genes increase the CRC susceptibility associated with a larger body size and a lack of physical activity. We assessed this in The Netherlands Cohort Study. Participants (n = 120852) completed a baseline questionnaire on diet and cancer. ~75% returned toenail clippings. Using a case-cohort approach and 16.3 years of follow-up, toenail DNA from 3768 subcohort members and 2580 CRC cases was genotyped. We aggregated unfavorable alleles (potentially increasing CRC risk) for 18 single nucleotide polymorphisms in 8 genes into a sum score. The sum score (in tertiles) and an IGF1 19-CA repeat polymorphism (19/19, 19/non-19 and non-19/non-19 repeats) in combination with body size (mostly in tertiles) and (non-)occupational physical activity (>12, 8-12 and <8 kJ/min in the job and >90, >60-90, >30-60 and ≤30 min/day) were analyzed by Cox regression. Increasingly higher hazard ratios (HRs) for CRC were observed for a larger adult body mass index, larger trouser size and tallness in the presence of more unfavorable alleles in men. HRs (95% confidence intervals) for joint effects were 1.55 (1.06-2.25), 1.78 (1.29-2.46) and 1.48 (1.01-2.17), respectively. In women, variant repeat alleles halved CRC risk irrespective of body size and physical activity. Almost no interactions tested significant. To conclude, a larger body size was a CRC risk factor in men in the presence of an accumulation of unfavorable alleles in IGF-related genes, but interactions were generally nonsignificant.
authors.affiliation: Department of Epidemiology, GROW-School for Oncology and Developmental Biology and Department of Toxicology, NUTRIM-School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands and Department of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: C C J M
authors.initials: CC
authors.lastname: Simons
authors.affiliation: Department of Epidemiology, GROW-School for Oncology and Developmental Biology and Department of Toxicology, NUTRIM-School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands and Department of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: L J
authors.initials: LJ
authors.lastname: Schouten
authors.affiliation: Department of Toxicology, NUTRIM-School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands and.
authors.forename: R
authors.initials: R
authors.lastname: Godschalk
authors.affiliation: Department of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: van Engeland
authors.affiliation: Department of Epidemiology, GROW-School for Oncology and Developmental Biology and Department of Toxicology, NUTRIM-School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands and Department of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: P A
authors.initials: PA
authors.lastname: van den Brandt
authors.affiliation: Department of Epidemiology, GROW-School for Oncology and Developmental Biology and Department of Toxicology, NUTRIM-School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands and Department of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: F J
authors.initials: FJ
authors.lastname: van Schooten
authors.affiliation: Department of Epidemiology, GROW-School for Oncology and Developmental Biology and Department of Toxicology, NUTRIM-School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands and Department of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands mp.weijenberg@maaastrichtuniversity.nl.
authors.forename: M P
authors.initials: MP
authors.lastname: Weijenberg
mesh_terms: D000368:Aged; D015992:Body Mass Index; D049628:Body Size / Q000502:physiology*; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000235:genetics; D004032:Diet; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009043:Motor Activity / Q000502:physiology*; D009426:Netherlands; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D011795:Surveys and Questionnaires
chemical_list: C583557:IGF1 protein, human; D007334:Insulin-Like Growth Factor I