Empirical Investigation of Genomic Clusters Associated with Height and the Risk of Postmenopausal Breast and Colorectal Cancer in the Netherlands Cohort Study
| Autor: | Monika Stoll, Piet A. van den Brandt, Matty P. Weijenberg, Nadine S M Offermans, Colinda C. J. M. Simons |
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| Přispěvatelé: | Epidemiologie, RS: GROW - R1 - Prevention, Biochemie, RS: FHML MaCSBio, RS: Carim - B01 Blood proteins & engineering, RS: CAPHRI - R5 - Optimising Patient Care |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Oncology
GENETIC ANALYSES medicine.medical_specialty Epidemiology Colorectal cancer medicine.drug_class QUESTIONNAIRE colorectal cancer genetic risk score DIET Breast cancer breast cancer cohort studies Risk Factors Internal medicine shared mechanisms medicine breast neoplasms Humans Genetic risk Netherlands Framingham Risk Score Proportional hazards model business.industry SCALE PROSPECTIVE COHORT Chromosome Genomics DNA colorectal neoplasms medicine.disease Postmenopause Estrogen Female business Cohort study height |
| Zdroj: | American Journal of Epidemiology, 191(3), 413-429. Oxford University Press |
| ISSN: | 0002-9262 |
| DOI: | 10.1093/aje/kwab259 |
| Popis: | We empirically investigated genomic clusters associated with both height and postmenopausal breast cancer (BC) or colorectal cancer (CRC) (or both) in the Netherlands Cohort Study to unravel shared underlying mechanisms between height and these cancers. The Netherlands Cohort Study (1986–2006) includes 120,852 participants (case-cohort study: nsubcohort = 5,000; 20.3 years of follow-up). Variants in clusters on chromosomes 2, 4, 5, 6 (2 clusters), 10, and 20 were genotyped using toenail DNA. Cluster-specific genetic risk scores were modeled in relation to height and postmenopausal BC and CRC risk using age-adjusted linear regression and multivariable-adjusted Cox regression, respectively. Only the chromosome 10 cluster risk score was associated with all 3 phenotypes in the same sex (women); that is, it was associated with increased height (βcontinuous = 0.34, P = 0.014), increased risk of hormone-receptor–positive BC (for estrogen-receptor–positive BC, hazard ratio (HRcontinuous score) = 1.10 (95% confidence interval (CI): 1.02, 1.20); for progesterone-receptor–positive BC, HRcontinuous score = 1.15 (95% CI: 1.04, 1.26)), and increased risk of distal colon (HRcontinuous score = 1.13, 95% CI: 1.01, 1.27) and rectal (HRcontinuous score = 1.14, 95% CI: 0.99, 1.30) cancer. The chromosome 10 cluster variants were all annotated to the zinc finger MIZ-type containing 1 gene (ZMIZ1), which is involved in androgen receptor activity. This suggests that hormone-related growth mechanisms could influence both height and postmenopausal BC and CRC. |
| Databáze: | OpenAIRE |
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