Polymorphisms in the mTOR-PI3K-Akt pathway, energy balance-related exposures and colorectal cancer risk in the Netherlands Cohort Study
| Autor: | Simons, C.C.J.M., Schouten, L.J., Godschalk, R.W.L., Van Schooten, F.J., Stoll, M., Van Steen, K., van den Brandt, P.A., Weijenberg, M.P. |
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| Přispěvatelé: | RS: GROW - R1 - Prevention, Epidemiologie, Farmacologie en Toxicologie, RS: NUTRIM - R3 - Respiratory & Age-related Health, Biochemie, RS: FHML MaCSBio, RS: Carim - B01 Blood proteins & engineering |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Computer applications to medicine. Medical informatics
R858-859.7 SUSCEPTIBILITY Biochemistry Colorectal neoplasms DIET GENETIC-VARIANTS Genetics MTOR PATHWAY Molecular Biology BODY-SIZE QA299.6-433 Science & Technology GROWTH-FACTOR PATHWAY Research SCALE PROSPECTIVE COHORT Body size Computer Science Applications Computational Mathematics PHYSICAL-ACTIVITY Computational Theory and Mathematics Cohort studies Mathematical & Computational Biology SIGNALING PATHWAY Mechanistic target of rapamycin Polymorphisms Life Sciences & Biomedicine RESTRICTION Analysis |
| Zdroj: | BioData Mining BioData Mining, Vol 15, Iss 1, Pp 1-20 (2022) Biodata Mining, 15(1):2. BioMed Central |
| ISSN: | 1756-0381 |
| Popis: | Background The mTOR-PI3K-Akt pathway influences cell metabolism and (malignant) cell growth. We generated sex-specific polygenic risk scores capturing natural variation in 7 out of 10 top-ranked genes in this pathway. We studied the scores directly and in interaction with energy balance-related factors (body mass index (BMI), trouser/skirt size, height, physical activity, and early life energy restriction) in relation to colorectal cancer (CRC) risk in the Netherlands Cohort Study (NLCS) (n=120,852). The NLCS has a case-cohort design and 20.3 years of follow-up. Participants completed a baseline questionnaire on diet and cancer in 1986 when 55–69 years old. ~75% of the cohort returned toenail clippings used for DNA isolation and genotyping (n subcohort=3,793, n cases=3,464). To generate the scores, the dataset was split in two and risk alleles were defined and weighted based on sex-specific associations with CRC risk in the other dataset half, because there were no SNPs in the top-ranked genes associated with CRC risk in previous genome-wide association studies at a significance level p−5. Results Cox regression analyses showed positive associations between the sex-specific polygenic risk scores and colon but not rectal cancer risk in men and women, with hazard ratios for continuously modeled scores close to 1.10. There was no modifying effect observed of the scores on associations between the energy balance-related factors and CRC risk. However, BMI (in men), non-occupational physical activity (in women), and height (in men and women) were associated with the risk of CRC, in particular (proximal and distal) colon cancer, in the direction as expected in the lower tertiles of the sex-specific polygenic risk scores. Conclusions Current data suggest that the mTOR-PI3K-Akt pathway may be involved in colon cancer development. This study thereby sheds more light on colon cancer etiology through use of genetic variation in the mTOR-PI3K-Akt pathway. |
| Databáze: | OpenAIRE |
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