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Your search keyword '"van der Luijt R.B."' showing total 2 results
Start Over Author "van der Luijt R.B." Topic cancer
2 results on '"van der Luijt R.B."'

1. A novel germline mutation of PTEN associated with brain tumours of multiple lineages.

Author

Staal, F.J.T., van der Luijt, R.B., Baert, M.R.M., van Drunen, J., van Bakel, H., Peters, E., de Valk, I., van Amstel, H.K.P., Taphoorn, M.J.B., Jansen, G.H., van Veelen, C.W.M., Burgering, B., and Staal, G.E.J.

Subjects
*BRAIN tumors, *TUMOR suppressor genes, *GENETIC mutation, *PROTEIN metabolism, *PROTEINS, *FRONTAL lobe, *CELL differentiation, *BIOCHEMISTRY, *DNA, *SEQUENCE analysis, *MATHEMATICAL models, *PHENOMENOLOGICAL biology, *PHOSPHATASES, *GLIOMAS, *APOPTOSIS, *CANCER, *CELL division, *INSULIN, *TRANSFERASES, *MENINGES, *MENINGIOMA, *THEORY, *DISEASE susceptibility, *AMINO acids, *MULTIPLE tumors, *GENETIC techniques, *MOLECULAR structure
Abstract

We have identified a novel germline mutation in the PTEN tumour suppressor gene. The mutation was identified in a patient with a glioma, and turned out to be a heterozygous germline mutation of PTEN (Arg234Gln), without loss of heterozygosity in tumour DNA. The biological consequences of this germline mutation were investigated by means of transfection studies of the mutant PTEN molecule compared to wild-type PTEN. In contrast to the wild-type molecule, the mutant PTEN protein is not capable of inducing apoptosis, induces increased cell proliferation and leads to high constitutive PKB/Akt activation, which cannot be increased anymore by stimulation with insulin. The reported patient, in addition to glioma, had suffered from benign meningioma in the past but did not show any clinical signs of Cowden disease or other hereditary diseases typically associated with PTEN germline mutations. The functional consequences of the mutation in transfection studies are consistent with high proliferative activity. Together, these findings suggest that the Arg234Gln missense mutation in PTEN has oncogenic properties and predisposes to brain tumours of multiple lineages. [ABSTRACT FROM AUTHOR]

Published
2002
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2. Mendelian randomization study of adiposity-related traits and risk of breast, ovarian, prostate, lung and colorectal cancer

Author

Gao, C., Patel, C. J., Michailidou, K., Peters, U., Gong, J., Schildkraut, J., Schumacher, F. R., Zheng, W., Boffetta, P., Stucker, I., Willett, W., Gruber, S., Easton, D. F., Hunter, D. J., Sellers, T. A., Haiman, C., Henderson, B. E., Hung, R. J., Amos, C., Pierce, B. L., Lindström, S., Kraft, P., Hunter, D., Henderson, B., Sellers, T., Hopper, J. L., Southey, M. C., Makalic, E., Schmidt, D. F., Fletcher, O., Peto, J., Gibson, L., Silva, I. S., Waisfisz, Q., Meijers-Heijboer, H., Adank, M., van der Luijt, R. B., Uitterlinden, A. G., Hofman, A., Meindl, A., Schmutzler, R. K., Müller-Myhsok, B., Lichtner, P., Nevanlinna, H., Muranen, T. A., Aittomäki, K., Blomqvist, C., Chang-Claude, J., Hein, R., Dahmen, N., Beckman, L., Hall, P., Czene, K., Irwanto, A., Liu, J., Turnbull, C., Rahman, N., Cramer, D., Terry, K., Sutphen, R., Narod, S., Phelan, C., Risch, H., Pharoah, P., Gayther, S., Menon, U., Wentzensen, N., Human genetics, Amsterdam Neuroscience - Complex Trait Genetics, CCA - Oncogenesis, CCA - Quality of life, and Gao, C. and Patel, C.J. and Michailidou, K. and Peters, U. and Gong, J. and Schildkraut, J. and Schumacher, F.R. and Zheng, W. and Boffetta, P. and Stucker, I. and Willett, W. and Gruber, S. and Easton, D.F. and Hunter, D.J. and Sellers, T.A. and Haiman, C. and Henderson, B.E. and Hung, R.J. and Amos, C. and Pierce, B.L. and Lindström, S. and Kraft, P. and Hunter, D. and Henderson, B. and Sellers, T. and Amos, C. and Hopper, J.L. and Southey, M.C. and Makalic, E. and Schmidt, D.F. and Fletcher, O. and Peto, J. and Gibson, L. and Silva, I.S. and Waisfisz, Q. and Meijers-Heijboer, H. and Adank, M. and van der Luijt, R.B. and Uitterlinden, A.G. and Hofman, A. and Meindl, A. and Schmutzler, R.K. and Müller-Myhsok, B. and Lichtner, P. and Nevanlinna, H. and Muranen, T.A. and Aittomäki, K. and Blomqvist, C. and Chang-Claude, J. and Hein, R. and Dahmen, N. and Beckman, L. and Hall, P. and Czene, K. and Irwanto, A. and Liu, J. and Turnbull, C. and Rahman, N. and Cramer, D. and Terry, K. and Sutphen, R. and Narod, S. and Phelan, C. and Risch, H. and Pharoah, P. and Gayther, S. and Menon, U. and Wentzensen, N.

Subjects
Male, Oncology, obesity, Epidemiology, smoking, adcy3 gene, health statu, Colorectal Neoplasm, cancer risk, genetic risk, lung tumor, Body Mass Index, genetic heterogeneity, 0302 clinical medicine, single nucleotide polymorphism, Epidemiology of cancer, Odds Ratio, tnn13k gene, 030212 general & internal medicine, sec16b gene, 2. Zero hunger, prostate tumor, breast tumor, adult, public health, allele, ovary cancer, General Medicine, prostate cancer, 3. Good health, gnpda2 gene, waist hip ratio, female, Phenotype, risk factor, priority journal, ovary tumor, 030220 oncology & carcinogenesis, child health, gnat2 gene, childhood obesity, Breast Neoplasm, cancer epidemiology, Human, single nucleotide polymorphism, Adiposity, medicine.medical_specialty, gpr61 gene, colorectal cancer, Polymorphism, Single Nucleotide, Article, olfm4 gene, Regression Analysi, 03 medical and health sciences, mc4r gene, Breast cancer, SDG 3 - Good Health and Well-being, tmem18 gene, Internal medicine, pleiotropy, Mendelian randomization, medicine, cancer, controlled study, Mendelian Randomization Analysi, Risk factor, gene, Lung cancer, Post-GWAS study, health risk, genome-wide association study, fto gene, Waist-Hip Ratio, business.industry, Ovarian Neoplasm, Waist-to-hip ratio, birth weight, Cancer, Odds ratio, medicine.disease, major clinical study, Lung Neoplasm, lung cancer, confidence interval, genetic variation, Prostatic Neoplasm, Neoplasm, genetic, business, Body mass index, body ma, colorectal tumor
Abstract

Background: Adiposity traits have been associated with risk of many cancers in observational studies, but whether these associations are causal is unclear. Mendelian randomization (MR) uses genetic predictors of risk factors as instrumental variables to eliminate reverse causation and reduce confounding bias. We performed MR analyses to assess the possible causal relationship of birthweight, childhood and adult body mass index (BMI), and waist-hip ratio (WHR) on the risks of breast, ovarian, prostate, colorectal and lung cancers. Methods: We tested the association between genetic risk scores and each trait using summary statistics from published genome-wide association studies (GWAS) and from 51 537 cancer cases and 61 600 controls in the Genetic Associations and Mechanisms in Oncology (GAME-ON) Consortium. Results: We found an inverse association between the genetic score for childhood BMI and risk of breast cancer [odds ratio (OR)=0.71 per standard deviation (s.d.) increase in childhood BMI; 95% confidence interval (CI): 0.60, 0.80; P=6.5×10-5). We also found the genetic score for adult BMI to be inversely associated with breast cancer risk (OR=0.66 per s.d. increase in BMI; 95% CI: 0.57, 0.77; P=2.5×10-7), and positively associated with ovarian cancer (OR=1.35; 95% CI: 1.05, 1.72; P=0.017), lung cancer (OR=1.27; 95% CI: 1.09, 1.49; P=2.9×10-3) and colorectal cancer (OR=1.39; 95% CI: 1.06, 1.82, P=0.016). The inverse association between genetically predicted adult BMI and breast cancer risk remained even after adjusting for directional pleiotropy via MR-Egger regression. Conclusions: Findings from this study provide additional understandings of the complex relationship between adiposity and cancer risks. Our results for breast and lung cancer are particularly interesting, given previous reports of effect heterogeneity by menopausal status and smoking status. © The Author 2016; Published by Oxford University Press on behalf of the International Epidemiological Association All rights reserved.

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