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Your search keyword '"Iles, Mark M [0000-0002-2603-6509]"' showing total 3 results
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1. Assessment of polygenic architecture and risk prediction based on common variants across fourteen cancers

Author

Montserrat Garcia-Closas, Ellen L. Goode, Mark M. Iles, Brian M. Wolpin, Stephen J. Chanock, Susan L. Slager, Li Hsu, Clare Turnbull, Ccfr, Michael Hoffmeister, Peter T. Campbell, Maria Teresa Landi, Paul D.P. Pharoah, Amber N. Hurson, Melissa L. Bondy, Roger L. Milne, Peter A. Kanetsky, Simon A. Gayther, Christopher A. Haiman, Nicola J. Camp, Mark A. Jenkins, Margaret Wrensch, Bcac, Ulrike Peters, Jill S. Barnholtz-Sloan, Richard S. Houlston, PanScan, Haoyu Zhang, Christopher I. Amos, Ben Kinnersley, GenoMEL, Florence Demenais, Rosalind A. Eeles, Katherine A. McGlynn, Practical, John K. Wiencke, Gicc, Katherine L. Nathanson, Stolzenberg-Solomon R, Brenda M. Birmann, Rayjean J. Hung, Donghui Li, David C. Whiteman, Ghislaine Scelo, Sonja I. Berndt, Alison P. Klein, Sarah V. Ward, Per Hall, D. Timothy Bishop, Tracy A. O'Mara, Kirsten B. Moysich, Corect, Laufey T. Amundadottir, Marjanka K. Schmidt, Ian Tomlinson, Ocac, Yan Zhang, Gloria M. Petersen, Ali Amin Al Olama, Puya Gharahkhani, Deborah J. Thompson, Paul Brennan, Douglas F. Easton, Celeste Leigh Pearce, InterLymph, Jacques Simard, Mark H. Greene, Zsofia Kote-Jarai, Nilanjan Chatterjee, Ecac, Marlene Danner Dalgaard, Mark P. Purdue, Beatrice Melin, Graham Casey, Rajesh Kumar, Jenny Chang-Claude, Thomas A. Sellers, Stephen B. Gruber, Beacon, James D. McKay, Tecac, Stephanie L. Schmit, Tom Grotmol, Kyriaki Michailidou, Immaculata De Vivo, Joellen M. Schildkraut, Eric J. Jacobs, Fredrik Wiklund, Amanda B. Spurdle, Nathaniel Rothman, Parichoy Pal Choudhury, Peter Kraft, Panc, Renal Cancer Gwas, Neil E. Caporaso, Joe Dennis, Matthew Law, Fredrick R. Schumacher, Harvey A. Risch, Stuart MacGregor, Andrew Berchuck, Ilcco, Oral Cancer Gwas, Zhang, Yan Dora [0000-0002-5302-3690], Hurson, Amber N. [0000-0001-7831-6660], Easton, Douglas F. [0000-0003-2444-3247], Milne, Roger L. [0000-0001-5764-7268], Simard, Jacques [0000-0001-6906-3390], Michailidou, Kyriaki [0000-0001-7065-1237], Dennis, Joe [0000-0003-4591-1214], Schmidt, Marjanka K. [0000-0002-2228-429X], Gharahkhani, Puya [0000-0002-4203-5952], Whiteman, David [0000-0003-2563-9559], Jenkins, Mark [0000-0002-8964-6160], Peters, Ulrike [0000-0001-5666-9318], Schmit, Stephanie L. [0000-0001-5931-1194], O’Mara, Tracy A. [0000-0002-5436-3232], Spurdle, Amanda B. [0000-0003-1337-7897], Thompson, Deborah J. [0000-0003-1465-5799], Tomlinson, Ian [0000-0003-3037-1470], Landi, Maria Teresa [0000-0003-4507-329X], Law, Matthew H. [0000-0002-4303-8821], Iles, Mark M. [0000-0002-2603-6509], Demenais, Florence [0000-0001-8361-0936], Kumar, Rajiv [0000-0002-6093-0395], MacGregor, Stuart [0000-0001-6731-8142], Bishop, D. Timothy [0000-0002-8752-8785], Houlston, Richard [0000-0002-5268-0242], Barnholtz-Sloan, Jill [0000-0001-6190-9304], Kinnersley, Ben [0000-0003-1783-6296], Amos, Christopher I. [0000-0002-8540-7023], Hung, Rayjean J. [0000-0002-4486-7496], Brennan, Paul [0000-0002-0518-8714], Birmann, Brenda M. [0000-0002-7550-5498], Camp, Nicola J. [0000-0002-4788-1998], Kraft, Peter [0000-0002-4472-8103], Pharoah, Paul D. P. [0000-0001-8494-732X], Gayther, Simon A. [0000-0001-7937-5443], Amundadottir, Laufey T. [0000-0003-1859-8971], Jacobs, Eric J. [0000-0002-8458-7659], Klein, Alison P. [0000-0003-2737-8399], Eeles, Rosalind A. [0000-0002-3698-6241], Schumacher, Fredrick R. [0000-0002-3073-7463], Greene, Mark H. [0000-0003-1852-9239], Kanetsky, Peter A. [0000-0002-5567-9618], Nathanson, Katherine L. [0000-0002-6740-0901], Wiklund, Fredrik [0000-0002-4623-0544], Chanock, Stephen J. [0000-0002-2324-3393], Garcia-Closas, Montserrat [0000-0003-1033-2650], Apollo - University of Cambridge Repository, Hurson, Amber N [0000-0001-7831-6660], Easton, Douglas F [0000-0003-2444-3247], Milne, Roger L [0000-0001-5764-7268], Schmidt, Marjanka K [0000-0002-2228-429X], Schmit, Stephanie L [0000-0001-5931-1194], O'Mara, Tracy A [0000-0002-5436-3232], Spurdle, Amanda B [0000-0003-1337-7897], Thompson, Deborah J [0000-0003-1465-5799], Law, Matthew H [0000-0002-4303-8821], Iles, Mark M [0000-0002-2603-6509], Bishop, D Timothy [0000-0002-8752-8785], Amos, Christopher I [0000-0002-8540-7023], Hung, Rayjean J [0000-0002-4486-7496], Birmann, Brenda M [0000-0002-7550-5498], Camp, Nicola J [0000-0002-4788-1998], Pharoah, Paul DP [0000-0001-8494-732X], Gayther, Simon A [0000-0001-7937-5443], Amundadottir, Laufey T [0000-0003-1859-8971], Jacobs, Eric J [0000-0002-8458-7659], Klein, Alison P [0000-0003-2737-8399], Eeles, Rosalind A [0000-0002-3698-6241], Schumacher, Fredrick R [0000-0002-3073-7463], Greene, Mark H [0000-0003-1852-9239], Kanetsky, Peter A [0000-0002-5567-9618], Nathanson, Katherine L [0000-0002-6740-0901], and Chanock, Stephen J [0000-0002-2324-3393]

Subjects
Male, 0301 basic medicine, Oncology, Multifactorial Inheritance, 45/43, General Physics and Astronomy, Diseases, Genome-wide association study, 0302 clinical medicine, Risk Factors, Neoplasms, 631/208/68, lcsh:Science, Cancer genetics, Multidisciplinary, 692/699, Incidence, article, 030220 oncology & carcinogenesis, Medical genetics, Female, Medical Genetics, medicine.medical_specialty, Science, Biology, Polymorphism, Single Nucleotide, Risk Assessment, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Breast cancer, SDG 3 - Good Health and Well-being, Internal medicine, medicine, Genetic predisposition, Animals, Humans, Genetic Predisposition to Disease, Lung cancer, Genetic association, Medicinsk genetik, Cancer och onkologi, Models, Genetic, 45, Cancer, General Chemistry, Heritability, medicine.disease, 030104 developmental biology, Sample size determination, Relative risk, Cancer and Oncology, lcsh:Q, Ovarian cancer, Genome-Wide Association Study
Abstract

Genome-wide association studies (GWAS) have led to the identification of hundreds of susceptibility loci across cancers, but the impact of further studies remains uncertain. Here we analyse summary-level data from GWAS of European ancestry across fourteen cancer sites to estimate the number of common susceptibility variants (polygenicity) and underlying effect-size distribution. All cancers show a high degree of polygenicity, involving at a minimum of thousands of loci. We project that sample sizes required to explain 80% of GWAS heritability vary from 60,000 cases for testicular to over 1,000,000 cases for lung cancer. The maximum relative risk achievable for subjects at the 99th risk percentile of underlying polygenic risk scores (PRS), compared to average risk, ranges from 12 for testicular to 2.5 for ovarian cancer. We show that PRS have potential for risk stratification for cancers of breast, colon and prostate, but less so for others because of modest heritability and lower incidence., In cancer many gene variants may contribute to disease etiology, but the impact of a given gene variant may have varied effect size. Here, the authors analyse summary statistics of genome-wide association studies from fourteen cancers, and show the utility of polygenic risk scores may vary depending on cancer type.

Published
2020

2. A comprehensive re-assessment of the association between vitamin D and cancer susceptibility using Mendelian randomization

Author

Ong, Jue-Sheng, Dixon-Suen, Suzanne C., Han, Xikun, An, Jiyuan, Liyanage, Upekha, Dusingize, Jean-Cluade, Schumacher, Johannes, Gockel, Ines, Böhmer, Anne, Jankowski, Janusz, Palles, Claire, O’Mara, Tracy, Spurdle, Amanda, Law, Matthew H., Iles, Mark M., Pharoah, Paul, Berchuck, Andrew, Zheng, Wei, Thrift, Aaron P., Olsen, Catherine, Neale, Rachel E., Gharahkhani, Puya, Webb, Penelope M., MacGregor, Stuart, Fitzgerald, Rebecca, Buas, Matt, Gammon, Marilie D., Corley, Douglas A., Shaheen, Nicholas J., Hardie, Laura J., Bird, Nigel C., Reid, Brian J., Chow, Wong-Ho, Risch, Harvey A., Ye, Weimin, Liu, Geoffrey, Romero, Yvonne, Bernstein, Leslie, Wu, Anna H., Whiteman, David E., Vaughan, Thomas, Agee, M., Alipanahi, B., Auton, A., Bell, R. K., Bryc, K., Elson, S. L., Fontanillas, P., Furlotte, N. A., Hinds, D. A., Huber, K. E., Kleinman, A., Litterman, N. K., McIntyre, M. H., Mountain, J. L., Noblin, E. S., Northover, C. A. M., Pitts, S. J., Sathirapongsasuti, J. Fah, Sazonova, O. V., Shelton, J. F., Shringarpure, S., Tian, C., Tung, J. Y., Vacic, V., Wilson, C. H., Ong, Jue-Sheng [0000-0002-6062-710X], Dixon-Suen, Suzanne C. [0000-0003-3714-8386], Han, Xikun [0000-0002-3823-7308], Gockel, Ines [0000-0001-7423-713X], Böhmer, Anne [0000-0002-5716-786X], O’Mara, Tracy [0000-0002-5436-3232], Spurdle, Amanda [0000-0003-1337-7897], Law, Matthew H. [0000-0002-4303-8821], Iles, Mark M. [0000-0002-2603-6509], Pharoah, Paul [0000-0001-8494-732X], Zheng, Wei [0000-0003-1226-070X], Thrift, Aaron P. [0000-0002-0084-5308], Olsen, Catherine [0000-0003-4483-1888], Gharahkhani, Puya [0000-0002-4203-5952], Webb, Penelope M. [0000-0003-0733-5930], MacGregor, Stuart [0000-0001-6731-8142], and Apollo - University of Cambridge Repository

Subjects
631/67/68, 45/43, article, 692/699/67/2195, 692/4028/67/2324
Abstract

Previous Mendelian randomization (MR) studies on 25-hydroxyvitamin D (25(OH)D) and cancer have typically adopted a handful of variants and found no relationship between 25(OH)D and cancer; however, issues of horizontal pleiotropy cannot be reliably addressed. Using a larger set of variants associated with 25(OH)D (74 SNPs, up from 6 previously), we perform a unified MR analysis to re-evaluate the relationship between 25(OH)D and ten cancers. Our findings are broadly consistent with previous MR studies indicating no relationship, apart from ovarian cancers (OR 0.89; 95% C.I: 0.82 to 0.96 per 1 SD change in 25(OH)D concentration) and basal cell carcinoma (OR 1.16; 95% C.I.: 1.04 to 1.28). However, after adjustment for pigmentation related variables in a multivariable MR framework, the BCC findings were attenuated. Here we report that lower 25(OH)D is unlikely to be a causal risk factor for most cancers, with our study providing more precise confidence intervals than previously possible.

Published
2021
Full Text
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3. A comprehensive re-assessment of the association between vitamin D and cancer susceptibility using Mendelian randomization

Author

Upekha E Liyanage, Amanda B. Spurdle, K. E. Huber, Anna H. Wu, J. Fah Sathirapongsasuti, Douglas A. Corley, C. Tian, Anne Böhmer, David A. Hinds, A. Auton, Xikun Han, Matt Buas, M. Agee, Rebecca C. Fitzgerald, Puya Gharahkhani, Yvonne Romero, S. L. Elson, Ines Gockel, Johannes Schumacher, Leslie Bernstein, Nigel C. Bird, Thomas L. Vaughan, E. S. Noblin, P. Fontanillas, Laura J. Hardie, Brian J. Reid, V. Vacic, M. H. McIntyre, Jiyuan An, Andrew Berchuck, Claire Palles, Weimin Ye, K. Bryc, S. J. Pitts, Jue-Sheng Ong, Geoffrey Liu, R. K. Bell, Rachel E. Neale, Marilie D. Gammon, J. L. Mountain, C. A. M. Northover, Catherine M. Olsen, C. H. Wilson, Janusz Jankowski, Matthew Law, A. Kleinman, Suzanne C. Dixon-Suen, J. Y. Tung, Aaron P. Thrift, Wong-Ho Chow, Paul Pharoah, Jean-Cluade Dusingize, Suyash Shringarpure, Mark M. Iles, Wei Zheng, N. A. Furlotte, Penelope M. Webb, B. Alipanahi, O. V. Sazonova, Stuart MacGregor, David Whiteman, J. F. Shelton, Harvey A. Risch, N. K. Litterman, Tracy A. O'Mara, Nicholas J. Shaheen, Ong, Jue-Sheng [0000-0002-6062-710X], Dixon-Suen, Suzanne C [0000-0003-3714-8386], Han, Xikun [0000-0002-3823-7308], Gockel, Ines [0000-0001-7423-713X], Böhmer, Anne [0000-0002-5716-786X], O'Mara, Tracy [0000-0002-5436-3232], Spurdle, Amanda [0000-0003-1337-7897], Law, Matthew H [0000-0002-4303-8821], Iles, Mark M [0000-0002-2603-6509], Pharoah, Paul [0000-0001-8494-732X], Zheng, Wei [0000-0003-1226-070X], Thrift, Aaron P [0000-0002-0084-5308], Olsen, Catherine [0000-0003-4483-1888], Gharahkhani, Puya [0000-0002-4203-5952], Webb, Penelope M [0000-0003-0733-5930], MacGregor, Stuart [0000-0001-6731-8142], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, Science, General Physics and Astronomy, Sunburn, Single-nucleotide polymorphism, General Biochemistry, Genetics and Molecular Biology, Article, Cancer prevention, 03 medical and health sciences, 0302 clinical medicine, Cancer epidemiology, Risk Factors, Internal medicine, Neoplasms, Mendelian randomization, Vitamin D and neurology, medicine, Humans, Genetic Predisposition to Disease, 030212 general & internal medicine, Risk factor, Vitamin D, Child, Cancer genetics, Multidisciplinary, business.industry, Pigmentation, Case-control study, Cancer, Mendelian Randomization Analysis, General Chemistry, medicine.disease, Confidence interval, 030104 developmental biology, Case-Control Studies, Multivariate Analysis, business
Abstract

Previous Mendelian randomization (MR) studies on 25-hydroxyvitamin D (25(OH)D) and cancer have typically adopted a handful of variants and found no relationship between 25(OH)D and cancer; however, issues of horizontal pleiotropy cannot be reliably addressed. Using a larger set of variants associated with 25(OH)D (74 SNPs, up from 6 previously), we perform a unified MR analysis to re-evaluate the relationship between 25(OH)D and ten cancers. Our findings are broadly consistent with previous MR studies indicating no relationship, apart from ovarian cancers (OR 0.89; 95% C.I: 0.82 to 0.96 per 1 SD change in 25(OH)D concentration) and basal cell carcinoma (OR 1.16; 95% C.I.: 1.04 to 1.28). However, after adjustment for pigmentation related variables in a multivariable MR framework, the BCC findings were attenuated. Here we report that lower 25(OH)D is unlikely to be a causal risk factor for most cancers, with our study providing more precise confidence intervals than previously possible., Studies of the genetic association between vitamin D and cancer risk have typically been underpowered. Here the authors analyse this using Mendelian Randomisation with more than 70 vitamin D variants obtained from the UK Biobank and large-scale data from various consortia, confirming null associations between vitamin D and most cancers.

Published
2020

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