المؤلفون: Mueller, SH, Lai, AG, Valkovskaya, M, Michailidou, K, Bolla, MK, Wang, Q, Dennis, J, Lush, M, Abu-Ful, Z, Ahearn, TU, Andrulis, IL, Anton-Culver, H, Antonenkova, NN, Arndt, V, Aronson, KJ, Augustinsson, A, Baert, T, Freeman, LEB, Beckmann, MW, Behrens, S, Benitez, J, Bermisheva, M, Blomqvist, C, Bogdanova, NV, Bojesen, SE, Bonanni, B, Brenner, H, Brucker, SY, Buys, SS, Castelao, JE, Chan, TL, Chang-Claude, J, Chanock, SJ, Choi, J-Y, Chung, WK, NBCS Collaborators, Colonna, SV, CTS Consortium, Cornelissen, S, Couch, FJ, Czene, K, Daly, MB, Devilee, P, Dörk, T, Dossus, L, Dwek, M, Eccles, DM, Ekici, AB, Eliassen, AH, Engel, C, Evans, DG, Fasching, PA, Fletcher, O, Flyger, H, Gago-Dominguez, M, Gao, Y-T, García-Closas, M, García-Sáenz, JA, Genkinger, J, Gentry-Maharaj, A, Grassmann, F, Guénel, P, Gündert, M, Haeberle, L, Hahnen, E, Haiman, CA, Håkansson, N, Hall, P, Harkness, EF, Harrington, PA, Hartikainen, JM, Hartman, M, Hein, A, Ho, W-K, Hooning, MJ, Hoppe, R, Hopper, JL, Houlston, RS, Howell, A, Hunter, DJ, Huo, D, ABCTB Investigators, Ito, H, Iwasaki, M, Jakubowska, A, Janni, W, John, EM, Jones, ME, Jung, A, Kaaks, R, Kang, D, Khusnutdinova, EK, Kim, S-W, Kitahara, CM, Koutros, S, Kraft, P, Kristensen, VN, Kubelka-Sabit, K, Kurian, AW, Kwong, A, Lacey, JV, Lambrechts, D, Le Marchand, L, Li, J, Linet, M, Lo, W-Y, Long, J, Lophatananon, A, Mannermaa, A, Manoochehri, M, Margolin, S, Matsuo, K, Mavroudis, D, Menon, U, Muir, K, Murphy, RA, Nevanlinna, H, Newman, WG, Niederacher, D, O'Brien, KM, Obi, N, Offit, K, Olopade, OI, Olshan, AF, Olsson, H, Park, SK, Patel, AV, Patel, A, Perou, CM, Peto, J, Pharoah, PDP, Plaseska-Karanfilska, D, Presneau, N, Rack, B, Radice, P, Ramachandran, D, Rashid, MU, Rennert, G, Romero, A, Ruddy, KJ, Ruebner, M, Saloustros, E, Sandler, DP, Sawyer, EJ, Schmidt, MK, Schmutzler, RK, Schneider, MO, Scott, C, Shah, M, Sharma, P, Shen, C-Y, Shu, X-O, Simard, J, Surowy, H, Tamimi, RM, Tapper, WJ, Taylor, JA, Teo, SH, Teras, LR, Toland, AE, Tollenaar, RAEM, Torres, D, Torres-Mejía, G, Troester, MA, Truong, T, Vachon, CM, Vijai, J, Weinberg, CR, Wendt, C, Winqvist, R, Wolk, A, Wu, AH, Yamaji, T, Yang, XR, Yu, J-C, Zheng, W, Ziogas, A, Ziv, E, Dunning, AM, Easton, DF, Hemingway, H, Hamann, U, Kuchenbaecker, KB

المساهمون: Fletcher, Olivia, Houlston, Richard, Jones, Michael

مصطلحات موضوعية: Breast cancer susceptibility, Diverse ancestry, Gene regulation, Genome-wide association study, Rare variants, Humans, Female, Breast Neoplasms, Genetic Predisposition to Disease, Black People, Genetic Testing, Polymorphism, Single Nucleotide, Formins

جغرافية الموضوع: England

الوصف: BACKGROUND: Low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes. METHODS: We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes' coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry. RESULTS: In European ancestry samples, 14 genes were significantly associated (q < 0.05) with BC. Of those, two genes, FMNL3 (P = 6.11 × 10-6) and AC058822.1 (P = 1.47 × 10-4), represent new associations. High FMNL3 expression has previously been linked to poor prognosis in several other cancers. Meta-analysis of samples with diverse ancestry discovered further associations including established candidate genes ESR1 and CBLB. Furthermore, literature review and database query found further support for a biologically plausible link with cancer for genes CBLB, FMNL3, FGFR2, LSP1, MAP3K1, and SRGAP2C. CONCLUSIONS: Using extended gene-based aggregation tests including coding and regulatory variation, we report identification of plausible target genes for previously identified single-marker associations with BC as well as the discovery of novel genes implicated in BC development. Including multi ancestral cohorts in this study enabled the identification of otherwise missed disease associations as ESR1 (P = 1.31 × 10-5), demonstrating the importance of diversifying study cohorts.

وصف الملف: Electronic; application/pdf

العلاقة: ARTN 7; Genome Medicine: medicine in the post-genomic era, 2023, 15 (1), pp. 7 -; https://repository.icr.ac.uk/handle/internal/5757Test

الإتاحة: https://doi.org/10.1186/s13073-022-01152-5Test
https://repository.icr.ac.uk/handle/internal/5757Test

المؤلفون: Park, HA, Neumeyer, S, Michailidou, K, Bolla, MK, Wang, Q, Dennis, J, Ahearn, TU, Andrulis, IL, Anton-Culver, H, Antonenkova, NN, Arndt, V, Aronson, KJ, Augustinsson, A, Baten, A, Beane Freeman, LE, Becher, H, Beckmann, MW, Behrens, S, Benitez, J, Bermisheva, M, Bogdanova, NV, Bojesen, SE, Brauch, H, Brenner, H, Brucker, SY, Burwinkel, B, Campa, D, Canzian, F, Castelao, JE, Chanock, SJ, Chenevix-Trench, G, Clarke, CL, NBCS Collaborators, Conroy, DM, Couch, FJ, Cox, A, Cross, SS, Czene, K, Daly, MB, Devilee, P, Dörk, T, Dos-Santos-Silva, I, Dwek, M, Eccles, DM, Eliassen, AH, Engel, C, Eriksson, M, Evans, DG, Fasching, PA, Flyger, H, Fritschi, L, García-Closas, M, García-Sáenz, JA, Gaudet, MM, Giles, GG, Glendon, G, Goldberg, MS, Goldgar, DE, González-Neira, A, Grip, M, Guénel, P, Hahnen, E, Haiman, CA, Håkansson, N, Hall, P, Hamann, U, Han, S, Harkness, EF, Hart, SN, He, W, Heemskerk-Gerritsen, BAM, Hopper, JL, Hunter, DJ, ABCTB Investigators, kConFab Investigators, Jager, A, Jakubowska, A, John, EM, Jung, A, Kaaks, R, Kapoor, PM, Keeman, R, Khusnutdinova, E, Kitahara, CM, Koppert, LB, Koutros, S, Kristensen, VN, Kurian, AW, Lacey, J, Lambrechts, D, Le Marchand, L, Lo, W-Y, Lubiński, J, Mannermaa, A, Manoochehri, M, Margolin, S, Martinez, ME, Mavroudis, D, Meindl, A, Menon, U, Milne, RL, Muranen, TA, Nevanlinna, H, Newman, WG, Nordestgaard, BG, Offit, K, Olshan, AF, Olsson, H, Park-Simon, T-W, Peterlongo, P, Peto, J, Plaseska-Karanfilska, D, Presneau, N, Radice, P, Rennert, G, Rennert, HS, Romero, A, Saloustros, E, Sawyer, EJ, Schmidt, MK, Schmutzler, RK, Schoemaker, MJ, Schwentner, L, Scott, C, Shah, M, Shu, X-O, Simard, J, Smeets, A, Southey, MC, Spinelli, JJ, Stevens, V, Swerdlow, AJ, Tamimi, RM, Tapper, WJ, Taylor, JA, Terry, MB, Tomlinson, I, Troester, MA, Truong, T, Vachon, CM, van Veen, EM, Vijai, J, Wang, S, Wendt, C, Winqvist, R, Wolk, A, Ziogas, A, Dunning, AM, Pharoah, PDP, Easton, DF, Zheng, W, Kraft, P, Chang-Claude, J

مصطلحات موضوعية: 1112 Oncology and Carcinogenesis, 1117 Public Health and Health Services, Oncology & Carcinogenesis, Breast Neoplasms, Case-Control Studies, Cigarette Smoking, Female, Genetic Pleiotropy, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotyping Techniques, Humans, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide

الوصف: BACKGROUND: Despite a modest association between tobacco smoking and breast cancer risk reported by recent epidemiological studies, it is still equivocal whether smoking is causally related to breast cancer risk. METHODS: We applied Mendelian randomisation (MR) to evaluate a potential causal effect of cigarette smoking on breast cancer risk. Both individual-level data as well as summary statistics for 164 single-nucleotide polymorphisms (SNPs) reported in genome-wide association studies of lifetime smoking index (LSI) or cigarette per day (CPD) were used to obtain MR effect estimates. Data from 108,420 invasive breast cancer cases and 87,681 controls were used for the LSI analysis and for the CPD analysis conducted among ever-smokers from 26,147 cancer cases and 26,072 controls. Sensitivity analyses were conducted to address pleiotropy. RESULTS: Genetically predicted LSI was associated with increased breast cancer risk (OR 1.18 per SD, 95% CI: 1.07-1.30, P = 0.11 × 10-2), but there was no evidence of association for genetically predicted CPD (OR 1.02, 95% CI: 0.78-1.19, P = 0.85). The sensitivity analyses yielded similar results and showed no strong evidence of pleiotropic effect. CONCLUSION: Our MR study provides supportive evidence for a potential causal association with breast cancer risk for lifetime smoking exposure but not cigarettes per day among smokers.

وصف الملف: Print-Electronic; application/pdf

العلاقة: British Journal of Cancer; British Journal of Cancer, 2021, 125, (8), pp. 1135-1145; http://hdl.handle.net/10453/154661Test

الإتاحة: http://hdl.handle.net/10453/154661Test

المؤلفون: Ahearn, TU, Zhang, H, Michailidou, K, Milne, RL, Bolla, MK, Dennis, J, Dunning, AM, Lush, M, Wang, Q, Andrulis, IL, Anton-Culver, H, Arndt, V, Aronson, KJ, Auer, PL, Augustinsson, A, Baten, A, Becher, H, Behrens, S, Benitez, J, Bermisheva, M, Blomqvist, C, Bojesen, SE, Bonanni, B, Børresen-Dale, A-L, Brauch, H, Brenner, H, Brooks-Wilson, A, Brüning, T, Burwinkel, B, Buys, SS, Canzian, F, Castelao, JE, Chang-Claude, J, Chanock, SJ, Chenevix-Trench, G, Clarke, CL, NBCS Collaborators, Collée, JM, Cox, A, Cross, SS, Czene, K, Daly, MB, Devilee, P, Dörk, T, Dwek, M, Eccles, DM, Evans, DG, Fasching, PA, Figueroa, J, Floris, G, Gago-Dominguez, M, Gapstur, SM, García-Sáenz, JA, Gaudet, MM, Giles, GG, Goldberg, MS, González-Neira, A, Alnæs, GIG, Grip, M, Guénel, P, Haiman, CA, Hall, P, Hamann, U, Harkness, EF, Heemskerk-Gerritsen, BAM, Holleczek, B, Hollestelle, A, Hooning, MJ, Hoover, RN, Hopper, JL, Howell, A, ABCTB Investigators, kConFab/AOCS Investigators, Jakimovska, M, Jakubowska, A, John, EM, Jones, ME, Jung, A, Kaaks, R, Kauppila, S, Keeman, R, Khusnutdinova, E, Kitahara, CM, Ko, Y-D, Koutros, S, Kristensen, VN, Krüger, U, Kubelka-Sabit, K, Kurian, AW, Kyriacou, K, Lambrechts, D, Lee, DG, Lindblom, A, Linet, M, Lissowska, J, Llaneza, A, Lo, W-Y, MacInnis, RJ, Mannermaa, A, Manoochehri, M, Margolin, S, Martinez, ME, McLean, C, Meindl, A, Menon, U, Nevanlinna, H, Newman, WG, Nodora, J, Offit, K, Olsson, H, Orr, N, Park-Simon, T-W, Patel, AV, Peto, J, Pita, G, Plaseska-Karanfilska, D, Prentice, R, Punie, K, Pylkäs, K, Radice, P, Rennert, G, Romero, A, Rüdiger, T, Saloustros, E, Sampson, S, Sandler, DP, Sawyer, EJ, Schmutzler, RK, Schoemaker, MJ, Schöttker, B, Sherman, ME, Shu, X-O, Smichkoska, S, Southey, MC, Spinelli, JJ, Swerdlow, AJ, Tamimi, RM, Tapper, WJ, Taylor, JA, Teras, LR, Terry, MB, Torres, D, Troester, MA, Vachon, CM, van Deurzen, CHM, van Veen, EM, Wagner, P, Weinberg, CR, Wendt, C, Wesseling, J, Winqvist, R, Wolk, A, Yang, XR, Zheng, W, Couch, FJ, Simard, J, Kraft, P, Easton, DF, Pharoah, PDP, Schmidt, MK, García-Closas, M, Chatterjee, N

المساهمون: Jones, Michael, Schoemaker, Minouk

مصطلحات موضوعية: NBCS Collaborators, ABCTB Investigators, kConFab/AOCS Investigators, Humans, Breast Neoplasms, Receptor, erbB-2, Receptors, Estrogen, Progesterone, Risk, Female, Genome-Wide Association Study, Biomarkers, Tumor

الوصف: BACKGROUND: Genome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear. METHODS: Among 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes. RESULTS: Eighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions. CONCLUSION: This report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.

وصف الملف: Electronic; ?; application/pdf

العلاقة: Breast cancer research : BCR, 2022, 24 (1), pp. 2 - ?; https://repository.icr.ac.uk/handle/internal/5044Test

الإتاحة: https://doi.org/10.1186/s13058-021-01484-xTest
https://repository.icr.ac.uk/handle/internal/5044Test

المؤلفون: Morra A., Escala-Garcia M., Beesley J., Keeman R., Canisius S., Ahearn T. U., Andrulis I. L., Anton-Culver H., Arndt V., Auer P. L., Augustinsson A., Beane Freeman L. E., Becher H., Beckmann M. W., Behrens S., Bojesen S. E., Bolla M. K., Brenner H., Bruning T., Buys S. S., Caan B., Campa D., Canzian F., Castelao J. E., Chang-Claude J., Chanock S. J., Cheng T. -Y. D., Clarke C. L., Colonna S. V., Couch F. J., Cox A., Cross S. S., Czene K., Daly M. B., Dennis J., Dork T., Dossus L., Dunning A. M., Dwek M., Eccles D. M., Ekici A. B., Eliassen A. H., Eriksson M., Evans D. G., Fasching P. A., Flyger H., Fritschi L., Gago-Dominguez M., Garcia-Saenz J. A., Giles G. G., Grip M., Guenel P., Gundert M., Hahnen E., Haiman C. A., Hakansson N., Hall P., Hamann U., Hart S. N., Hartikainen J. M., Hartmann A., He W., Hooning M. J., Hoppe R., Hopper J. L., Howell A., Hunter D. J., Jager A., Jakubowska A., Janni W., John E. M., Jung A. Y., Kaaks R., Keupers M., Kitahara C. M., Koutros S., Kraft P., Kristensen V. N., Kurian A. W., Lacey J. V., Lambrechts D., Le Marchand L., Lindblom A., Linet M., Luben R. N., Lubinski J., Lush M., Mannermaa A., Manoochehri M., Margolin S., Martens J. W. M., Martinez M. E., Mavroudis D., Michailidou K., Milne R. L., Mulligan A. M., Muranen T. A., Nevanlinna H., Newman W. G., Nielsen S. F., Nordestgaard B. G., Olshan A. F., Olsson H., Orr N., Park-Simon T. -W., Patel A. V., Peissel B., Peterlongo P., Plaseska-Karanfilska D., Prajzendanc K., Prentice R., Presneau N., Rack B., Rennert G., Rennert H. S., Rhenius V., Romero A., Roylance R., Ruebner M., Saloustros E., Sawyer E. J., Schmutzler R. K., Schneeweiss A., Scott C., Shah M., Smichkoska S., Southey M. C., Stone J., Surowy H., Swerdlow A. J., Tamimi R. M., Tapper W. J., Teras L. R., Terry M. B., Tollenaar R. A. E. M., Tomlinson I., Troester M. A., Truong T., Vachon C. M., Wang Q., Hurson A. N., Winqvist R., Wolk A., Ziogas A., Brauch H., Garcia-Closas M., Pharoah P. D. P., Easton D. F., Chenevix-Trench G., Schmidt M. K.

المساهمون: Morra, A., Escala-Garcia, M., Beesley, J., Keeman, R., Canisius, S., Ahearn, T. U., Andrulis, I. L., Anton-Culver, H., Arndt, V., Auer, P. L., Augustinsson, A., Beane Freeman, L. E., Becher, H., Beckmann, M. W., Behrens, S., Bojesen, S. E., Bolla, M. K., Brenner, H., Bruning, T., Buys, S. S., Caan, B., Campa, D., Canzian, F., Castelao, J. E., Chang-Claude, J., Chanock, S. J., Cheng, T. -Y. D., Clarke, C. L., Colonna, S. V., Couch, F. J., Cox, A., Cross, S. S., Czene, K., Daly, M. B., Dennis, J., Dork, T., Dossus, L., Dunning, A. M., Dwek, M., Eccles, D. M., Ekici, A. B., Eliassen, A. H., Eriksson, M., Evans, D. G., Fasching, P. A., Flyger, H., Fritschi, L., Gago-Dominguez, M., Garcia-Saenz, J. A., Giles, G. G., Grip, M., Guenel, P., Gundert, M., Hahnen, E., Haiman, C. A., Hakansson, N., Hall, P., Hamann, U., Hart, S. N., Hartikainen, J. M., Hartmann, A., He, W., Hooning, M. J., Hoppe, R., Hopper, J. L., Howell, A., Hunter, D. J., Jager, A., Jakubowska, A., Janni, W., John, E. M., Jung, A. Y., Kaaks, R., Keupers, M., Kitahara, C. M., Koutros, S., Kraft, P., Kristensen, V. N., Kurian, A. W., Lacey, J. V., Lambrechts, D., Le Marchand, L., Lindblom, A., Linet, M., Luben, R. N., Lubinski, J., Lush, M., Mannermaa, A., Manoochehri, M., Margolin, S., Martens, J. W. M., Martinez, M. E., Mavroudis, D., Michailidou, K., Milne, R. L., Mulligan, A. M., Muranen, T. A., Nevanlinna, H., Newman, W. G., Nielsen, S. F.

مصطلحات موضوعية: Breast cancer-specific survival, Common germline genetic variant, Patient subgroup, Systemic treatment, Tumor biology, Breast Neoplasm, Female, Genome-Wide Association Study, Human, Polymorphism, Single Nucleotide, Prognosi, Survival Analysi, Germ-Line Mutation

الوصف: BACKGROUND: Given the high heterogeneity among breast tumors, associations between common germline genetic variants and survival that may exist within specific subgroups could go undetected in an unstratified set of breast cancer patients. METHODS: We performed genome-wide association analyses within 15 subgroups of breast cancer patients based on prognostic factors, including hormone receptors, tumor grade, age, and type of systemic treatment. Analyses were based on 91,686 female patients of European ancestry from the Breast Cancer Association Consortium, including 7531 breast cancer-specific deaths over a median follow-up of 8.1 years. Cox regression was used to assess associations of common germline variants with 15-year and 5-year breast cancer-specific survival. We assessed the probability of these associations being true positives via the Bayesian false discovery probability (BFDP < 0.15). RESULTS: Evidence of associations with breast cancer-specific survival was observed in three patient subgroups, with variant rs5934618 in patients with grade 3 tumors (15-year-hazard ratio (HR) [95% confidence interval (CI)] 1.32 [1.20, 1.45], P = 1.4E-08, BFDP = 0.01, per G allele); variant rs4679741 in patients with ER-positive tumors treated with endocrine therapy (15-year-HR [95% CI] 1.18 [1.11, 1.26], P = 1.6E-07, BFDP = 0.09, per G allele); variants rs1106333 (15-year-HR [95% CI] 1.68 [1.39,2.03], P = 5.6E-08, BFDP = 0.12, per A allele) and rs78754389 (5-year-HR [95% CI] 1.79 [1.46,2.20], P = 1.7E-08, BFDP = 0.07, per A allele), in patients with ER-negative tumors treated with chemotherapy. CONCLUSIONS: We found evidence of four loci associated with breast cancer-specific survival within three patient subgroups. There was limited evidence for the existence of associations in other patient subgroups. However, the power for many subgroups is limited due to the low number of events. Even so, our results suggest that the impact of common germline genetic variants on breast cancer-specific survival might be limited.

وصف الملف: STAMPA

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/34407845; info:eu-repo/semantics/altIdentifier/wos/WOS:000687583900001; volume:23; issue:1; numberofpages:18; journal:BREAST CANCER RESEARCH; https://hdl.handle.net/11568/1133878Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85114653695; https://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-021-01450-7Test

الإتاحة: https://doi.org/10.1186/s13058-021-01450-7Test
https://hdl.handle.net/11568/1133878Test

المؤلفون: Park H. A., Neumeyer S., Michailidou K., Bolla M. K., Wang Q., Dennis J., Ahearn T. U., Andrulis I. L., Anton-Culver H., Antonenkova N. N., Arndt V., Aronson K. J., Augustinsson A., Baten A., Beane Freeman L. E., Becher H., Beckmann M. W., Behrens S., Benitez J., Bermisheva M., Bogdanova N. V., Bojesen S. E., Brauch H., Brenner H., Brucker S. Y., Burwinkel B., Campa D., Canzian F., Castelao J. E., Chanock S. J., Chenevix-Trench G., Clarke C. L., Borresen-Dale A. -L., Grenaker Alnaes G. I., Sahlberg K. K., Ottestad L., Karesen R., Schlichting E., Holmen M. M., Sauer T., Haakensen V., Engebraten O., Naume B., Fossa A., Kiserud C. E., Reinertsen K. V., Helland A., Riis M., Geisler J., Conroy D. M., Couch F. J., Cox A., Cross S. S., Czene K., Daly M. B., Devilee P., Dork T., dos-Santos-Silva I., Dwek M., Eccles D. M., Eliassen A. H., Engel C., Eriksson M., Evans D. G., Fasching P. A., Flyger H., Fritschi L., Garcia-Closas M., Garcia-Saenz J. A., Gaudet M. M., Giles G. G., Glendon G., Goldberg M. S., Goldgar D. E., Gonzalez-Neira A., Grip M., Guenel P., Hahnen E., Haiman C. A., Hakansson N., Hall P., Hamann U., Han S., Harkness E. F., Hart S. N., He W., Heemskerk-Gerritsen B. A. M., Hopper J. L., Hunter D. J., Clarke C., Marsh D., Scott R., Baxter R., Yip D., Carpenter J., Davis A., Pathmanathan N., Simpson P., Graham D., Sachchithananthan M., Amor D., Andrews L., Antill Y., Balleine R., Beesley J., Bennett I., Bogwitz M., Botes L., Brennan M., Brown M., Buckley M., Burke J., Butow P., Caldon L., Campbell I., Chauhan D., Chauhan M., Christian A., Cohen P., Colley A., Crook A., Cui J., Cummings M., Dawson S. -J., DeFazio A., Delatycki M., Dickson R., Dixon J., Edkins T., Edwards S., Farshid G., Fellows A., Fenton G., Field M., Flanagan J., Fong P., Forrest L., Fox S., French J., Friedlander M., Gaff C., Gattas M., George P., Greening S., Harris M., Hart S., Hayward N., Hopper J., Hoskins C., Hunt C., James P., Jenkins M., Kidd A., Kirk J., Koehler J., Kollias J., Lakhani S., Lawrence M., Lindeman G., Lipton L., Lobb L., Mann G., McLachlan S. A., Meiser B., Milne R., Nightingale S., O'Connell S., O'Sullivan S., Ortega D. G., Pachter N., Patterson B., Pearn A., Phillips K., Pieper E., Rickard E., Robinson B., Saleh M., Salisbury E., Saunders C., Saunus J., Scott C., Sexton A., Shelling A., Southey M., Spurdle A., Taylor J., Taylor R., Thorne H., Trainer A., Tucker K., Visvader J., Walker L., Williams R., Winship I., Young M. A., Jager A., Jakubowska A., John E. M., Jung A., Kaaks R., Kapoor P. M., Keeman R., Khusnutdinova E., Kitahara C. M., Koppert L. B., Koutros S., Kristensen V. N., Kurian A. W., Lacey J., Lambrechts D., Le Marchand L., Lo W. -Y., Lubinski J., Mannermaa A., Manoochehri M., Margolin S., Martinez M. E., Mavroudis D., Meindl A., Menon U., Milne R. L., Muranen T. A., Nevanlinna H., Newman W. G., Nordestgaard B. G., Offit K., Olshan A. F., Olsson H., Park-Simon T. -W., Peterlongo P., Peto J., Plaseska-Karanfilska D., Presneau N., Radice P., Rennert G., Rennert H. S., Romero A., Saloustros E., Sawyer E. J., Schmidt M. K., Schmutzler R. K., Schoemaker M. J., Schwentner L., Shah M., Shu X. -O., Simard J., Smeets A., Southey M. C., Spinelli J. J., Stevens V., Swerdlow A. J., Tamimi R. M., Tapper W. J., Taylor J. A., Terry M. B., Tomlinson I., Troester M. A., Truong T., Vachon C. M., van Veen E. M., Vijai J., Wang S., Wendt C., Winqvist R., Wolk A., Ziogas A., Dunning A. M., Pharoah P. D. P., Easton D. F., Zheng W., Kraft P., Chang-Claude J.

المساهمون: Park, H. A., Neumeyer, S., Michailidou, K., Bolla, M. K., Wang, Q., Dennis, J., Ahearn, T. U., Andrulis, I. L., Anton-Culver, H., Antonenkova, N. N., Arndt, V., Aronson, K. J., Augustinsson, A., Baten, A., Beane Freeman, L. E., Becher, H., Beckmann, M. W., Behrens, S., Benitez, J., Bermisheva, M., Bogdanova, N. V., Bojesen, S. E., Brauch, H., Brenner, H., Brucker, S. Y., Burwinkel, B., Campa, D., Canzian, F., Castelao, J. E., Chanock, S. J., Chenevix-Trench, G., Clarke, C. L., Borresen-Dale, A. -L., Grenaker Alnaes, G. I., Sahlberg, K. K., Ottestad, L., Karesen, R., Schlichting, E., Holmen, M. M., Sauer, T., Haakensen, V., Engebraten, O., Naume, B., Fossa, A., Kiserud, C. E., Reinertsen, K. V., Helland, A., Riis, M., Geisler, J., Conroy, D. M., Couch, F. J., Cox, A., Cross, S. S., Czene, K., Daly, M. B., Devilee, P., Dork, T., dos-Santos-Silva, I., Dwek, M., Eccles, D. M., Eliassen, A. H., Engel, C., Eriksson, M., Evans, D. G., Fasching, P. A., Flyger, H., Fritschi, L., Garcia-Closas, M., Garcia-Saenz, J. A., Gaudet, M. M., Giles, G. G., Glendon, G., Goldberg, M. S., Goldgar, D. E., Gonzalez-Neira, A., Grip, M., Guenel, P., Hahnen, E., Haiman, C. A., Hakansson, N., Hall, P., Hamann, U., Han, S., Harkness, E. F., Hart, S. N., He, W., Heemskerk-Gerritsen, B. A. M., Hopper, J. L., Hunter, D. J., Clarke, C., Marsh, D., Scott, R., Baxter, R., Yip, D., Carpenter, J., Davis, A., Pathmanathan, N., Simpson, P., Graham, D., Sachchithananthan, M.

مصطلحات موضوعية: Breast Neoplasm, Case-Control Studie, Cigarette Smoking, Female, Genetic Pleiotropy, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotyping Technique, Human, Mendelian Randomization Analysi, Polymorphism, Single Nucleotide

الوصف: Background: Despite a modest association between tobacco smoking and breast cancer risk reported by recent epidemiological studies, it is still equivocal whether smoking is causally related to breast cancer risk. Methods: We applied Mendelian randomisation (MR) to evaluate a potential causal effect of cigarette smoking on breast cancer risk. Both individual-level data as well as summary statistics for 164 single-nucleotide polymorphisms (SNPs) reported in genome-wide association studies of lifetime smoking index (LSI) or cigarette per day (CPD) were used to obtain MR effect estimates. Data from 108,420 invasive breast cancer cases and 87,681 controls were used for the LSI analysis and for the CPD analysis conducted among ever-smokers from 26,147 cancer cases and 26,072 controls. Sensitivity analyses were conducted to address pleiotropy. Results: Genetically predicted LSI was associated with increased breast cancer risk (OR 1.18 per SD, 95% CI: 1.07–1.30, P = 0.11 × 10–2), but there was no evidence of association for genetically predicted CPD (OR 1.02, 95% CI: 0.78–1.19, P = 0.85). The sensitivity analyses yielded similar results and showed no strong evidence of pleiotropic effect. Conclusion: Our MR study provides supportive evidence for a potential causal association with breast cancer risk for lifetime smoking exposure but not cigarettes per day among smokers.

وصف الملف: STAMPA

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/34341517; info:eu-repo/semantics/altIdentifier/wos/WOS:000680346000001; volume:125; issue:8; firstpage:1135; lastpage:1145; numberofpages:11; journal:BRITISH JOURNAL OF CANCER; https://hdl.handle.net/11568/1133876Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85112658433; https://www.nature.com/articles/s41416-021-01432-8Test

الإتاحة: https://doi.org/10.1038/s41416-021-01432-8Test
https://hdl.handle.net/11568/1133876Test
https://www.nature.com/articles/s41416-021-01432-8Test

المؤلفون: Johansson, M, Carreras-Torres, R, Scelo, G, Purdue, MP, Mariosa, D, Muller, DC, Timpson, NJ, Haycock, PC, Brown, KM, Wang, Z, Ye, Y, Hofmann, JN, Foll, M, Gaborieau, V, Machiela, MJ, Colli, LM, Li, P, Garnier, J-G, Blanche, H, Boland, A, Burdette, L, Prokhortchouk, E, Skryabin, KG, Yeager, M, Radojevic-Skodric, S, Ognjanovic, S, Foretova, L, Holcatova, I, Janout, V, Mates, D, Mukeriya, A, Rascu, S, Zaridze, D, Bencko, V, Cybulski, C, Fabianova, E, Jinga, V, Lissowska, J, Lubinski, J, Navratilova, M, Rudnai, P, Benhamou, S, Cancel-Tassin, G, Cussenot, O, Weiderpass, E, Ljungberg, B, Tumkur Sitaram, R, Häggström, C, Bruinsma, F, Jordan, SJ, Severi, G, Winship, I, Hveem, K, Vatten, LJ, Fletcher, T, Larsson, SC, Wolk, A, Banks, RE, Selby, PJ, Easton, DF, Andreotti, G, Beane Freeman, LE, Koutros, S, Männistö, S, Weinstein, S, Clark, PE, Edwards, TL, Lipworth, L, Gapstur, SM, Stevens, VL, Carol, H, Freedman, ML, Pomerantz, MM, Cho, E, Wilson, KM, Gaziano, JM, Sesso, HD, Freedman, ND, Parker, AS, Eckel-Passow, JE, Huang, W-Y, Kahnoski, RJ, Lane, BR, Noyes, SL, Petillo, D, Teh, BT, Peters, U, White, E, Anderson, GL, Johnson, L, Luo, J, Buring, J, Lee, I-M, Chow, W-H, Moore, LE, Eisen, T, Henrion, M, Larkin, J, Barman, P, Leibovich, BC, Choueiri, TK, Lathrop, GM, Deleuze, J-F, Gunter, M, McKay, JD, Wu, X, Houlston, RS, Chanock, SJ, Relton, C, Richards, JB, Martin, RM, Davey Smith, G, Brennan, P

المساهمون: Houlston, Richard

مصطلحات موضوعية: Humans, Carcinoma, Renal Cell, Kidney Neoplasms, Diabetes Mellitus, Type 2, Obesity, Insulin, Blood Glucose, Lipids, Genetic Markers, Body Mass Index, Risk Factors, Blood Pressure, Female, Male, Genome-Wide Association Study, Mendelian Randomization Analysis

الوصف: BACKGROUND: Several obesity-related factors have been associated with renal cell carcinoma (RCC), but it is unclear which individual factors directly influence risk. We addressed this question using genetic markers as proxies for putative risk factors and evaluated their relation to RCC risk in a mendelian randomization (MR) framework. This methodology limits bias due to confounding and is not affected by reverse causation. METHODS AND FINDINGS: Genetic markers associated with obesity measures, blood pressure, lipids, type 2 diabetes, insulin, and glucose were initially identified as instrumental variables, and their association with RCC risk was subsequently evaluated in a genome-wide association study (GWAS) of 10,784 RCC patients and 20,406 control participants in a 2-sample MR framework. The effect on RCC risk was estimated by calculating odds ratios (ORSD) for a standard deviation (SD) increment in each risk factor. The MR analysis indicated that higher body mass index increases the risk of RCC (ORSD: 1.56, 95% confidence interval [CI] 1.44-1.70), with comparable results for waist-to-hip ratio (ORSD: 1.63, 95% CI 1.40-1.90) and body fat percentage (ORSD: 1.66, 95% CI 1.44-1.90). This analysis further indicated that higher fasting insulin (ORSD: 1.82, 95% CI 1.30-2.55) and diastolic blood pressure (DBP; ORSD: 1.28, 95% CI 1.11-1.47), but not systolic blood pressure (ORSD: 0.98, 95% CI 0.84-1.14), increase the risk for RCC. No association with RCC risk was seen for lipids, overall type 2 diabetes, or fasting glucose. CONCLUSIONS: This study provides novel evidence for an etiological role of insulin in RCC, as well as confirmatory evidence that obesity and DBP influence RCC risk.

وصف الملف: Electronic-eCollection; ?; application/pdf

العلاقة: PLoS medicine, 2019, 16 (1), pp. e1002724 - ?; https://repository.icr.ac.uk/handle/internal/3728Test

الإتاحة: https://doi.org/10.1371/journal.pmed.1002724Test
https://repository.icr.ac.uk/handle/internal/3728Test

المؤلفون: Jiang X., Finucane H. K., Schumacher F. R., Schmit S. L., Tyrer J. P., Han Y., Michailidou K., Lesseur C., Kuchenbaecker K. B., Dennis J., Conti D. V., Casey G., Gaudet M. M., Huyghe J. R., Albanes D., Aldrich M. C., Andrew A. S., Andrulis I. L., Anton-Culver H., Antoniou A. C., Antonenkova N. N., Arnold S. M., Aronson K. J., Arun B. K., Bandera E. V., Barkardottir R. B., Barnes D. R., Batra J., Beckmann M. W., Benitez J., Benlloch S., Berchuck A., Berndt S. I., Bickeboller H., Bien S. A., Blomqvist C., Boccia S., Bogdanova N. V., Bojesen S. E., Bolla M. K., Brauch H., Brenner H., Brenton J. D., Brook M. N., Brunet J., Brunnstrom H., Buchanan D. D., Burwinkel B., Butzow R., Cadoni G., Caldes T., Caligo M. A., Campbell I., Campbell P. T., Cancel-Tassin G., Cannon-Albright L., Campa D., Caporaso N., Carvalho A. L., Chan A. T., Chang-Claude J., Chanock S. J., Chen C., Christiani D. C., Claes K. B. M., Claessens F., Clements J., Collee J. M., Correa M. C., Couch F. J., Cox A., Cunningham J. M., Cybulski C., Czene K., Daly M. B., deFazio A., Devilee P., Diez O., Gago-Dominguez M., Donovan J. L., Dork T., Duell E. J., Dunning A. M., Dwek M., Eccles D. M., Edlund C. K., Edwards D. R. V., Ellberg C., Evans D. G., Fasching P. A., Ferris R. L., Liloglou T., Figueiredo J. C., Fletcher O., Fortner R. T., Fostira F., Franceschi S., Friedman E., Gallinger S. J., Ganz P. A., Garber J., Garcia-Saenz J. A., Gayther S. A., Giles G. G., Godwin A. K., Goldberg M. S., Goldgar D. E., Goode E. L., Goodman M. T., Goodman G., Grankvist K., Greene M. H., Gronberg H., Gronwald J., Guenel P., Hakansson N., Hall P., Hamann U., Hamdy F. C., Hamilton R. J., Hampe J., Haugen A., Heitz F., Herrero R., Hillemanns P., Hoffmeister M., Hogdall E., Hong Y. -C., Hopper J. L., Houlston R., Hulick P. J., Hunter D. J., Huntsman D. G., Idos G., Imyanitov E. N., Ingles S. A., Isaacs C., Jakubowska A., James P., Jenkins M. A., Johansson M., John E. M., Joshi A. D., Kaneva R., Karlan B. Y., Kelemen L. E., Kuhl T., Khaw K. -T., Khusnutdinova E., Kibel A. S., Kiemeney L. A., Kim J., Kjaer S. K., Knight J. A., Kogevinas M., Kote-Jarai Z., Koutros S., Kristensen V. N., Kupryjanczyk J., Lacko M., Lam S., Lambrechts D., Landi M. T., Lazarus P., Le N. D., Lee E., Lejbkowicz F., Lenz H. -J., Leslie G., Lessel D., Lester J., Levine D. A., Li L., Li C. I., Lindblom A., Lindor N. M., Liu G., Loupakis F., Lubinski J., Maehle L., Maier C., Mannermaa A., Marchand L. L., Margolin S., May T., McGuffog L., Meindl A., Middha P., Miller A., Milne R. L., MacInnis R. J., Modugno F., Montagna M., Moreno V., Moysich K. B., Mucci L., Muir K., Mulligan A. M., Nathanson K. L., Neal D. E., Ness A. R., Neuhausen S. L., Nevanlinna H., Newcomb P. A., Newcomb L. F., Nielsen F. C., Nikitina-Zake L., Nordestgaard B. G., Nussbaum R. L., Offit K., Olah E., Olama A. A. A., Olopade O. I., Olshan A. F., Olsson H., Osorio A., Pandha H., Park J. Y., Pashayan N., Parsons M. T., Pejovic T., Penney K. L., Peters W. H. M., Phelan C. M., Phipps A. I., Plaseska-Karanfilska D., Pring M., Prokofyeva D., Radice P., Stefansson K., Ramus S. J., Raskin L., Rennert G., Rennert H. S., van Rensburg E. J., Riggan M. J., Risch H. A., Risch A., Roobol M. J., Rosenstein B. S., Rossing M. A., De Ruyck K., Saloustros E., Sandler D. P., Sawyer E. J., Schabath M. B., Schleutker J., Schmidt M. K., Setiawan V. W., Shen H., Siegel E. M., Sieh W., Singer C. F., Slattery M. L., Sorensen K. D., Southey M. C., Spurdle A. B., Stanford J. L., Stevens V. L., Stintzing S., Stone J., Sundfeldt K., Sutphen R., Swerdlow A. J., Tajara E. H., Tangen C. M., Tardon A., Taylor J. A., Teare M. D., Teixeira M. R., Terry M. B., Terry K. L., Thibodeau S. N., Thomassen M., Bjorge L., Tischkowitz M., Toland A. E., Torres D., Townsend P. A., Travis R. C., Tung N., Tworoger S. S., Ulrich C. M., Usmani N., Vachon C. M., Van Nieuwenhuysen E., Vega A., Aguado-Barrera M. E., Wang Q., Webb P. M., Weinberg C. R., Weinstein S., Weissler M. C., Weitzel J. N., West C. M. L., White E., Whittemore A. S., Wichmann H. -E., Wiklund F., Winqvist R., Wolk A., Woll P., Woods M., Wu A. H., Wu X., Yannoukakos D., Zheng W., Zienolddiny S., Ziogas A., Zorn K. K., Lane J. M., Saxena R., Thomas D., Hung R. J., Diergaarde B., McKay J., Peters U., Hsu L., Garcia-Closas M., Eeles R. A., Chenevix-Trench G., Brennan P. J., Haiman C. A., Simard J., Easton D. F., Gruber S. B., Pharoah P. D. P., Price A. L., Pasaniuc B., Amos C. I., Kraft P., Lindstrom S.

المساهمون: Jiang, X., Finucane, H. K., Schumacher, F. R., Schmit, S. L., Tyrer, J. P., Han, Y., Michailidou, K., Lesseur, C., Kuchenbaecker, K. B., Dennis, J., Conti, D. V., Casey, G., Gaudet, M. M., Huyghe, J. R., Albanes, D., Aldrich, M. C., Andrew, A. S., Andrulis, I. L., Anton-Culver, H., Antoniou, A. C., Antonenkova, N. N., Arnold, S. M., Aronson, K. J., Arun, B. K., Bandera, E. V., Barkardottir, R. B., Barnes, D. R., Batra, J., Beckmann, M. W., Benitez, J., Benlloch, S., Berchuck, A., Berndt, S. I., Bickeboller, H., Bien, S. A., Blomqvist, C., Boccia, S., Bogdanova, N. V., Bojesen, S. E., Bolla, M. K., Brauch, H., Brenner, H., Brenton, J. D., Brook, M. N., Brunet, J., Brunnstrom, H., Buchanan, D. D., Burwinkel, B., Butzow, R., Cadoni, G., Caldes, T., Caligo, M. A., Campbell, I., Campbell, P. T., Cancel-Tassin, G., Cannon-Albright, L., Campa, D., Caporaso, N., Carvalho, A. L., Chan, A. T., Chang-Claude, J., Chanock, S. J., Chen, C., Christiani, D. C., Claes, K. B. M., Claessens, F., Clements, J., Collee, J. M., Correa, M. C., Couch, F. J., Cox, A., Cunningham, J. M., Cybulski, C., Czene, K., Daly, M. B., Defazio, A., Devilee, P., Diez, O., Gago-Dominguez, M., Donovan, J. L., Dork, T., Duell, E. J., Dunning, A. M., Dwek, M., Eccles, D. M., Edlund, C. K., Edwards, D. R. V., Ellberg, C., Evans, D. G., Fasching, P. A., Ferris, R. L., Liloglou, T., Figueiredo, J. C., Fletcher, O., Fortner, R. T., Fostira, F., Franceschi, S., Friedman, E., Gallinger, S. J., Ganz, P. A.

مصطلحات موضوعية: Breast Neoplasm, Case-Control Studie, Colorectal Neoplasm, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Head and Neck Neoplasm, Human, Lung Neoplasm, Male, Mental Disorder, Neoplasm Protein, Ovarian Neoplasm, Phenotype, Polymorphism, Single Nucleotide, Prostatic Neoplasm, Smoking, Inheritance Patterns

الوصف: Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r g = 0.57, p = 4.6 × 10 −8 ), breast and ovarian cancer (r g = 0.24, p = 7 × 10 −5 ), breast and lung cancer (r g = 0.18, p=1.5 × 10 −6 ) and breast and colorectal cancer (r g = 0.15, p = 1.1 × 10 −4 ). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.

وصف الملف: STAMPA

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/30683880; info:eu-repo/semantics/altIdentifier/wos/WOS:000456696700007; volume:10; issue:1; numberofpages:23; journal:NATURE COMMUNICATIONS; https://hdl.handle.net/11568/997804Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85060528251; https://www.nature.com/articles/s41467-018-08054-4Test

الإتاحة: https://doi.org/10.1038/s41467-018-08054-4Test
https://hdl.handle.net/11568/997804Test
https://www.nature.com/articles/s41467-018-08054-4Test

المؤلفون: Law, P. J., Timofeeva, M., Fernández Rozadilla, Ceres, Broderick, P., Studd, J., Fernandez-Tajes, J., Farrington, S., Svinti, V., Palles, C., Orlando, G., Sud, A., Holroyd, A., Penegar, S., Theodoratou, E., Vaughan-Shaw, P., Campbell, H., Zgaga, L., Hayward, C., Campbell, A., Harris, S., Deary, I. J., Starr, J., Gatcombe, L., Pinna, M., Briggs, S., Martin, L., Jaeger, E., Sharma-Oates, A., East, J., Leedham, S., Arnold, R., Johnstone, E., Wang, H., Kerr, D., Kerr, R., Maughan, T., Kaplan, R., Al-Tassan, N., Palin, K., Hänninen, U. A., Cajuso, T., Tanskanen, T., Kondelin, J., Kaasinen, E., Sarin, A. P., Eriksson, J. G., Rissanen, H., Knekt, P., Pukkala, E., Jousilahti, P., Salomaa, V., Ripatti, S., Palotie, A., Renkonen-Sinisalo, L., Lepistö, A., Böhm, J., Mecklin, J. P., Buchanan, D. D., Win, A. K., Hopper, J., Jenkins, M. E., Lindor, N. M., Newcomb, P. A., Gallinger, S., Duggan, D., Casey, G., Hoffmann, P., Nöthen, M. M., Jöckel, K. H., Easton, D. F., Pharoah, P. D. P., Peto, J., Canzian, F., Swerdlow, A., Eeles, R. A., Kote-Jarai, Z., Muir, K., Pashayan, N., Henderson, B. E., Haiman, C. A., Schumacher, F. R., Al Olama, A. A., Benlloch, S., Berndt, S. I., Conti, D. V., Wiklund, F., Chanock, S., Gapstur, S., Stevens, V. L., Tangen, C. M., Batra, J., Clements, J., Gronberg, H., Schleutker, J., Albanes, D., Wolk, A., West, C., Mucci, L., Cancel-Tassin, G., Koutros, S., Sorensen, K. D., Grindedal, E. M., Neal, D. E., Hamdy, F. C., Donovan, J. L., Travis, R. C., Hamilton, R. J., Ingles, S. A., Rosenstein, B. S., Lu, Y. J., Giles, G. G., Kibel, A. S., Vega Gliemmo, Ana, Kogevinas, M., Penney, K. L., Park, J. Y., Stanford, J. L., Cybulski, C., Nordestgaard, B. G., Maier, C., Kim, J., John, E. M., Teixeira, M. R., Neuhausen, S. L., De Ruyck, K., Razack, A., Newcomb, L. F., Gamulin, M., Kaneva, R., Usmani, N., Claessens, F., Townsend, P. A., Gago-Dominguez, M., Roobol, M. J., Menegaux, F., Khaw, K. T., Cannon-Albright, L., Pandha, H., Thibodeau, S. N., Harkin, A., Allan, K., McQueen, J., Paul, J., Iveson, T., Saunders, M., Butterbach, K., Chang-Claude, J., Hoffmeister, M., Brenner, H., Kirac, I., Matošević, P., Hofer, P., Brezina, S., Gsur, A., Cheadle, J. P., Aaltonen, L. A., Tomlinson, I., Houlston, R. S., Dunlop, M. G.

المساهمون: Practical consortium

مصطلحات موضوعية: Risk Factors, European Continental Ancestry Group, Genetic Loci, Middle Aged, Inheritance Patterns, Humans, Genome-Wide Association Study, Case-Control Studies, Genetic Predisposition to Disease, Colorectal Neoplasms, Asian Continental Ancestry Group, grupo de ascendencia continental europea, estudios de casos y controles, gupo de ascendencia continental asiática, factores de riesgo, mediana edad, patrones de herencia, humanos, estudio de asociación genómica completa, sitios genéticos, predisposición genética a la enfermedad, neoplasias colorrectales, FPGMX, IDIS

الوصف: Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, and has a strong heritable basis. We report a genome-wide association analysis of 34,627 CRC cases and 71,379 controls of European ancestry that identifies SNPs at 31 new CRC risk loci. We also identify eight independent risk SNPs at the new and previously reported European CRC loci, and a further nine CRC SNPs at loci previously only identified in Asian populations. We use in situ promoter capture Hi-C (CHi-C), gene expression, and in silico annotation methods to identify likely target genes of CRC SNPs. Whilst these new SNP associations implicate target genes that are enriched for known CRC pathways such as Wnt and BMP, they also highlight novel pathways with no prior links to colorectal tumourigenesis. These findings provide further insight into CRC susceptibility and enhance the prospects of applying genetic risk scores to personalised screening and prevention.

العلاقة: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6517433/pdf/41467_2019_Article_9775.pdfTest; https://www.ncbi.nlm.nih.gov/pubmed/31089142Test; http://hdl.handle.net/20.500.11940/15791Test; 31763

الإتاحة: https://doi.org/20.500.11940/15791Test
https://doi.org/10.1038/s41467-019-09775-wTest
https://hdl.handle.net/20.500.11940/15791Test
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6517433/pdf/41467_2019_Article_9775.pdfTest
https://www.ncbi.nlm.nih.gov/pubmed/31089142Test

المؤلفون: Dadaev, T, Saunders, EJ, Newcombe, PJ, Anokian, E, Leongamornlert, DA, Brook, MN, Cieza-Borrella, C, Mijuskovic, M, Wakerell, S, Olama, AAA, Schumacher, FR, Berndt, SI, Benlloch, S, Ahmed, M, Goh, C, Sheng, X, Zhang, Z, Muir, K, Govindasami, K, Lophatananon, A, Stevens, VL, Gapstur, SM, Carter, BD, Tangen, CM, Goodman, P, Thompson, IM, Batra, J, Chambers, S, Moya, L, Clements, J, Horvath, L, Tilley, W, Risbridger, G, Gronberg, H, Aly, M, Nordström, T, Pharoah, P, Pashayan, N, Schleutker, J, Tammela, TLJ, Sipeky, C, Auvinen, A, Albanes, D, Weinstein, S, Wolk, A, Hakansson, N, West, C, Dunning, AM, Burnet, N, Mucci, L, Giovannucci, E, Andriole, G, Cussenot, O, Cancel-Tassin, G, Koutros, S, Freeman, LEB, Sorensen, KD, Orntoft, TF, Borre, M, Maehle, L, Grindedal, EM, Neal, DE, Donovan, JL, Hamdy, FC, Martin, RM, Travis, RC, Key, TJ, Hamilton, RJ, Fleshner, NE, Finelli, A, Ingles, SA, Stern, MC, Rosenstein, B, Kerns, S, Ostrer, H, Lu, Y-J, Zhang, H-W, Feng, N, Mao, X, Guo, X, Wang, G, Sun, Z, Giles, GG, Southey, MC, MacInnis, RJ, FitzGerald, LM, Kibel, AS, Drake, BF, Vega, A, Gómez-Caamaño, A, Fachal, L, Szulkin, R, Eklund, M, Kogevinas, M, Llorca, J, Castaño-Vinyals, G, Penney, KL, Stampfer, M, Park, JY, Sellers, TA, Lin, H-Y, Stanford, JL, Cybulski, C, Wokolorczyk, D, Lubinski, J, Ostrander, EA, Geybels, MS, Nordestgaard, BG, Nielsen, SF, Weisher, M, Bisbjerg, R, Røder, MA, Iversen, P, Brenner, H, Cuk, K, Holleczek, B, Maier, C, Luedeke, M, Schnoeller, T, Kim, J, Logothetis, CJ, John, EM, Teixeira, MR, Paulo, P, Cardoso, M, Neuhausen, SL, Steele, L, Ding, YC, De Ruyck, K, De Meerleer, G, Ost, P, Razack, A, Lim, J, Teo, S-H, Lin, DW, Newcomb, LF, Lessel, D, Gamulin, M, Kulis, T, Kaneva, R, Usmani, N, Slavov, C, Mitev, V, Parliament, M, Singhal, S, Claessens, F, Joniau, S, Van den Broeck, T, Larkin, S, Townsend, PA, Aukim-Hastie, C, Gago-Dominguez, M, Castelao, JE, Martinez, ME, Roobol, MJ, Jenster, G, van Schaik, RHN, Menegaux, F, Truong, T, Koudou, YA, Xu, J, Khaw, K-T, Cannon-Albright, L, Pandha, H, Michael, A, Kierzek, A, Thibodeau, SN, McDonnell, SK, Schaid, DJ, Lindstrom, S, Turman, C, Ma, J, Hunter, DJ, Riboli, E, Siddiq, A, Canzian, F, Kolonel, LN, Le Marchand, L, Hoover, RN, Machiela, MJ, Kraft, P, PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium, Freedman, M, Wiklund, F, Chanock, S, Henderson, BE, Easton, DF, Haiman, CA, Eeles, RA, Conti, DV, Kote-Jarai, Z

المساهمون: Saunders, Edward, Brook, Mark, Eeles, Rosalind, Kote-Jarai, Zsofia

مصطلحات موضوعية: PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium, Humans, Prostatic Neoplasms, Genetic Predisposition to Disease, Multivariate Analysis, Bayes Theorem, Risk, Chromosome Mapping, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Algorithms, African Continental Ancestry Group, European Continental Ancestry Group, Male, Genome-Wide Association Study, Molecular Sequence Annotation

الوصف: Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling.

وصف الملف: Electronic; ?; application/pdf

العلاقة: Nature communications, 2018, 9 (1), pp. 2256 - ?; https://repository.icr.ac.uk/handle/internal/1894Test

الإتاحة: https://doi.org/10.1038/s41467-018-04109-8Test
https://repository.icr.ac.uk/handle/internal/1894Test

المؤلفون: Scelo, G, Purdue, MP, Brown, KM, Johansson, M, Wang, Z, Eckel-Passow, JE, Ye, Y, Hofmann, JN, Choi, J, Foll, M, Gaborieau, V, Machiela, MJ, Colli, LM, Li, P, Sampson, JN, Abedi-Ardekani, B, Besse, C, Blanche, H, Boland, A, Burdette, L, Chabrier, A, Durand, G, Le Calvez-Kelm, F, Prokhortchouk, E, Robinot, N, Skryabin, KG, Wozniak, MB, Yeager, M, Basta-Jovanovic, G, Dzamic, Z, Foretova, L, Holcatova, I, Janout, V, Mates, D, Mukeriya, A, Rascu, S, Zaridze, D, Bencko, V, Cybulski, C, Fabianova, E, Jinga, V, Lissowska, J, Lubinski, J, Navratilova, M, Rudnai, P, Szeszenia-Dabrowska, N, Benhamou, S, Cancel-Tassin, G, Cussenot, O, Baglietto, L, Boeing, H, Khaw, K-T, Weiderpass, E, Ljungberg, B, Sitaram, RT, Bruinsma, F, Jordan, SJ, Severi, G, Winship, I, Hveem, K, Vatten, LJ, Fletcher, T, Koppova, K, Larsson, SC, Wolk, A, Banks, RE, Selby, PJ, Easton, DF, Pharoah, P, Andreotti, G, Freeman, LEB, Koutros, S, Albanes, D, Männistö, S, Weinstein, S, Clark, PE, Edwards, TL, Lipworth, L, Gapstur, SM, Stevens, VL, Carol, H, Freedman, ML, Pomerantz, MM, Cho, E, Kraft, P, Preston, MA, Wilson, KM, Michael Gaziano, J, Sesso, HD, Black, A, Freedman, ND, Huang, W-Y, Anema, JG, Kahnoski, RJ, Lane, BR, Noyes, SL, Petillo, D, Teh, BT, Peters, U, White, E, Anderson, GL, Johnson, L, Luo, J, Buring, J, Lee, I-M, Chow, W-H, Moore, LE, Wood, C, Eisen, T, Henrion, M, Larkin, J, Barman, P, Leibovich, BC, Choueiri, TK, Mark Lathrop, G, Rothman, N, Deleuze, J-F, McKay, JD, Parker, AS, Wu, X, Houlston, RS, Brennan, P, Chanock, SJ

المساهمون: Houlston, Richard

مصطلحات موضوعية: Humans, Carcinoma, Renal Cell, Kidney Neoplasms, Genetic Predisposition to Disease, Phenotype, Germ-Line Mutation, Polymorphism, Single Nucleotide, Adolescent, Adult, Aged, Middle Aged, European Continental Ancestry Group, Female, Male, Genome-Wide Association Study, Young Adult, Genetic Loci

الوصف: Previous genome-wide association studies (GWAS) have identified six risk loci for renal cell carcinoma (RCC). We conducted a meta-analysis of two new scans of 5,198 cases and 7,331 controls together with four existing scans, totalling 10,784 cases and 20,406 controls of European ancestry. Twenty-four loci were tested in an additional 3,182 cases and 6,301 controls. We confirm the six known RCC risk loci and identify seven new loci at 1p32.3 (rs4381241, P=3.1 × 10-10), 3p22.1 (rs67311347, P=2.5 × 10-8), 3q26.2 (rs10936602, P=8.8 × 10-9), 8p21.3 (rs2241261, P=5.8 × 10-9), 10q24.33-q25.1 (rs11813268, P=3.9 × 10-8), 11q22.3 (rs74911261, P=2.1 × 10-10) and 14q24.2 (rs4903064, P=2.2 × 10-24). Expression quantitative trait analyses suggest plausible candidate genes at these regions that may contribute to RCC susceptibility.

وصف الملف: Electronic; ?; image/png

العلاقة: Nature communications, 2017, 8 pp. 15724 - ?; https://repository.icr.ac.uk/handle/internal/1186Test

الإتاحة: https://doi.org/10.1038/ncomms15724Test
https://repository.icr.ac.uk/handle/internal/1186Test