المؤلفون: Kote-Jarai, Z, Saunders, E, Leongamornlert, D, Tymrakiewicz, M, Dadaev, T, Jugurnauth-Little, S, Ross-Adams, H, Al Olama, A, Benlloch, S, Halim, S, Russell, R, Russel, R, Dunning, A, Luccarini, C, Dennis, J, Neal, D, Hamdy, F, Donovan, J, Muir, K, Giles, G, Severi, G, Wiklund, F, Gronberg, H, Haiman, C, Schumacher, F, Henderson, B, Le Marchand, L, Lindstrom, S, Kraft, P, Hunter, D, Gapstur, S, Chanock, S, Berndt, S, Albanes, D, Andriole, G, Schleutker, J, Weischer, M, Canzian, F, Riboli, E, Key, T, Travis, R, Campa, D, Ingles, SA, John, E, Hayes, R, Pharoah, P, Khaw, K, Stanford, J, Ostrander, E, Signorello, L, Thibodeau, SN, Schaid, D, Maier, C, Vogel, W, Kibel, A, Cybulski, C, Lubinski, J, Cannon-Albright, L, Brenner, H, Park, J, Kaneva, R, Batra, J, Spurdle, A, Clements, J, Teixeira, MR, Govindasami, K, Guy, M, Wilkinson, R, Sawyer, E, Morgan, A, Dicks, E, Baynes, C, Conroy, D, Bojesen, SE, Kaaks, R, Vincent, D, Bacot, F, Tessier, D, Easton, D, Eeles, R

الوصف: Associations between single nucleotide polymorphisms (SNPs) at 5p15 and multiple cancer types have been reported. We have previously shown evidence for a strong association between prostate cancer (PrCa) risk and rs2242652 at 5p15, intronic in the telomerase reverse transcriptase (TERT) gene that encodes TERT. To comprehensively evaluate the association between genetic variation across this region and PrCa, we performed a fine-mapping analysis by genotyping 134 SNPs using a custom Illumina iSelect array or Sequenom MassArray iPlex, followed by imputation of 1094 SNPs in 22 301 PrCa cases and 22 320 controls in The PRACTICAL consortium. Multiple stepwise logistic regression analysis identified four signals in the promoter or intronic regions of TERT that independently associated with PrCa risk. Gene expression analysis of normal prostate tissue showed evidence that SNPs within one of these regions also associated with TERT expression, providing a potential mechanism for predisposition to disease.

العلاقة: https://ora.ox.ac.uk/objects/uuid:846da098-ffb8-4c5b-8680-7dfa8b338707Test; https://doi.org/10.1093/hmg/ddt086Test

الإتاحة: https://doi.org/10.1093/hmg/ddt086Test
https://ora.ox.ac.uk/objects/uuid:846da098-ffb8-4c5b-8680-7dfa8b338707Test

المؤلفون: Mavaddat, N, Pharoah, P D P, Michailidou, K, Tyrer, J, Brook, M N, Bolla, M K, Wang, Q, Dennis, J, Dunning, A M, Shah, M, Luben, R, Brown, J, Bojesen, S E, Nordestgaard, B G, Nielsen, S F, Flyger, H, Czene, K, Darabi, H, Eriksson, M, Peto, J, Dos-Santos-Silva, I, Dudbridge, F, Johnson, N, Schmidt, M K, Broeks, A, Verhoef, S, Rutgers, E J, Swerdlow, A, Ashworth, A, Orr, N, Schoemaker, M J, Figueroa, J, Chanock, S J, Brinton, L, Lissowska, J, Couch, F J, Olson, J E, Vachon, C, Pankratz, V S, Lambrechts, D, Wildiers, H, Van Ongeval, C, Van Limbergen, E, Kristensen, V, Grenaker Alnæs, G, Nord, S, Borresen-Dale, A-L, Nevanlinna, H, Muranen, TA, Aittomäki, K, Blomqvist, C, Chang-Claude, J, Rudolph, A, Seibold, P, Flesch-Janys, D, Fasching, P A, Haeberle, L, Ekici, A B, Beckmann, M W, Burwinkel, B, Marme, F, Schneeweiss, A, Sohn, C, Trentham-Dietz, A, Newcomb, P, Titus, L, Egan, K M, Hunter, D J, Lindstrom, S, Tamimi, R M, Kraft, P, Rahman, N, Turnbull, C, Renwick, A, Seal, S, LI, J, Liu, J, Humphreys, K, Benitez, J, Pilar Zamora, M, Arias Perez, J I, Menéndez, P, Jakubowska, A, Lubinski, J, Jaworska-Bieniek, K, Durda, K, Bogdanova, N V, Antonenkova, N N, Dörk, T, Anton-Culver, H, Neuhausen, S L, Ziogas, A, Bernstein, L, Devilee, P, Tollenaar, R A E M, Seynaeve, C, Van Asperen, C J, Cox, A, Cross, S S, Reed, M, Khusnutdinova, E, Bermisheva, M, Prokofyeva, D, Takhirova, Z, Meindl, A, Schmutzler, R K, Sutter, C, Yang, R, Schürmann, P, Bremer, M, Christiansen, H, Park-Simon, T-W, Hillemanns, P, Guénel, P, Truong, T, Menegaux, F, Sanchez, M, Radice, P, Peterlongo, P, Manoukian, S, Pensotti, V, Hopper, J L, Tsimiklis, H, Apicella, C, Southey, M C, Brauch, H, Brűning, T, Ko, Y-D, Sigurdson, A J, Doody, M M, Hamann, U, Torres, D, Ulmer, H-U, Försti, A, Sawyer, E J, Tomlinson, I, Kerin, M J, Miller, N, Andrulis, I L, Knight, J A, Glendon, G, Marie Mulligan, A, Chenevix-Trench, G, Balleine, R, Giles, G G, Milne, R L, McLean, C, Lindblom, A, Margolin, S, Haiman, C A, Henderson, B E, Schumacher, F, Le Marchand, L, Eilber, U, Wang-Gohrke, S, Hooning, M J, Hollestelle, A, Van Den Ouweland, A M W, Koppert, L B, Carpenter, J, Clarke, C, Scott, R, Mannermaa, A, Kataja, V, Kosma, V-M, Hartikainen, J M, Brenner, H, Arndt, V, Stegmaier, C, Karina Dieffenbach, A, Winqvist, R, Pylkäs, K, Jukkola-Vuorinen, A, Grip, M, Offit, K, Vijai, J, Robson, M, Rau-Murthy, R, Dwek, M, Swann, R, Annie Perkins, K, Goldberg, M S, Labrèche, F, Dumont, M., Eccles, D M, Tapper, W J, Rafiq, S, John, E M, Whittemore, A S, Slager, S, Yannoukakos, D, Toland, A E, Yao, S, Zheng, W, Halverson, S L, González-Neira, A, Pita, G, Rosario Alonso, M, Álvarez, N, Herrero, D, Tessier, D C, Vincent, D, Bacot, F, Luccarini, C, Baynes, C, Ahmed, S, Maranian, M, Healey, C S, Simard, J, Hall, P, Easton, D F, Garcia-Closas, M

الوصف: Background: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking. Methods: We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates. Results: There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1 of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer. Conclusions: The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this report. © 2015 © The Author 2015. Published by Oxford University Press.

وصف الملف: application/pdf

العلاقة: http://sro.sussex.ac.uk/id/eprint/57924/1/JNCI%20J%20Natl%20Cancer%20Inst-2015-Mavaddat-.pdfTest; Mavaddat, N, Pharoah, P D P, Michailidou, K, Tyrer, J, Brook, M N, Bolla, M K, Wang, Q, Dennis, J, Dunning, A M, Shah, M, Luben, R, Brown, J, Bojesen, S E, Nordestgaard, B G, Nielsen, S F, Flyger, H, Czene, K, Darabi, H, Eriksson, M, Peto, J, Dos-Santos-Silva, I, Dudbridge, F, Johnson, N, Schmidt, M K, Broeks, A, Verhoef, S, Rutgers, E J, Swerdlow, A, Ashworth, A, Orr, N, Schoemaker, M J, Figueroa, J, Chanock, S J, Brinton, L, Lissowska, J, Couch, F J, Olson, J E, Vachon, C, Pankratz, V S, Lambrechts, D, Wildiers, H, Van Ongeval, C, Van Limbergen, E, Kristensen, V, Grenaker Alnæs, G, Nord, S, Borresen-Dale, A-L, Nevanlinna, H, Muranen, TA, Aittomäki, K, Blomqvist, C, Chang-Claude, J, Rudolph, A, Seibold, P, Flesch-Janys, D, Fasching, P A, Haeberle, L, Ekici, A B, Beckmann, M W, Burwinkel, B, Marme, F, Schneeweiss, A, Sohn, C, Trentham-Dietz, A, Newcomb, P, Titus, L, Egan, K M, Hunter, D J, Lindstrom, S, Tamimi, R M, Kraft, P, Rahman, N, Turnbull, C, Renwick, A, Seal, S, LI, J, Liu, J, Humphreys, K, Benitez, J, Pilar Zamora, M, Arias Perez, J I, Menéndez, P, Jakubowska, A, Lubinski, J, Jaworska-Bieniek, K, Durda, K, Bogdanova, N V, Antonenkova, N N, Dörk, T, Anton-Culver, H, Neuhausen, S L, Ziogas, A, Bernstein, L, Devilee, P, Tollenaar, R A E M, Seynaeve, C, Van Asperen, C J, Cox, A, Cross, S S, Reed, M, Khusnutdinova, E, Bermisheva, M, Prokofyeva, D, Takhirova, Z, Meindl, A, Schmutzler, R K, Sutter, C, Yang, R, Schürmann, P, Bremer, M, Christiansen, H, Park-Simon, T-W, Hillemanns, P, Guénel, P, Truong, T, Menegaux, F, Sanchez, M, Radice, P, Peterlongo, P, Manoukian, S, Pensotti, V, Hopper, J L, Tsimiklis, H, Apicella, C, Southey, M C, Brauch, H, Brűning, T, Ko, Y-D, Sigurdson, A J, Doody, M M, Hamann, U, Torres, D, Ulmer, H-U, Försti, A, Sawyer, E J, Tomlinson, I, Kerin, M J, Miller, N, Andrulis, I L, Knight, J A, Glendon, G, Marie Mulligan, A, Chenevix-Trench, G, Balleine, R, Giles, G G, Milne, R L, McLean, C, Lindblom, A, Margolin, S, Haiman, C A, Henderson, B E, Schumacher, F, Le Marchand, L, Eilber, U, Wang-Gohrke, S, Hooning, M J, Hollestelle, A, Van Den Ouweland, A M W, Koppert, L B, Carpenter, J, Clarke, C, Scott, R, Mannermaa, A, Kataja, V, Kosma, V-M, Hartikainen, J M, Brenner, H, Arndt, V, Stegmaier, C, Karina Dieffenbach, A, Winqvist, R, Pylkäs, K, Jukkola-Vuorinen, A, Grip, M, Offit, K, Vijai, J, Robson, M, Rau-Murthy, R, Dwek, M, Swann, R, Annie Perkins, K, Goldberg, M S, Labrèche, F, Dumont, M., Eccles, D M, Tapper, W J, Rafiq, S, John, E M, Whittemore, A S, Slager, S, Yannoukakos, D, Toland, A E, Yao, S, Zheng, W, Halverson, S L, González-Neira, A, Pita, G, Rosario Alonso, M, Álvarez, N, Herrero, D, Tessier, D C, Vincent, D, Bacot, F, Luccarini, C, Baynes, C, Ahmed, S, Maranian, M, Healey, C S, Simard, J, Hall, P, Easton, D F and Garcia-Closas, M (2015) Prediction of breast cancer risk based on profiling with common genetic variants. Journal of the National Cancer Institute, 107 (5). djv036. ISSN 0027-8874

الإتاحة: https://doi.org/10.1093/jnci/djv036Test
http://sro.sussex.ac.uk/id/eprint/57924Test/
http://sro.sussex.ac.uk/id/eprint/57924/1/JNCI%20J%20Natl%20Cancer%20Inst-2015-Mavaddat-.pdfTest

المؤلفون: Orr, N, Dudbridge, F, Dryden, N, Maguire, S, Novo, D, Perrakis, E, Johnson, N, Ghoussaini, M, Hopper, J L, Southey, M C, Apicella, C, Stone, J, Schmidt, M K, Broeks, A, Van't Veer, L J, Hogervorst, F B, Fasching, P A, Haeberle, L, Ekici, A B, Beckmann, M W, Gibson, L, Aitken, Z, Warren, H, Sawyer, E, Tomlinson, I, Kerin, M J, Miller, N, Burwinkel, B, Marme, F, Schneeweiss, A, Sohn, C, Guénel, P, Truong, T, Cordina-Duverger, E, Sanchez, M, Bojesen, S E, Nordestgaard, B G, Nielsen, S F, Flyger, H, Benitez, J, Zamora, M P, Perez, J I A, Menéndez, P, Anton-Culver, H, Neuhausen, S L, Brenner, H, Dieffenbach, A K, Arndt, V, Stegmaier, C, Hamann, U, Brauch, H, Justenhoven, C, Brűning, T, Ko, Y-D, Nevanlinna, H, Aittomki, K, Blomqvist, C, Khan, S, Bogdanova, N, Dörk, T, Lindblom, A, Margolin, S, Mannermaa, A, Kataja, V, Kosma, V-M, Hartikainen, J M, Chenevix-Trench, G, Beesley, J, Lambrechts, D, Moisse, M, Floris, G, Beuselinck, B, Chang-Claude, J, Rudolph, A, Seibold, P, Flesch-Janys, D, Radice, P, Peterlongo, P, Peissel, B, Pensotti, V, Couch, F J, Olson, J E, Slettedahl, S, Vachon, C, Giles, G G, Milne, R L, McLean, C, Haiman, C A, Henderson, B E, Schumacher, F, Le Marchand, L, Simard, J, Goldberg, M S, Labrèche, F, Dumont, M, Kristensen, V, Alnæs, G G, Nord, S, Borresen-Dale, A-L, Zheng, W, Deming-Halverson, S, Shrubsole, M, Long, J, Winqvist, R, Pylkäs, K, Jukkola-Vuorinen, A, Grip, M, Andrulis, I L, Knight, J A, Glendon, G, Tchatchou, S, Devilee, P, Tollenaar, R A E M, Seynaeve, C M, Van Asperen, C J, Garcia-Closas, M, Figueroa, J., Chanock, S.J., Lissowska, J, Czene, K, Darabi, H, Eriksson, M, Klevebring, D, Hooning, M J, Hollestelle, A, Van Deurzen, C H M, Kriege, M, Hall, P, Li, J, Liu, J, Humphreys, K, Cox, A, Cross, S S, Reed, M, Pharoah, P D P, Dunning, A M, Shah, M, Perkins, B J, Jakubowska, A, Lubinski, J, Jaworska-Bieniek, K, Durda, K, Ashworth, A, Swerdlow, A, Jones, M, Schoemaker, M J, Meindl, A, Schmutzler, R K, Olswold, C, Slager, S, Toland, A E, Yannoukakos, D, Muir, K, Lophatananon, A, Stewart-Brown, S, Siriwanarangsan, P, Matsuo, K, Ito, H, Iwata, H, Ishiguro, J, Wu, A H, Tseng, C-C, Van Den Berg, D, Stram, D O, Teo, S H, Yip, C H, Kang, P, Ikram, M K, Shu, X-O, Lu, W, Gao, Y-T, Cai, H, Kang, D, Choi, J-Y, Park, S K, Noh, D-Y, Hartman, M, Miao, H, Lim, W Y, Lee, S C, Sangrajrang, S, Gaborieau, V, Brennan, P, Mckay, J, Wu, P-E, Hou, M-F, Yu, J-C, Shen, C-Y, Blot, W., Cai, Q., Signorello, L B, Luccarini, C, Bayes, C, Ahmed, S, Maranian, M, Healey, C S, González-Neira, A, Pita, G, Rosario Alonso, M, Álvarez, N, Herrero, D, Tessier, D C, Vincent, D, Bacot, F, Hunter, D J, Lindstrom, S, Dennis, J, Michailidou, K, Bolla, M K, Easton, D F, Dos Santos Silva, I, Fletcher, O, Peto, J

الوصف: We recently identified a novel susceptibility variant, rs865686, for estrogen-receptor positive breast cancer at 9q31.2. Here, we report a fine-mapping analysis of the 9q31.2 susceptibility locus using 43 160 cases and 42 600 controls of European ancestry ascertained from 52 studies and a further 5795 cases and 6624 controls of Asian ancestry from nine studies. Single nucleotide polymorphism (SNP) rs676256 was most strongly associated with risk in Europeans (odds ratios OR = 0.90 0.88-0.92; P-value = 1.58 × 10-25). This SNP is one of a cluster of highly correlated variants, including rs865686, that spans ~14.5 kb. We identified two additional independent association signals demarcated by SNPs rs10816625 (OR = 1.12 1.08-1.17; P-value = 7.89 × 10-09) and rs13294895 (OR = 1.09 1.06-1.12; P-value = 2.97 × 10-11). SNP rs10816625, but not rs13294895, was also associated with risk of breast cancer in Asian individuals (OR = 1.12 1.06-1.18; P-value = 2.77 × 10-05). Functional genomic annotation using data derived from breast cancer cell-line models indicates that these SNPs localise to putative enhancer elements that bind known drivers of hormone-dependent breast cancer, including ER-a, FOXA1 and GATA-3. In vitro analyses indicate that rs10816625 and rs13294895 have allele-specific effects on enhancer activity and suggest chromatin interactions with the KLF4 gene locus. These results demonstrate the power of dense genotyping in large studies to identify independent susceptibility variants. Analysis of associations using subjects with different ancestry, combined with bioinformatic and genomic characterisation, can provide strong evidence for the likely causative alleles and their functional basis. © The Author 2015. Published by Oxford University Press. All rights reserved.

وصف الملف: application/pdf

العلاقة: http://sro.sussex.ac.uk/id/eprint/57925/1/Hum.%20Mol.%20Genet.-2015-Orr-2966-84.pdfTest; Orr, N, Dudbridge, F, Dryden, N, Maguire, S, Novo, D, Perrakis, E, Johnson, N, Ghoussaini, M, Hopper, J L, Southey, M C, Apicella, C, Stone, J, Schmidt, M K, Broeks, A, Van't Veer, L J, Hogervorst, F B, Fasching, P A, Haeberle, L, Ekici, A B, Beckmann, M W, Gibson, L, Aitken, Z, Warren, H, Sawyer, E, Tomlinson, I, Kerin, M J, Miller, N, Burwinkel, B, Marme, F, Schneeweiss, A, Sohn, C, Guénel, P, Truong, T, Cordina-Duverger, E, Sanchez, M, Bojesen, S E, Nordestgaard, B G, Nielsen, S F, Flyger, H, Benitez, J, Zamora, M P, Perez, J I A, Menéndez, P, Anton-Culver, H, Neuhausen, S L, Brenner, H, Dieffenbach, A K, Arndt, V, Stegmaier, C, Hamann, U, Brauch, H, Justenhoven, C, Brűning, T, Ko, Y-D, Nevanlinna, H, Aittomki, K, Blomqvist, C, Khan, S, Bogdanova, N, Dörk, T, Lindblom, A, Margolin, S, Mannermaa, A, Kataja, V, Kosma, V-M, Hartikainen, J M, Chenevix-Trench, G, Beesley, J, Lambrechts, D, Moisse, M, Floris, G, Beuselinck, B, Chang-Claude, J, Rudolph, A, Seibold, P, Flesch-Janys, D, Radice, P, Peterlongo, P, Peissel, B, Pensotti, V, Couch, F J, Olson, J E, Slettedahl, S, Vachon, C, Giles, G G, Milne, R L, McLean, C, Haiman, C A, Henderson, B E, Schumacher, F, Le Marchand, L, Simard, J, Goldberg, M S, Labrèche, F, Dumont, M, Kristensen, V, Alnæs, G G, Nord, S, Borresen-Dale, A-L, Zheng, W, Deming-Halverson, S, Shrubsole, M, Long, J, Winqvist, R, Pylkäs, K, Jukkola-Vuorinen, A, Grip, M, Andrulis, I L, Knight, J A, Glendon, G, Tchatchou, S, Devilee, P, Tollenaar, R A E M, Seynaeve, C M, Van Asperen, C J, Garcia-Closas, M, Figueroa, J., Chanock, S.J., Lissowska, J, Czene, K, Darabi, H, Eriksson, M, Klevebring, D, Hooning, M J, Hollestelle, A, Van Deurzen, C H M, Kriege, M, Hall, P, Li, J, Liu, J, Humphreys, K, Cox, A, Cross, S S, Reed, M, Pharoah, P D P, Dunning, A M, Shah, M, Perkins, B J, Jakubowska, A, Lubinski, J, Jaworska-Bieniek, K, Durda, K, Ashworth, A, Swerdlow, A, Jones, M, Schoemaker, M J, Meindl, A, Schmutzler, R K, Olswold, C, Slager, S, Toland, A E, Yannoukakos, D, Muir, K, Lophatananon, A, Stewart-Brown, S, Siriwanarangsan, P, Matsuo, K, Ito, H, Iwata, H, Ishiguro, J, Wu, A H, Tseng, C-C, Van Den Berg, D, Stram, D O, Teo, S H, Yip, C H, Kang, P, Ikram, M K, Shu, X-O, Lu, W, Gao, Y-T, Cai, H, Kang, D, Choi, J-Y, Park, S K, Noh, D-Y, Hartman, M, Miao, H, Lim, W Y, Lee, S C, Sangrajrang, S, Gaborieau, V, Brennan, P, Mckay, J, Wu, P-E, Hou, M-F, Yu, J-C, Shen, C-Y, Blot, W., Cai, Q., Signorello, L B, Luccarini, C, Bayes, C, Ahmed, S, Maranian, M, Healey, C S, González-Neira, A, Pita, G, Rosario Alonso, M, Álvarez, N, Herrero, D, Tessier, D C, Vincent, D, Bacot, F, Hunter, D J, Lindstrom, S, Dennis, J, Michailidou, K, Bolla, M K, Easton, D F, Dos Santos Silva, I, Fletcher, O and Peto, J (2015) Fine-mapping identifies two additional breast cancer susceptibility loci at 9q31.2. Human Molecular Genetics, 24 (10). pp. 2966-2984. ISSN 0964-6906

الإتاحة: https://doi.org/10.1093/hmg/ddv035Test
http://sro.sussex.ac.uk/id/eprint/57925Test/
http://sro.sussex.ac.uk/id/eprint/57925/1/Hum.%20Mol.%20Genet.-2015-Orr-2966-84.pdfTest

المؤلفون: Litchfield, Kevin, Sultana, Razvan, Renwick, Anthony, Dudakia, Darshna, Seal, Sheila, Ramsay, Emma, Powell, Silvana, Elliott, Anna, Warren-Perry, Margaret, Eeles, Rosalind, Peto, Julian, Kote-Jarai, Zsofia, Muir, Kenneth, Nsengimana, Jeremie, UKTCC, Stratton, Michael R., Easton, Douglas F., Bishop, D. Timothy, Huddart, Robert A., Rahman, Nazneen, Turnbull, Clare, Pugh, J., Linger, R., Marke, J., Hughes, D., Pernet, D., Hall, P., Easton, D.F., Berchuck, A., Eeles, R., Chenevix-Trench, G., Dennis, J., Dunning, A.M., Lee, A., Dicks, E., Benitez, J., Gonzalez-Neira, A., Simard, J., Tessier, D.C., Bacot, F., Vincent, D., LaBoissière, S., Robidoux, F., Bojesen, S.E., Nielsen, S.F., Nordestgaard, B.G., Cunningham, J.M., Windebank, S.A., Hilker, C.A., Meyer, J.

مصطلحات موضوعية: ASSOCIATION STUDIES ARTICLES

الوصف: Recent genome-wide association studies (GWAS) and subsequent meta-analyses have identified over 25 SNPs at 18 loci, together accounting for >15% of the genetic susceptibility to testicular germ cell tumour (TGCT). To identify further common SNPs associated with TGCT, here we report a three-stage experiment, involving 4098 cases and 18 972 controls. Stage 1 comprised previously published GWAS analysis of 307 291 SNPs in 986 cases and 4946 controls. In Stage 2, we used previously published customised Illumina iSelect genotyping array (iCOGs) data across 694 SNPs in 1064 cases and 10 082 controls. Here, we report new genotyping of eight SNPs showing some evidence of association in combined analysis of Stage 1 and Stage 2 in an additional 2048 cases of TGCT and 3944 controls (Stage 3). Through fixed-effects meta-analysis across three stages, we identified a novel locus at 3q25.31 (rs1510272) demonstrating association with TGCT [per-allele odds ratio (OR) = 1.16, 95% confidence interval (CI) = 1.06–1.27; P = 1.2 × 10−9].

وصف الملف: text/html

العلاقة: http://hmg.oxfordjournals.org/cgi/content/short/24/4/1169Test; http://dx.doi.org/10.1093/hmg/ddu511Test

الإتاحة: https://doi.org/10.1093/hmg/ddu511Test
http://hmg.oxfordjournals.org/cgi/content/short/24/4/1169Test

المؤلفون: Mavaddat, N., Pharoah, P.D.P., Michailidou, K., Tyrer, J., Brook, M.N., Bolla, M.K., Wang, Q., Dennis, J., Dunning, A.M., Shah, M., Luben, R., Brown, J.C.C., Bojesen, S.E., Nordestgaard, B.G., Nielsen, S.F., Flyger, H., Czene, K., Darabi, H., Eriksson, M., Peto, J., Dos-Santos-Silva, I., Dudbridge, F., Johnson, N., Schmidt, M.K., Broeks, A., Verhoef, S., Rutgers, E.J., Swerdlow, A.J., Ashworth, A., Orr, N., Schoemaker, M.J., Figueroa, J.D., Chanock, S.J., Brinton, L., Lissowska, J., Couch, F.J., Olson, J.E., Vachon, C., Pankratz, V.S., Lambrechts, D., Wildiers, H., Van Ongeval, C., van Limbergen, E., Kristensen, V., Grenaker Alnaes, G., Nord, S., Borresen-Dale, A.-L., Nevanlinna, H., Muranen, T.A., Aittomaki, K., Blomqvist, C., Chang-Claude, J., Rudolph, A., Seibold, P., Flesch-Janys, D., Fasching, P.A., Haeberle, L., Ekici, A.B., Beckmann, M.W., Burwinkel, B., Marme, F., Schneeweiss, A., Sohn, C., Trentham-Dietz, A., Newcomb, P., Titus, L., Egan, K.M., Hunter, D.J., Lindstrom, S., Tamimi, R.M., Kraft, P., Rahman, N., Turnbull, C., Renwick, A., Seal, S., Li, J., Liu, J., Humphreys, K., Benitez, J., Pilar Zamora, M., Arias Perez, J.I., Menéndez, P., Jakubowska, A., Lubinski, J., Jaworska-Bieniek, K., Durda, K., Bogdanova, N.V., Antonenkova, N.N., Dörk, T., Anton-Culver, H., Neuhausen, S.L., Ziogas, A., Bernstein, L., Devilee, P., Tollenaar, R.A.E.M., Seynaeve, C., van Asperen, C.J., Cox, A., Cross, S.S., Reed, M.W., Khusnutdinova, E., Bermisheva, M., Prokofyeva, D., Takhirova, Z., Meindl, A., Schmutzler, R.K., Sutter, C., Yang, R., Schürmann, P., Bremer, M., Christiansen, H., Park-Simon, T.-W., Hillemanns, P., Guenel, P., Truong, T., Menegaux, F., Sanchez, M., Radice, P., Peterlongo, P., Manoukian, S., Pensotti, V., Hopper, J.L., Tsimiklis, H., Apicella, C., Southey, M.C., Brauch, H., Brüning, T., Ko, Y.-D., Sigurdson, A.J., Doody, M.M., Hamann, U., Torres, D., Ulmer, H.U., Försti, A., Sawyer, E., Tomlinson, I., Kerin, M.J., Miller, N., Andrulis, I.L., Knight, J.A., Glendon, G., Marie Mulligan, A., Chenevix-Trench, G., Balleine, R., Giles, G.G., Milne, R.L., McLean, C.A., Lindblom, A., Margolin, S., Haiman, C.A., Henderson, B.E., Schumacher, F., Le Marchand, L., Eilber, U., Wang-Gohrke, S., Hooning, M.J., Hollestelle, A., van den Ouweland, A.M.W., Koppert, L.B., Carpenter, J., Clarke, C., Scott, R., Mannermaa, A., Kataja, V., Kosma, V.-M., Hartikainen, J.M., Brenner, H., Arndt, V., Stegmaier, C., Karina Dieffenbach, A., Winqvist, R., Pylkas, K., Jukkola-Vuorinen, A., Grip, M., Offit, K., Vijai, J., Robson, M., Rau-Murthy, R., Dwek, M., Swann, R., Annie Perkins, K., Goldberg, M.S., Labrèche, F., Dumont, M., Eccles, D.M., Tapper, W.J., Rafiq, S., John, E.M., Whittemore, A.S., Slager, S., Yannoukakos, D., Toland, A.E., Yao, S., Zheng, W., Halverson, S.L., Gonzalez-Neira, A., Pita, G., Rosario Alonso, M., Álvarez, N., Herrero, D., Tessier, D.C., Vincent, D., Bacot, F., Luccarini, C., Baynes, C., Ahmed, S., Maranian, M., Healey, C.S., Simard, J., Hall, P., Easton, D.F., Garcia-Closas, M., Dos Santos Silva, I., Channock, S.J., Zamora, M.P., Ignacio Arias Perez, J., Neuhasen, S.L., Prokofieva, D., Mulligan, A.M., Halman, C.A., Dieffenbach, A.K., Perkins, K.A., Alonso, M.R.

مصطلحات موضوعية: Adult Aged Breast Neoplasms/chemistry Breast Neoplasms/epidemiology* Breast Neoplasms/genetics* Europe/epidemiology Female Gene Expression Profiling* Gene Expression Regulation, Neoplastic Genetic Predisposition to Disease Genotype Humans Middle Aged Odds Ratio Polymorphism, Single Nucleotide* Predictive Value of Tests Receptors, Estrogen/analysis Risk Assessment Risk Factors Tumor Markers, Biological/analysis

الوصف: BACKGROUND: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking. METHODS: We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates. RESULTS: There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1% of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer. CONCLUSIONS: The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this report.

وصف الملف: application/pdf

العلاقة: https://westminsterresearch.westminster.ac.uk/download/8bb2844a889c31be9b2a82b7a53e9bce937f2d2f8265ce6a43ec1f6ab780c749/5347008/Mavaddat_etal_JNCI_2015.pdfTest; https://doi.org/10.1093/jnci/djv036Test; Mavaddat, N., Pharoah, P.D.P., Michailidou, K., Tyrer, J., Brook, M.N., Bolla, M.K., Wang, Q., Dennis, J., Dunning, A.M., Shah, M., Luben, R., Brown, J.C.C., Bojesen, S.E., Nordestgaard, B.G., Nielsen, S.F., Flyger, H., Czene, K., Darabi, H., Eriksson, M., Peto, J., Dos-Santos-Silva, I., Dudbridge, F., Johnson, N., Schmidt, M.K., Broeks, A., Verhoef, S., Rutgers, E.J., Swerdlow, A.J., Ashworth, A., Orr, N., Schoemaker, M.J., Figueroa, J.D., Chanock, S.J., Brinton, L., Lissowska, J., Couch, F.J., Olson, J.E., Vachon, C., Pankratz, V.S., Lambrechts, D., Wildiers, H., Van Ongeval, C., van Limbergen, E., Kristensen, V., Grenaker Alnaes, G., Nord, S., Borresen-Dale, A.-L., Nevanlinna, H., Muranen, T.A., Aittomaki, K., Blomqvist, C., Chang-Claude, J., Rudolph, A., Seibold, P., Flesch-Janys, D., Fasching, P.A., Haeberle, L., Ekici, A.B., Beckmann, M.W., Burwinkel, B., Marme, F., Schneeweiss, A., Sohn, C., Trentham-Dietz, A., Newcomb, P., Titus, L., Egan, K.M., Hunter, D.J., Lindstrom, S., Tamimi, R.M., Kraft, P., Rahman, N., Turnbull, C., Renwick, A., Seal, S., Li, J., Liu, J., Humphreys, K., Benitez, J., Pilar Zamora, M., Arias Perez, J.I., Menéndez, P., Jakubowska, A., Lubinski, J., Jaworska-Bieniek, K., Durda, K., Bogdanova, N.V., Antonenkova, N.N., Dörk, T., Anton-Culver, H., Neuhausen, S.L., Ziogas, A., Bernstein, L., Devilee, P., Tollenaar, R.A.E.M., Seynaeve, C., van Asperen, C.J., Cox, A., Cross, S.S., Reed, M.W., Khusnutdinova, E., Bermisheva, M., Prokofyeva, D., Takhirova, Z., Meindl, A., Schmutzler, R.K., Sutter, C., Yang, R., Schürmann, P., Bremer, M., Christiansen, H., Park-Simon, T.-W., Hillemanns, P., Guenel, P., Truong, T., Menegaux, F., Sanchez, M., Radice, P., Peterlongo, P., Manoukian, S., Pensotti, V., Hopper, J.L., Tsimiklis, H., Apicella, C., Southey, M.C., Brauch, H., Brüning, T., Ko, Y.-D., Sigurdson, A.J., Doody, M.M., Hamann, U., Torres, D., Ulmer, H.U., Försti, A., Sawyer, E., Tomlinson, I., Kerin, M.J., Miller, N., Andrulis, I.L., Knight, J.A., Glendon, G., Marie Mulligan, A., Chenevix-Trench, G., Balleine, R., Giles, G.G., Milne, R.L., McLean, C.A., Lindblom, A., Margolin, S., Haiman, C.A., Henderson, B.E., Schumacher, F., Le Marchand, L., Eilber, U., Wang-Gohrke, S., Hooning, M.J., Hollestelle, A., van den Ouweland, A.M.W., Koppert, L.B., Carpenter, J., Clarke, C., Scott, R., Mannermaa, A., Kataja, V., Kosma, V.-M., Hartikainen, J.M., Brenner, H., Arndt, V., Stegmaier, C., Karina Dieffenbach, A., Winqvist, R., Pylkas, K., Jukkola-Vuorinen, A., Grip, M., Offit, K., Vijai, J., Robson, M., Rau-Murthy, R., Dwek, M., Swann, R., Annie Perkins, K., Goldberg, M.S., Labrèche, F., Dumont, M., Eccles, D.M., Tapper, W.J., Rafiq, S., John, E.M., Whittemore, A.S., Slager, S., Yannoukakos, D., Toland, A.E., Yao, S., Zheng, W., Halverson, S.L., Gonzalez-Neira, A., Pita, G., Rosario Alonso, M., Álvarez, N., Herrero, D., Tessier, D.C., Vincent, D., Bacot, F., Luccarini, C., Baynes, C., Ahmed, S., Maranian, M., Healey, C.S., Simard, J., Hall, P., Easton, D.F., Garcia-Closas, M., Dos Santos Silva, I., Channock, S.J., Zamora, M.P., Ignacio Arias Perez, J., Neuhasen, S.L., Prokofieva, D., Mulligan, A.M., Halman, C.A., Dieffenbach, A.K., Perkins, K.A. and Alonso, M.R. 2015. Prediction of breast cancer risk based on profiling with common genetic variants. Journal of the National Cancer Institute. 107 (5). https://doi.org/10.1093/jnci/djv036Test

الإتاحة: https://doi.org/10.1093/jnci/djv036Test
https://westminsterresearch.westminster.ac.uk/item/96xyy/prediction-of-breast-cancer-risk-based-on-profiling-with-common-genetic-variantsTest
https://westminsterresearch.westminster.ac.uk/download/8bb2844a889c31be9b2a82b7a53e9bce937f2d2f8265ce6a43ec1f6ab780c749/5347008/Mavaddat_etal_JNCI_2015.pdfTest

المؤلفون: Lin, W-Y, Camp, N J, Ghoussaini, M, Beesley, J, Michailidou, K, Hopper, J L, Apicella, C, Southey, M C, Stone, J, Schmidt, M K, Broeks, A, Van't Veer, L J, Th Rutgers, E J, Muir, K, Lophatananon, A, Stewart-Brown, S, Siriwanarangsan, P, Fasching, P A, Haeberle, L, Ekici, A B, Beckmann, M W, Peto, J, Dos-Santos-Silva, I, Fletcher, O, Johnson, N, Bolla, M K, Wang, Q, Dennis, J, Sawyer, E J, Cheng, T, Tomlinson, I, Kerin, M J, Miller, N, Marmé, F, Surowy, H M, Burwinkel, B, Guénel, P, Truong, T, Menegaux, F, Mulot, C, Bojesen, S E, Nordestgaard, B G, Nielsen, S F, Flyger, H, Benitez, J, Pilar Zamora, M, Perez, J I A, Menéndez, P, González-Neira, A, Pita, G, Rosario Alonso, M, Álvarez, N, Herrero, D, Anton-Culver, H, Brenner, H, Dieffenbach, A K, Arndt, V, Stegmaier, C, Meindl, A, Lichtner, P, Schmutzler, R K, Müller-Myhsok, B, Brauch, H, Brűning, T, Ko, Y-D, Tessier, D C, Vincent, D, Bacot, F, Nevanlinna, H, Aittomäki, K, Blomqvist, C, Khan, S, Matsuo, K, Ito, H, Iwata, H, Horio, A, Bogdanova, N V, Antonenkova, N N, Dörk, T, Lindblom, A, Margolin, S, Mannermaa, A, Kataja, V, Kosma, V-M, Hartikainen, J M, Wu, A H, Tseng, C-C, Van Den Berg, D, Stram, D O, Neven, P, Wauters, E, Wildiers, H, Lambrechts, D, Chang-Claude, J, Rudolph, A, Seibold, P, Flesch-Janys, D, Radice, P, Peterlongo, P, Manoukian, S, Bonanni, B, Couch, F J, Wang, X, Vachon, C, Purrington, K, Giles, G G, Milne, R L, Mclean, C, Haiman, C A, Henderson, B E, Schumacher, F, Marchand, L L, Simard, J, Goldberg, M S, Labrèche, F, Dumont, M, Teo, S H, Yip, C H, Hassan, N, Vithana, E N, Kristensen, V, Zheng, W, Deming-Halverson, S, Shrubsole, M J, Long, J, Winqvist, R, Pylkäs, K, Jukkola-Vuorinen, A, Kauppila, S, Andrulis, I L, Knight, J A, Glendon, G, Tchatchou, S, Devilee, P, Tollenaar, R A E M, Seynaeve, C, Van Asperen, C J, García-Closas, M, Figueroa, J, Lissowska, J, Brinton, L, Czene, K, Darabi, H, Eriksson, M, Brand, J S, Hooning, M J, Hollestelle, A, Van DenOuweland, A M W, Jager, A, Li, J, Liu, J, Humphreys, K, Shu, X-O, Lu, W, Gao, Y T, Cai, H, Cross, S S, Reed, M, Blot, W, Signorello, L B, Cai, Q, Pharoah, P D P, Perkins, B, Shah, M, Blows, F M, Kang, D, Yoo, K-Y, Noh, D-Y, Hartman, M, Miao, H, Chia, K S, Putti, T C, Hamann, U, Luccarini, C, Baynes, C, Ahmed, S, Maranian, M, Healey, C S, Jakubowska, A, Lubinski, J, Jaworska-Bieniek, K, Durda, K, Sangrajrang, S, Gaborieau, V, Brennan, P, Mckay, J, Slager, S, Toland, A E, Yannoukakos, D, Shen, C-Y, Hsiung, C-N, Wu, P-E, Ding, S-L, Ashworth, A, Jones, M, Orr, N, Swerdlow, A J, Tsimiklis, H, Makalic, E, Schmidt, D F, Bui, Q M, Chanock, S J, Hunter, D J, Hein, R, Dahmen, N, Beckmann, L, Aaltonen, K, Muranen, T A, Heikkinen, T, Irwanto, A, Rahman, N, Turnbull, C A, Waisfisz, Q, Meijers-Heijboer, H E J, Adank, M A, Van Der Luijt, R B, Hall, P, Chenevix-Trench, G, Dunning, A, Easton, D F, Cox, A

الوصف: Previous studies have suggested that polymorphisms in CASP8 on chromosome 2 are associated with breast cancer risk. To clarify the role of CASP8 in breast cancer susceptibility, we carried out dense genotyping of this region in the Breast Cancer Association Consortium (BCAC). Single-nucleotide polymorphisms (SNPs) spanning a 1 Mb region around CASP8 were genotyped in 46 450 breast cancer cases and 42 600 controls of European origin from 41 studies participating in the BCAC as part of a custom genotyping array experiment (iCOGS). Missing genotypes and SNPs were imputed and, after quality exclusions, 501 typed and 1232 imputed SNPs were included in logistic regressionmodels adjusting for study and ancestry principal components. The SNPs retained in the final model were investigated further in data from nine genome-wide association studies (GWAS) comprising in total 10 052 case and 12 575 control subjects. The most significant association signal observed in European subjects was for the imputed intronic SNP rs1830298 in ALS2CR12 (telomeric to CASP8), with per allele odds ratio and 95 confidence interval OR (95% confidence interval, CI) for the minor allele of 1.05 (1.03-1.07), P = 1 × 10-5. Three additional independent signals from intronic SNPs were identified, in CASP8 (rs36043647), ALS2CR11 (rs59278883) and CFLAR (rs7558475). The association with rs1830298 was replicated in the imputed results from the combined GWAS (P=3 × 10-6), yielding a combined OR (95% CI) of 1.06 (1.04-1.08), P = 1 × 10-9. Analyses of gene expression associations in peripheral blood and normal breast tissue indicate that CASP8might be the target gene, suggesting amechanism involving apoptosis. © The Author 2014.

العلاقة: Lin, W-Y, Camp, N J, Ghoussaini, M, Beesley, J, Michailidou, K, Hopper, J L, Apicella, C, Southey, M C, Stone, J, Schmidt, M K, Broeks, A, Van't Veer, L J, Th Rutgers, E J, Muir, K, Lophatananon, A, Stewart-Brown, S, Siriwanarangsan, P, Fasching, P A, Haeberle, L, Ekici, A B, Beckmann, M W, Peto, J, Dos-Santos-Silva, I, Fletcher, O, Johnson, N, Bolla, M K, Wang, Q, Dennis, J, Sawyer, E J, Cheng, T, Tomlinson, I, Kerin, M J, Miller, N, Marmé, F, Surowy, H M, Burwinkel, B, Guénel, P, Truong, T, Menegaux, F, Mulot, C, Bojesen, S E, Nordestgaard, B G, Nielsen, S F, Flyger, H, Benitez, J, Pilar Zamora, M, Perez, J I A, Menéndez, P, González-Neira, A, Pita, G, Rosario Alonso, M, Álvarez, N, Herrero, D, Anton-Culver, H, Brenner, H, Dieffenbach, A K, Arndt, V, Stegmaier, C, Meindl, A, Lichtner, P, Schmutzler, R K, Müller-Myhsok, B, Brauch, H, Brűning, T, Ko, Y-D, Tessier, D C, Vincent, D, Bacot, F, Nevanlinna, H, Aittomäki, K, Blomqvist, C, Khan, S, Matsuo, K, Ito, H, Iwata, H, Horio, A, Bogdanova, N V, Antonenkova, N N, Dörk, T, Lindblom, A, Margolin, S, Mannermaa, A, Kataja, V, Kosma, V-M, Hartikainen, J M, Wu, A H, Tseng, C-C, Van Den Berg, D, Stram, D O, Neven, P, Wauters, E, Wildiers, H, Lambrechts, D, Chang-Claude, J, Rudolph, A, Seibold, P, Flesch-Janys, D, Radice, P, Peterlongo, P, Manoukian, S, Bonanni, B, Couch, F J, Wang, X, Vachon, C, Purrington, K, Giles, G G, Milne, R L, Mclean, C, Haiman, C A, Henderson, B E, Schumacher, F, Marchand, L L, Simard, J, Goldberg, M S, Labrèche, F, Dumont, M, Teo, S H, Yip, C H, Hassan, N, Vithana, E N, Kristensen, V, Zheng, W, Deming-Halverson, S, Shrubsole, M J, Long, J, Winqvist, R, Pylkäs, K, Jukkola-Vuorinen, A, Kauppila, S, Andrulis, I L, Knight, J A, Glendon, G, Tchatchou, S, Devilee, P, Tollenaar, R A E M, Seynaeve, C, Van Asperen, C J, García-Closas, M, Figueroa, J, Lissowska, J, Brinton, L, Czene, K, Darabi, H, Eriksson, M, Brand, J S, Hooning, M J, Hollestelle, A, Van DenOuweland, A M W, Jager, A, Li, J, Liu, J, Humphreys, K, Shu, X-O, Lu, W, Gao, Y T, Cai, H, Cross, S S, Reed, M, Blot, W, Signorello, L B, Cai, Q, Pharoah, P D P, Perkins, B, Shah, M, Blows, F M, Kang, D, Yoo, K-Y, Noh, D-Y, Hartman, M, Miao, H, Chia, K S, Putti, T C, Hamann, U, Luccarini, C, Baynes, C, Ahmed, S, Maranian, M, Healey, C S, Jakubowska, A, Lubinski, J, Jaworska-Bieniek, K, Durda, K, Sangrajrang, S, Gaborieau, V, Brennan, P, Mckay, J, Slager, S, Toland, A E, Yannoukakos, D, Shen, C-Y, Hsiung, C-N, Wu, P-E, Ding, S-L, Ashworth, A, Jones, M, Orr, N, Swerdlow, A J, Tsimiklis, H, Makalic, E, Schmidt, D F, Bui, Q M, Chanock, S J, Hunter, D J, Hein, R, Dahmen, N, Beckmann, L, Aaltonen, K, Muranen, T A, Heikkinen, T, Irwanto, A, Rahman, N, Turnbull, C A, Waisfisz, Q, Meijers-Heijboer, H E J, Adank, M A, Van Der Luijt, R B, Hall, P, Chenevix-Trench, G, Dunning, A, Easton, D F and Cox, A (2015) Identification and characterization of novel associations in the CASP8/ALS2CR12 region on chromosome 2 with breast cancer risk. Human Molecular Genetics, 24 (1). pp. 285-298. ISSN 0964-6906

الإتاحة: https://doi.org/10.1093/hmg/ddu431Test
http://sro.sussex.ac.uk/id/eprint/57926Test/

المؤلفون: Orr N., Dudbridge F., Dryden N., Maguire S., Novo D., Perrakis E., Johnson N., Ghoussaini M., Hopper J.L., Southey M.C., Apicella C., Stone J., Schmidt M.K., Broeks A., Van't Veer L.J., Hogervorst F.B., Fasching P.A., Haeberle L., Ekici A.B., Beckmann M.W., Gibson L., Aitken Z., Warren H., Sawyer E., Tomlinson I., Kerin M.J., Miller N., Burwinkel B., Marme F., Schneeweiss A., Sohn C., Guenel P., Truong T., Cordina-Duverger E., Sanchez M., Bojesen S.E., Nordestgaard B.G., Nielsen S.F., Flyger H., Benitez J., Zamora M.P., Perez J.I.A., Menendez P., Anton-Culver H., Neuhausen S.L., Brenner H., Dieffenbach A.K., Arndt V., Stegmaier C., Hamann U., Brauch H., Justenhoven C., Bruning T., Ko Y.-D., Nevanlinna H., Aittomaki K., Blomqvist C., Khan S., Bogdanova N., Dork T., Lindblom A., Margolin S., Mannermaa A., Kataja V., Kosma V.-M., Hartikainen J.M., Chenevix-Trench G., Beesley J., Lambrechts D., Moisse M., Floris G., Beuselinck B., Chang-Claude J., Rudolph A., Seibold P., Flesch-Janys D., Radice P., Peterlongo P., Peissel B., Pensotti V., Couch F.J., Olson J.E., Slettedahl S., Vachon C., Giles G.G., Milne R.L., McLean C., Haiman C.A., Henderson B.E., Schumacher F., Le Marchand L., Simard J., Goldberg M.S., Labreche F., Dumont M., Kristensen V., Alnaes G.G., Nord S., Borresen-Dale A.-L., Zheng W., Deming-Halverson S., Shrubsole M., Long J., Winqvist R., Pylkas K., Jukkola-Vuorinen A., Grip M., Andrulis I.L., Knight J.A., Glendon G., Tchatchou S., Devilee P., Tollenaar R.A.E.M., Seynaeve C.M., Van Asperen C.J., Garcia-Closas M., Figueroa J., Chanock S.J., Lissowska J., Czene K., Darabi H., Eriksson M., Klevebring D., Hooning M.J., Hollestelle A., Van Deurzen C.H.M., Kriege M., Hall P., Li J., Liu J., Humphreys K., Cox A., Cross S.S., Reed M.W.R., Pharoah P.D.P., Dunning A.M., Shah M., Perkins B.J., Jakubowska A., Lubinski J., Jaworska-Bieniek K., Durda K., Ashworth A., Swerdlow A., Jones M., Schoemaker M.J., Meindl A., Schmutzler R.K., Olswold C., Slager S., Toland A.E., Yannoukakos D., Muir K., Lophatananon A., Stewart-Brown S., Siriwanarangsan P., Matsuo K., Ito H., Iwata H., Ishiguro J., Wu A.H., Tseng C.-C., Van Den Berg D., Stram D.O., Teo S.H., Yip C.H., Kang P., Mohammad Kamran Ikram, Shu X.-O., Lu W., Gao Y.-T., Cai H., Kang D., Choi J.-Y., Park S.K., Noh D.-Y., Hartman, Bo Anders Mikael, Miao, Hui, Lim, Wei-Yen, Lee, Soo Chin, Sangrajrang S., Gaborieau V., Brennan P., Mckay J., Wu P.-E., Hou M.-F., Yu J.-C., Shen C.-Y., Blot W., Cai Q., Signorello L.B., Luccarini C., Bayes C., Ahmed S., Maranian M., Healey C.S., Gonzalez-Neira A., Pita G., Rosario Alonso M., Alvarez N., Herrero D., Tessier D.C., Vincent D., Bacot F., Hunter D.J., Lindstrom S., Dennis J., Michailidou K., Bolla M.K., Easton D.F., Dos Santos Silva I., Fletcher O., Peto J.

المساهمون: DUKE-NUS GRADUATE MEDICAL SCHOOL S'PORE

الوصف: 10.1093/hmg/ddv035 ; Human Molecular Genetics ; 24 ; 10 ; 2966-2984

العلاقة: Orr N., Dudbridge F., Dryden N., Maguire S., Novo D., Perrakis E., Johnson N., Ghoussaini M., Hopper J.L., Southey M.C., Apicella C., Stone J., Schmidt M.K., Broeks A., Van't Veer L.J., Hogervorst F.B., Fasching P.A., Haeberle L., Ekici A.B., Beckmann M.W., Gibson L., Aitken Z., Warren H., Sawyer E., Tomlinson I., Kerin M.J., Miller N., Burwinkel B., Marme F., Schneeweiss A., Sohn C., Guenel P., Truong T., Cordina-Duverger E., Sanchez M., Bojesen S.E., Nordestgaard B.G., Nielsen S.F., Flyger H., Benitez J., Zamora M.P., Perez J.I.A., Menendez P., Anton-Culver H., Neuhausen S.L., Brenner H., Dieffenbach A.K., Arndt V., Stegmaier C., Hamann U., Brauch H., Justenhoven C., Bruning T., Ko Y.-D., Nevanlinna H., Aittomaki K., Blomqvist C., Khan S., Bogdanova N., Dork T., Lindblom A., Margolin S., Mannermaa A., Kataja V., Kosma V.-M., Hartikainen J.M., Chenevix-Trench G., Beesley J., Lambrechts D., Moisse M., Floris G., Beuselinck B., Chang-Claude J., Rudolph A., Seibold P., Flesch-Janys D., Radice P., Peterlongo P., Peissel B., Pensotti V., Couch F.J., Olson J.E., Slettedahl S., Vachon C., Giles G.G., Milne R.L., McLean C., Haiman C.A., Henderson B.E., Schumacher F., Le Marchand L., Simard J., Goldberg M.S., Labreche F., Dumont M., Kristensen V., Alnaes G.G., Nord S., Borresen-Dale A.-L., Zheng W., Deming-Halverson S., Shrubsole M., Long J., Winqvist R., Pylkas K., Jukkola-Vuorinen A., Grip M., Andrulis I.L., Knight J.A., Glendon G., Tchatchou S., Devilee P., Tollenaar R.A.E.M., Seynaeve C.M., Van Asperen C.J., Garcia-Closas M., Figueroa J., Chanock S.J., Lissowska J., Czene K., Darabi H., Eriksson M., Klevebring D., Hooning M.J., Hollestelle A., Van Deurzen C.H.M., Kriege M., Hall P., Li J., Liu J., Humphreys K., Cox A., Cross S.S., Reed M.W.R., Pharoah P.D.P., Dunning A.M., Shah M., Perkins B.J., Jakubowska A., Lubinski J., Jaworska-Bieniek K., Durda K., Ashworth A., Swerdlow A., Jones M., Schoemaker M.J., Meindl A., Schmutzler R.K., Olswold C., Slager S., Toland A.E., Yannoukakos D., Muir K., Lophatananon A., Stewart-Brown S., Siriwanarangsan P., Matsuo K., Ito H., Iwata H., Ishiguro J., Wu A.H., Tseng C.-C., Van Den Berg D., Stram D.O., Teo S.H., Yip C.H., Kang P., Mohammad Kamran Ikram, Shu X.-O., Lu W., Gao Y.-T., Cai H., Kang D., Choi J.-Y., Park S.K., Noh D.-Y., Hartman, Bo Anders Mikael, Miao, Hui, Lim, Wei-Yen, Lee, Soo Chin, Sangrajrang S., Gaborieau V., Brennan P., Mckay J., Wu P.-E., Hou M.-F., Yu J.-C., Shen C.-Y., Blot W., Cai Q., Signorello L.B., Luccarini C., Bayes C., Ahmed S., Maranian M., Healey C.S., Gonzalez-Neira A., Pita G., Rosario Alonso M., Alvarez N., Herrero D., Tessier D.C., Vincent D., Bacot F., Hunter D.J., Lindstrom S., Dennis J., Michailidou K., Bolla M.K., Easton D.F., Dos Santos Silva I., Fletcher O., Peto J. (2015). Fine-mapping identifies two additional breast cancer susceptibility loci at 9q31.2. Human Molecular Genetics 24 (10) : 2966-2984. ScholarBank@NUS Repository. https://doi.org/10.1093/hmg/ddv035Test; http://scholarbank.nus.edu.sg/handle/10635/123433Test; 000355326800022

الإتاحة: https://doi.org/10.1093/hmg/ddv035Test
http://scholarbank.nus.edu.sg/handle/10635/123433Test

المؤلفون: Mavaddat, N., Pharoah, P.D.P., Michailidou, K., Tyrer, J., Brook, M.N., Bolla, M.K., Wang, Q., Dennis, J., Dunning, A.M., Shah, M., Luben, R., Brown, J., Bojesen, S.E., Nordestgaard, B.G., Nielsen, S.F., Flyger, H., Czene, K., Darabi, H., Eriksson, M., Peto, J., dos-Santos-Silva, I., Dudbridge, F., Johnson, N., Schmidt, M.K., Broeks, A., Verhoef, S., Rutgers, E.J., Swerdlow, A., Ashworth, A., Orr, N., Schoemaker, M.J., Figueroa, J., Chanock, S.J., Brinton, L., Lissowska, J., Couch, F.J., Olson, J.E., Vachon, C., Pankratz, V.S., Lambrechts, D., Wildiers, H., Van Ongeval, C., Van Limbergen, E., Kristensen, V., Alnaes, G.G., Nord, S., Borresen-Dale, A.L., Nevanlinna, H., Muranen, T.A., Aittomaeki, K., Blomqvist, C., Chang-Claude, J., Rudolph, A., Seibold, P., Flesch-Janys, D., Fasching, P.A., Haeberle, L., Ekici, A.B., Beckmann, M.W., Burwinkel, B., Marme, F., Schneeweiss, A., Sohn, C., Trentham-Dietz, A., Newcomb, P., Titus, L., Egan, K.M., Hunter, D.J., Lindstrom, S., Tamimi, R.M., Kraft, P., Rahman, N., Turnbull, C., Renwick, A., Seal, S., Li, J., Liu, J., Humphreys, K., Benitez, J., Zamora, M.P., Perez, J.I.A., Menendez, P., Jakubowska, A., Lubinski, J., Jaworska-Bieniek, K., Durda, K., Bogdanova, N.V., Antonenkova, N.N., Doerk, T., Anton-Culver, H., Neuhausen, S.L., Ziogas, A., Bernstein, L., Devilee, P., Tollenaar, R.A.E.M., Seynaeve, C., van Asperen, C.J., Cox, A., Cross, S.S., Reed, M.W.R., Khusnutdinova, E., Bermisheva, M., Prokofyeva, D., Takhirova, Z., Meindl, A., Schmutzler, R.K., Sutter, C., Yang, R., Schuermann, P., Bremer, M., Christiansen, H., Park-Simon, T.W., Hillemanns, P., Guenel, P., Truong, T., Menegaux, F., Sanchez, M., Radice, P., Peterlongo, P., Manoukian, S., Pensotti, V., Hopper, J.L., Tsimiklis, H., Apicella, C., Southey, M.C., Brauch, H., Bruening, T., Ko, Y.D., Sigurdson, A.J., Doody, M.M., Hamann, U., Torres, D., Ulmer, H.U., Foersti, A., Sawyer, E.J., Tomlinson, I., Kerin, M.J., Miller, N., Andrulis, I.L., Knight, J.A., Glendon, G., Mulligan, A.M., Chenevix-Trench, G., Balleine, R., Giles, G.G., Milne, R.L., McLean, C., Lindblom, A., Margolin, S., Haiman, C.A., Henderson, B.E., Schumacher, F., Le Marchand, L., Eilber, U., Wang-Gohrke, S., Hooning, M.J., Hollestelle, A, van den Ouweland, A.M.W., Koppert, L.B., Carpenter, J., Clarke, C., Scott, R., Mannermaa, A., Kataja, V., Kosma, V.M., Hartikainen, J.M., Brenner, H., Arndt, V., Stegmaier, C., Dieffenbach, A.K., Winqvist, R., Pylkaes, K., Jukkola-Vuorinen, A., Grip, M., Offit, K., Vijai, J., Robson, M., Rau-Murthy, R., Dwek, M., Swann, R., Perkins, K.A., Goldberg, M.S., Labreche, F., Dumont, M., Eccles, D.M., Tapper, W.J., Rafiq, S., John, E.M., Whittemore, A.S., Slager, S., Yannoukakos, D., Toland, A.E., Yao, S., Zheng, W., Halverson, S.L., Gonzalez-Neira, A., Pita, G., Alonso, M.R., Alvarez, N., Herrero, D., Tessier, D.C., Vincent, D., Bacot, F., Luccarini, C., Baynes, C., Ahmed, S., Maranian, M., Healey, C.S., Simard, J., Hall, P., Easton, D.F., Garcia-Closas, M.

الوصف: Background: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking. Methods: We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates. Results: There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1% of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer. Conclusions: The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this report.

وصف الملف: text

العلاقة: https://eprints.whiterose.ac.uk/87271/1/wrro_87271.pdfTest; Mavaddat, N., Pharoah, P.D.P., Michailidou, K. et al. (209 more authors) (2015) Prediction of Breast Cancer Risk Based on Profiling With Common Genetic Variants. JNCI-Journal of the National Cancer Institute, 107 (5). ISSN 0027-8874

الإتاحة: https://doi.org/10.1093/jnci/djv036Test
https://eprints.whiterose.ac.uk/87271Test/
https://eprints.whiterose.ac.uk/87271/1/wrro_87271.pdfTest

المؤلفون: Orr, N., Dudbridge, F., Dryden, N., Maguire, S., Novo, D., Perrakis, E., Johnson, N., Ghoussaini, M., Hopper, J.L., Southey, M.C., Apicella, C., Stone, J., Schmidt, M.K., Broeks, A., Van't Veer, L.J., Hogervorst, F.B., Fasching, P.A., Haeberle, L., Ekici, A.B., Beckmann, M.W., Gibson, L., Aitken, Z., Warren, H., Sawyer, E., Tomlinson, I., Kerin, M.J., Miller, N., Burwinkel, B., Marme, F., Schneeweiss, A., Sohn, C., Guenel, P., Truong, T., Cordina-Duverger, E., Sanchez, M., Bojesen, S.E., Nordestgaard, B.G., Nielsen, S.F., Flyger, H., Benitez, J., Zamora, M.P., Perez, J.I.A., Menendez, P., Anton-Culver, H., Neuhausen, S.L., Brenner, H., Dieffenbach, A.K., Arndt, V., Stegmaier, C., Hamann, U., Brauch, H., Justenhoven, C., Bruning, T., Ko, Y.D., Nevanlinna, H., Aittomaki, K., Blomqvist, C., Khan, S., Bogdanova, N., Dork, T., Lindblom, A., Margolin, S., Mannermaa, A., Kataja, V., Kosma, V.M., Hartikainen, J.M., Chenevix-Trench, G., Beesley, J., Lambrechts, D., Moisse, M., Floris, G., Beuselinck, B., Chang-Claude, J., Rudolph, A., Seibold, P., Flesch-Janys, D., Radice, P., Peterlongo, P., Peissel, B., Pensotti, V., Couch, F.J., Olson, J.E., Slettedahl, S., Vachon, C., Giles, G.G., Milne, R.L., McLean, C., Haiman, C.A., Henderson, B.E., Schumacher, F., Le Marchand, L., Simard, J., Goldberg, M.S., Labreche, F., Dumont, M., Kristensen, V., Alnaes, G.G., Nord, S., Borresen-Dale, A.L., Zheng, W., Deming-Halverson, S., Shrubsole, M., Long, J., Winqvist, R., Pylkas, K., Jukkola-Vuorinen, A., Grip, M., Andrulis, I.L., Knight, J.A., Glendon, G., Tchatchou, S., Devilee, P., Tollenaar, R.A.E.M., Seynaeve, C.M., Van Asperen, C.J., Garcia-Closas, M., Figueroa, J., Chanock, S.J., Lissowska, J., Czene, K., Darabi, H., Eriksson, M., Klevebring, D., Hooning, M.J., Hollestelle, A., van Deurzen, C.H.M., Kriege, M., Hall, P., Li, J., Liu, J., Humphreys, K., Cox, A., Cross, S.S., Reed, M.W.R., Pharoah, P.D.P., Dunning, A.M., Shah, M., Perkins, B.J., Jakubowska, A., Lubinski, J., Jaworska-Bieniek, K., Durda, K., Ashworth, A., Swerdlow, A., Jones, M., Schoemaker, M.J., Meindl, A., Schmutzler, R.K., Olswold, C., Slager, S., Toland, A.E., Yannoukakos, D., Muir, K., Lophatananon, A., Stewart-Brown, S., Siriwanarangsan, P., Matsuo, K., Ito, H., Iwata, H., Ishiguro, J., Wu, A.H., Tseng, C.C., Van den Berg, D., Stram, D.O., Teo, S.H., Yip, C.H., Kang, P., Ikram, M.K., Shu, X.O., Lu, W., Gao, Y.T., Cai, H., Kang, D., Choi, J.Y., Park, S.K., Noh, D.Y., Hartman, M., Miao, H., Lim, W.Y., Lee, S.C., Sangrajrang, S., Gaborieau, V., Brennan, P., McKay, J., Wu, P.E., Hou, M.F., Yu, J.C., Shen, C.Y., Blot, W., Cai, Q., Signorello, L.B., Luccarini, C., Bayes, C., Ahmed, S., Maranian, M., Healey, C.S., Gonzalez-Neira, A., Pita, G., Alonso, M.R., Alvarez, N., Herrero, D., Tessier, D.C., Vincent, D., Bacot, F., Hunter, D.J., Lindstrom, S., Dennis, J., Michailidou, K., Bolla, M.K., Easton, D.F., Silva, I.D.S., Fletcher, O., Peto, J., Network, G.E.N.I.C.A., Investigators, K., Grp, A.O.C.S.

الوصف: We recently identified a novel susceptibility variant, rs865686, for estrogen-receptor positive breast cancer at 9q31.2. Here, we report a fine-mapping analysis of the 9q31.2 susceptibility locus using 43 160 cases and 42 600 controls of European ancestry ascertained from 52 studies and a further 5795 cases and 6624 controls of Asian ancestry from nine studies. Single nucleotide polymorphism (SNP) rs676256 was most strongly associated with risk in Europeans (odds ratios [OR] = 0.90 [0.88-0.92]; P-value = 1.58 × 10(-25)). This SNP is one of a cluster of highly correlated variants, including rs865686, that spans ∼14.5 kb. We identified two additional independent association signals demarcated by SNPs rs10816625 (OR = 1.12 [1.08-1.17]; P-value = 7.89 × 10(-09)) and rs13294895 (OR = 1.09 [1.06-1.12]; P-value = 2.97 × 10(-11)). SNP rs10816625, but not rs13294895, was also associated with risk of breast cancer in Asian individuals (OR = 1.12 [1.06-1.18]; P-value = 2.77 × 10(-05)). Functional genomic annotation using data derived from breast cancer cell-line models indicates that these SNPs localise to putative enhancer elements that bind known drivers of hormone-dependent breast cancer, including ER-α, FOXA1 and GATA-3. In vitro analyses indicate that rs10816625 and rs13294895 have allele-specific effects on enhancer activity and suggest chromatin interactions with the KLF4 gene locus. These results demonstrate the power of dense genotyping in large studies to identify independent susceptibility variants. Analysis of associations using subjects with different ancestry, combined with bioinformatic and genomic characterisation, can provide strong evidence for the likely causative alleles and their functional basis.

وصف الملف: text

العلاقة: https://eprints.whiterose.ac.uk/86075/1/WRRO_86075.pdfTest; Orr, N., Dudbridge, F., Dryden, N. et al. (213 more authors) (2015) Fine-mapping identifies two additional breast cancer susceptibility loci at 9q31.2. Human Molecular Genetics, 24 (10). 2966 - 2984. ISSN 0964-6906

الإتاحة: https://doi.org/10.1093/hmg/ddv035Test
https://eprints.whiterose.ac.uk/86075Test/
https://eprints.whiterose.ac.uk/86075/1/WRRO_86075.pdfTest

المؤلفون: Zheng, W., Zhang, B., Cai, Q., Sung, H., Michailidou, K., Shi, J., Choi, J.-Y., Long, J., Dennis, J., Humphreys, M. K., Wang, Q., Lu, W., Gao, Y.-T., Li, C., Cai, H., Park, S. K., Yoo, K.-Y., Noh, D.-Y., Han, W., Dunning, A. M., Benitez, J., Vincent, D., Bacot, F., Tessier, D., Kim, S.-W., Lee, M. H., Lee, J. W., Lee, J.-Y., Xiang, Y.-B., Zheng, Y., Wang, W., Ji, B.-T., Matsuo, K., Ito, Hidemi, Iwata, Hiroji, Tanaka, H., Wu, A. H., Tseng, C.-c., Van Den Berg, D., Stram, D. O., Teo, S. H., Yip, C. H., Kang, I. N., Wong, T. Y., Shen, C.-Y., Yu, J.-C., Huang, C.-S., Hou, M.-F., Hartman, M., Miao, H., Lee, S. C., Putti, T. C., Muir, Kenneth (Kenneth R.), Lophatananon, Artitaya, Stewart-Brown, Sarah L., Siriwanarangsan, P., Sangrajrang, S., Shen, H., Chen, K., Wu, P.-E., Ren, Z., Haiman, C. A., Sueta, A., Kim, M. K., Khoo, U. S., Iwasaki, M., Pharoah, P. D. P., Wen, W., Hall, P., Shu, X.-O., Easton, Douglas F., Kang, D.

الوصف: In a consortium including 23 637 breast cancer patients and 25 579 controls of East Asian ancestry, we investigated 70 single-nucleotide polymorphisms (SNPs) in 67 independent breast cancer susceptibility loci recently identified by genome-wide association studies (GWASs) conducted primarily in European-ancestry populations. SNPs in 31 loci showed an association with breast cancer risk at P < 0.05 in a direction consistent with that reported previously. Twenty-one of them remained statistically significant after adjusting for multiple comparisons with the Bonferroni-corrected significance level of <0.0015. Eight of the 70 SNPs showed a significantly different association with breast cancer risk by estrogen receptor (ER) status at P < 0.05. With the exception of rs2046210 at 6q25.1, the seven other SNPs showed a stronger association with ER-positive than ER-negative cancer. This study replicated all five genetic risk variants initially identified in Asians and provided evidence for associations of breast cancer risk in the East Asian population with nearly half of the genetic risk variants initially reported in GWASs conducted in European descendants. Taken together, these common genetic risk variants explain ∼10% of excess familial risk of breast cancer in Asian populations.

العلاقة: Zheng, W., Zhang, B., Cai, Q., Sung, H., Michailidou, K., Shi, J., Choi, J.-Y., Long, J., Dennis, J., Humphreys, M. K. et al. (2013) Common genetic determinants of breast-cancer risk in East Asian women : a collaborative study of 23 637 breast cancer cases and 25 579 controls. Human Molecular Genetics, Volume 22 (Number 12). pp. 2539-2550. doi:10.1093/hmg/ddt089

الإتاحة: https://doi.org/10.1093/hmg/ddt089Test
http://wrap.warwick.ac.uk/57611Test/