Please use this identifier to cite or link to this item: https://doi.org/10.1038/ng.2566
Title: Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer
Authors: Bojesen, S.E.
Pooley, K.A.
Johnatty, S.E.
Beesley, J.
Michailidou, K.
Tyrer, J.P.
Edwards, S.L.
Pickett, H.A.
Shen, H.C.
Smart, C.E.
Hillman, K.M.
Mai, P.L.
Lawrenson, K.
Stutz, M.D.
Lu, Y.
Karevan, R.
Woods, N.
Johnston, R.L.
French, J.D.
Chen, X.
Weischer, M.
Nielsen, S.F.
Maranian, M.J.
Ghoussaini, M.
Ahmed, S.
Baynes, C.
Bolla, M.K.
Wang, Q.
Dennis, J.
McGuffog, L.
Barrowdale, D.
Lee, A.
Healey, S.
Lush, M.
Tessier, D.C.
Vincent, D.
Bacot, F.
Vergote, I.
Lambrechts, S.
Despierre, E.
Risch, H.A.
González-Neira, A.
Rossing, M.A.
Pita, G.
Doherty, J.A.
Álvarez, N.
Larson, M.C.
Fridley, B.L.
Schoof, N.
Chang-Claude, J.
Cicek, M.S.
Peto, J.
Kalli, K.R.
Broeks, A.
Armasu, S.M.
Schmidt, M.K.
Braaf, L.M.
Winterhoff, B.
Nevanlinna, H.
Konecny, G.E.
Lambrechts, D.
Rogmann, L.
Guénel, P.
Teoman, A.
Milne, R.L.
Garcia, J.J.
Cox, A.
Shridhar, V.
Burwinkel, B.
Marme, F.
Hein, R.
Sawyer, E.J.
Haiman, C.A.
Wang-Gohrke, S.
Andrulis, I.L.
Moysich, K.B.
Hopper, J.L.
Odunsi, K.
Lindblom, A.
Giles, G.G.
Brenner, H.
Simard, J.
Lurie, G.
Fasching, P.A.
Carney, M.E.
Radice, P.
Wilkens, L.R.
Swerdlow, A.
Goodman, M.T.
Brauch, H.
Garcia-Closas, M.
Hillemanns, P.
Winqvist, R.
Dürst, M.
Devilee, P.
Runnebaum, I.
Jakubowska, A.
Lubinski, J.
Mannermaa, A.
Butzow, R.
Bogdanova, N.V.
Dörk, T.
Pelttari, L.M.
Zheng, W.
Leminen, A.
Anton-Culver, H.
Bunker, C.H.
Kristensen, V.
Ness, R.B.
Muir, K.
Edwards, R.
Meindl, A.
Heitz, F.
Matsuo, K.
Du Bois, A.
Wu, A.H.
Harter, P.
Teo, S.-H.
Schwaab, I.
Shu, X.-O.
Blot, W.
Hosono, S.
Kang, D.
Nakanishi, T.
Hartman, M. 
Yatabe, Y.
Hamann, U.
Karlan, B.Y.
Sangrajrang, S.
Kjaer, S.K.
Gaborieau, V.
Jensen, A.
Eccles, D.
Høgdall, E.
Shen, C.-Y.
Brown, J.
Woo, Y.L.
Shah, M.
Azmi, M.A.N.
Luben, R.
Omar, S.Z.
Czene, K.
Vierkant, R.A.
Nordestgaard, Bø.G.
Flyger, H.
Vachon, C.
Olson, J.E.
Wang, X.
Levine, D.A.
Rudolph, A.
Weber, R.P.
Flesch-Janys, D.
Iversen, E.
Nickels, S.
Schildkraut, J.M.
Silva, I.D.S.
Cramer, D.W.
Gibson, L.
Terry, K.L.
Fletcher, O.
Vitonis, A.F.
Van Der Schoot, C.E.
Poole, E.M.
Hogervorst, F.B.L.
Tworoger, S.S.
Liu, J.
Bandera, E.V.
Li, J.
Olson, S.H.
Humphreys, K.
Orlow, I.
Blomqvist, C.
Rodriguez-Rodriguez, L.
Aittomäki, K.
Salvesen, H.B.
Muranen, T.A.
Wik, E.
Brouwers, B.
Krakstad, C.
Wauters, E.
Halle, M.K.
Wildiers, H.
Kiemeney, L.A.
Mulot, C.
Aben, K.K.
Laurent-Puig, P.
Altena, A.M.
Truong, T.
Massuger, L.F.A.G.
Benitez, J.
Pejovic, T.
Perez, J.I.A.
Hoatlin, M.
Zamora, M.P.
Cook, L.S.
Balasubramanian, S.P.
Kelemen, L.E.
Schneeweiss, A.
Le, N.D.
Sohn, C.
Brooks-Wilson, A.
Tomlinson, I.
Kerin, M.J.
Miller, N.
Cybulski, C.
Henderson, B.E.
Menkiszak, J.
Schumacher, F.
Wentzensen, N.
Le Marchand, L.
Yang, H.P.
Mulligan, A.M.
Glendon, G.
Engelholm, S.A.
Knight, J.A.
Høgdall, C.K.
Apicella, C.
Gore, M.
Tsimiklis, H.
Song, H.
Southey, M.C.
Jager, A.
Den Ouweland, A.M.W.
Brown, R.
Martens, J.W.M.
Flanagan, J.M.
Kriege, M.
Paul, J.
Margolin, S.
Siddiqui, N.
Severi, G.
Whittemore, A.S.
Baglietto, L.
McGuire, V.
Stegmaier, C.
Sieh, W.
Müller, H.
Arndt, V.
Labrèche, F.
Gao, Y.-T.
Goldberg, M.S.
Yang, G.
Dumont, M.
McLaughlin, J.R.
Hartmann, A.
Ekici, A.B.
Beckmann, M.W.
Phelan, C.M.
Lux, M.P.
Permuth-Wey, J.
Peissel, B.
Sellers, T.A.
Ficarazzi, F.
Barile, M.
Ziogas, A.
Ashworth, A.
Gentry-Maharaj, A.
Jones, M.
Ramus, S.J.
Orr, N.
Menon, U.
Pearce, C.L.
Brüning, T.
Pike, M.C.
Ko, Y.-D.
Lissowska, J.
Figueroa, J.
Kupryjanczyk, J.
Chanock, S.J.
Dansonka-Mieszkowska, A.
Jukkola-Vuorinen, A.
Rzepecka, I.K.
Pylkäs, K.
Bidzinski, M.
Kauppila, S.
Hollestelle, A.
Seynaeve, C.
Tollenaar, R.A.E.M.
Durda, K.
Jaworska, K.
Hartikainen, J.M.
Kosma, V.-M.
Kataja, V.
Antonenkova, N.N.
Long, J.
Shrubsole, M.
Deming-Halverson, S.
Lophatananon, A.
Siriwanarangsan, P.
Stewart-Brown, S.
Ditsch, N.
Lichtner, P.
Schmutzler, R.K.
Ito, H.
Iwata, H.
Tajima, K.
Tseng, C.-C.
Stram, D.O.
Van Den Berg, D.
Yip, C.H.
Ikram, M.K.
Teh, Y.-C.
Cai, H.
Lu, W.
Signorello, L.B.
Cai, Q.
Noh, D.-Y.
Yoo, K.-Y.
Miao, H. 
Iau, P.T.-C.
Teo, Y.Y. 
McKay, J.
Shapiro, C.
Ademuyiwa, F.
Fountzilas, G.
Hsiung, C.-N.
Yu, J.-C.
Hou, M.-F.
Healey, C.S.
Luccarini, C.
Peock, S.
Stoppa-Lyonnet, D.
Peterlongo, P.
Rebbeck, T.R.
Piedmonte, M.
Singer, C.F.
Friedman, E.
Thomassen, M.
Offit, K.
Hansen, T.V.O.
Neuhausen, S.L.
Szabo, C.I.
Blanco, I.
Garber, J.
Narod, S.A.
Weitzel, J.N.
Montagna, M.
Olah, E.
Godwin, A.K.
Yannoukakos, D.
Goldgar, D.E.
Caldes, T.
Imyanitov, E.N.
Tihomirova, L.
Arun, B.K.
Campbell, I.
Mensenkamp, A.R.
Van Asperen, C.J.
Van Roozendaal, K.E.P.
Meijers-Heijboer, H.
Collée, J.M.
Oosterwijk, J.C.
Hooning, M.J.
Rookus, M.A.
Van Der Luijt, R.B.
Os, T.A.M.
Evans, D.G.
Frost, D.
Fineberg, E.
Barwell, J.
Walker, L.
Kennedy, M.J.
Platte, R.
Davidson, R.
Ellis, S.D.
Cole, T.
Bressac-De Paillerets, B.
Buecher, B.
Damiola, F.
Faivre, L.
Frenay, M.
Sinilnikova, O.M.
Caron, O.
Giraud, S.
Mazoyer, S.
Bonadona, V.
Caux-Moncoutier, V.
Toloczko-Grabarek, A.
Gronwald, J.
Byrski, T.
Spurdle, A.B.
Bonanni, B.
Zaffaroni, D.
Giannini, G.
Bernard, L.
Dolcetti, R.
Manoukian, S.
Arnold, N.
Engel, C.
Deissler, H.
Rhiem, K.
Niederacher, D.
Plendl, H.
Sutter, C.
Wappenschmidt, B.
Borg, Å.
Melin, B.
Rantala, J.
Soller, M.
Nathanson, K.L.
Domchek, S.M.
Rodriguez, G.C.
Salani, R.
Kaulich, D.G.
Tea, M.-K.
Paluch, S.S.
Laitman, Y.
Skytte, A.-B.
Kruse, T.A.
Jensen, U.B.
Robson, M.
Gerdes, A.-M.
Ejlertsen, B.
Foretova, L.
Savage, S.A.
Lester, J.
Soucy, P.
Kuchenbaecker, K.B.
Olswold, C.
Cunningham, J.M.
Slager, S.
Pankratz, V.S.
Dicks, E.
Lakhani, S.R.
Couch, F.J.
Hall, P.
Monteiro, A.N.A.
Gayther, S.A.
Pharoah, P.D.P.
Reddel, R.R.
Goode, E.L.
Greene, M.H.
Easton, D.F.
Berchuck, A.
Antoniou, A.C.
Chenevix-Trench, G.
Dunning, A.M.
Issue Date: Apr-2013
Source: Bojesen, S.E., Pooley, K.A., Johnatty, S.E., Beesley, J., Michailidou, K., Tyrer, J.P., Edwards, S.L., Pickett, H.A., Shen, H.C., Smart, C.E., Hillman, K.M., Mai, P.L., Lawrenson, K., Stutz, M.D., Lu, Y., Karevan, R., Woods, N., Johnston, R.L., French, J.D., Chen, X., Weischer, M., Nielsen, S.F., Maranian, M.J., Ghoussaini, M., Ahmed, S., Baynes, C., Bolla, M.K., Wang, Q., Dennis, J., McGuffog, L., Barrowdale, D., Lee, A., Healey, S., Lush, M., Tessier, D.C., Vincent, D., Bacot, F., Vergote, I., Lambrechts, S., Despierre, E., Risch, H.A., González-Neira, A., Rossing, M.A., Pita, G., Doherty, J.A., Álvarez, N., Larson, M.C., Fridley, B.L., Schoof, N., Chang-Claude, J., Cicek, M.S., Peto, J., Kalli, K.R., Broeks, A., Armasu, S.M., Schmidt, M.K., Braaf, L.M., Winterhoff, B., Nevanlinna, H., Konecny, G.E., Lambrechts, D., Rogmann, L., Guénel, P., Teoman, A., Milne, R.L., Garcia, J.J., Cox, A., Shridhar, V., Burwinkel, B., Marme, F., Hein, R., Sawyer, E.J., Haiman, C.A., Wang-Gohrke, S., Andrulis, I.L., Moysich, K.B., Hopper, J.L., Odunsi, K., Lindblom, A., Giles, G.G., Brenner, H., Simard, J., Lurie, G., Fasching, P.A., Carney, M.E., Radice, P., Wilkens, L.R., Swerdlow, A., Goodman, M.T., Brauch, H., Garcia-Closas, M., Hillemanns, P., Winqvist, R., Dürst, M., Devilee, P., Runnebaum, I., Jakubowska, A., Lubinski, J., Mannermaa, A., Butzow, R., Bogdanova, N.V., Dörk, T., Pelttari, L.M., Zheng, W., Leminen, A., Anton-Culver, H., Bunker, C.H., Kristensen, V., Ness, R.B., Muir, K., Edwards, R., Meindl, A., Heitz, F., Matsuo, K., Du Bois, A., Wu, A.H., Harter, P., Teo, S.-H., Schwaab, I., Shu, X.-O., Blot, W., Hosono, S., Kang, D., Nakanishi, T., Hartman, M., Yatabe, Y., Hamann, U., Karlan, B.Y., Sangrajrang, S., Kjaer, S.K., Gaborieau, V., Jensen, A., Eccles, D., Høgdall, E., Shen, C.-Y., Brown, J., Woo, Y.L., Shah, M., Azmi, M.A.N., Luben, R., Omar, S.Z., Czene, K., Vierkant, R.A., Nordestgaard, Bø.G., Flyger, H., Vachon, C., Olson, J.E., Wang, X., Levine, D.A., Rudolph, A., Weber, R.P., Flesch-Janys, D., Iversen, E., Nickels, S., Schildkraut, J.M., Silva, I.D.S., Cramer, D.W., Gibson, L., Terry, K.L., Fletcher, O., Vitonis, A.F., Van Der Schoot, C.E., Poole, E.M., Hogervorst, F.B.L., Tworoger, S.S., Liu, J., Bandera, E.V., Li, J., Olson, S.H., Humphreys, K., Orlow, I., Blomqvist, C., Rodriguez-Rodriguez, L., Aittomäki, K., Salvesen, H.B., Muranen, T.A., Wik, E., Brouwers, B., Krakstad, C., Wauters, E., Halle, M.K., Wildiers, H., Kiemeney, L.A., Mulot, C., Aben, K.K., Laurent-Puig, P., Altena, A.M., Truong, T., Massuger, L.F.A.G., Benitez, J., Pejovic, T., Perez, J.I.A., Hoatlin, M., Zamora, M.P., Cook, L.S., Balasubramanian, S.P., Kelemen, L.E., Schneeweiss, A., Le, N.D., Sohn, C., Brooks-Wilson, A., Tomlinson, I., Kerin, M.J., Miller, N., Cybulski, C., Henderson, B.E., Menkiszak, J., Schumacher, F., Wentzensen, N., Le Marchand, L., Yang, H.P., Mulligan, A.M., Glendon, G., Engelholm, S.A., Knight, J.A., Høgdall, C.K., Apicella, C., Gore, M., Tsimiklis, H., Song, H., Southey, M.C., Jager, A., Den Ouweland, A.M.W., Brown, R., Martens, J.W.M., Flanagan, J.M., Kriege, M., Paul, J., Margolin, S., Siddiqui, N., Severi, G., Whittemore, A.S., Baglietto, L., McGuire, V., Stegmaier, C., Sieh, W., Müller, H., Arndt, V., Labrèche, F., Gao, Y.-T., Goldberg, M.S., Yang, G., Dumont, M., McLaughlin, J.R., Hartmann, A., Ekici, A.B., Beckmann, M.W., Phelan, C.M., Lux, M.P., Permuth-Wey, J., Peissel, B., Sellers, T.A., Ficarazzi, F., Barile, M., Ziogas, A., Ashworth, A., Gentry-Maharaj, A., Jones, M., Ramus, S.J., Orr, N., Menon, U., Pearce, C.L., Brüning, T., Pike, M.C., Ko, Y.-D., Lissowska, J., Figueroa, J., Kupryjanczyk, J., Chanock, S.J., Dansonka-Mieszkowska, A., Jukkola-Vuorinen, A., Rzepecka, I.K., Pylkäs, K., Bidzinski, M., Kauppila, S., Hollestelle, A., Seynaeve, C., Tollenaar, R.A.E.M., Durda, K., Jaworska, K., Hartikainen, J.M., Kosma, V.-M., Kataja, V., Antonenkova, N.N., Long, J., Shrubsole, M., Deming-Halverson, S., Lophatananon, A., Siriwanarangsan, P., Stewart-Brown, S., Ditsch, N., Lichtner, P., Schmutzler, R.K., Ito, H., Iwata, H., Tajima, K., Tseng, C.-C., Stram, D.O., Van Den Berg, D., Yip, C.H., Ikram, M.K., Teh, Y.-C., Cai, H., Lu, W., Signorello, L.B., Cai, Q., Noh, D.-Y., Yoo, K.-Y., Miao, H., Iau, P.T.-C., Teo, Y.Y., McKay, J., Shapiro, C., Ademuyiwa, F., Fountzilas, G., Hsiung, C.-N., Yu, J.-C., Hou, M.-F., Healey, C.S., Luccarini, C., Peock, S., Stoppa-Lyonnet, D., Peterlongo, P., Rebbeck, T.R., Piedmonte, M., Singer, C.F., Friedman, E., Thomassen, M., Offit, K., Hansen, T.V.O., Neuhausen, S.L., Szabo, C.I., Blanco, I., Garber, J., Narod, S.A., Weitzel, J.N., Montagna, M., Olah, E., Godwin, A.K., Yannoukakos, D., Goldgar, D.E., Caldes, T., Imyanitov, E.N., Tihomirova, L., Arun, B.K., Campbell, I., Mensenkamp, A.R., Van Asperen, C.J., Van Roozendaal, K.E.P., Meijers-Heijboer, H., Collée, J.M., Oosterwijk, J.C., Hooning, M.J., Rookus, M.A., Van Der Luijt, R.B., Os, T.A.M., Evans, D.G., Frost, D., Fineberg, E., Barwell, J., Walker, L., Kennedy, M.J., Platte, R., Davidson, R., Ellis, S.D., Cole, T., Bressac-De Paillerets, B., Buecher, B., Damiola, F., Faivre, L., Frenay, M., Sinilnikova, O.M., Caron, O., Giraud, S., Mazoyer, S., Bonadona, V., Caux-Moncoutier, V., Toloczko-Grabarek, A., Gronwald, J., Byrski, T., Spurdle, A.B., Bonanni, B., Zaffaroni, D., Giannini, G., Bernard, L., Dolcetti, R., Manoukian, S., Arnold, N., Engel, C., Deissler, H., Rhiem, K., Niederacher, D., Plendl, H., Sutter, C., Wappenschmidt, B., Borg, Å., Melin, B., Rantala, J., Soller, M., Nathanson, K.L., Domchek, S.M., Rodriguez, G.C., Salani, R., Kaulich, D.G., Tea, M.-K., Paluch, S.S., Laitman, Y., Skytte, A.-B., Kruse, T.A., Jensen, U.B., Robson, M., Gerdes, A.-M., Ejlertsen, B., Foretova, L., Savage, S.A., Lester, J., Soucy, P., Kuchenbaecker, K.B., Olswold, C., Cunningham, J.M., Slager, S., Pankratz, V.S., Dicks, E., Lakhani, S.R., Couch, F.J., Hall, P., Monteiro, A.N.A., Gayther, S.A., Pharoah, P.D.P., Reddel, R.R., Goode, E.L., Greene, M.H., Easton, D.F., Berchuck, A., Antoniou, A.C., Chenevix-Trench, G., Dunning, A.M. (2013-04). Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer. Nature Genetics 45 (4) : 371-384. ScholarBank@NUS Repository. https://doi.org/10.1038/ng.2566
Abstract: TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOGs, we analyzed ∼480 SNPs at the TERT locus in breast (n = 103,991), ovarian (n = 39,774) and BRCA1 mutation carrier (n = 11,705) cancer cases and controls. Leukocyte telomere measurements were also available for 53,724 participants. Most associations cluster into three independent peaks. The minor allele at the peak 1 SNP rs2736108 associates with longer telomeres (P = 5.8 × 10 -7), lower risks for estrogen receptor (ER)-negative (P = 1.0 × 10 -8) and BRCA1 mutation carrier (P = 1.1 × 10 -5) breast cancers and altered promoter assay signal. The minor allele at the peak 2 SNP rs7705526 associates with longer telomeres (P = 2.3 × 10 -14), higher risk of low-malignant-potential ovarian cancer (P = 1.3 × 10 -15) and greater promoter activity. The minor alleles at the peak 3 SNPs rs10069690 and rs2242652 increase ER-negative (P = 1.2 × 10 -12) and BRCA1 mutation carrier (P = 1.6 × 10 -14) breast and invasive ovarian (P = 1.3 × 10 -11) cancer risks but not via altered telomere length. The cancer risk alleles of rs2242652 and rs10069690, respectively, increase silencing and generate a truncated TERT splice variant.
Source Title: Nature Genetics
URI: http://scholarbank.nus.edu.sg/handle/10635/108995
ISSN: 10614036
DOI: 10.1038/ng.2566
Appears in Collections:Staff Publications

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