Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer

SE Bojesen; YC Teh; KA Pooley; SE Johnatty; J Beesley; K Michailidou; JP Tyrer; SL Edwards; HA Pickett; HC Shen; CE Smart; KM Hillman; PL Mai; K Lawrenson; MD Stutz; Y Lu; R Karevan; N Woods; RL Johnstonw; JD French; XQ Chen; M Weischer; SF Nielsen; MJ Maranian; M Ghoussaini; S (Shahana) Ahmed; C Baynes; MK Bolla; Q (Qing) Wang; J Dennis; L McGuffog; D Barrowdale; A van der Lee; S Healey; M Lush; DC Tessier; D Vincent; F Bacot; I Vergote; S Lambrechts; E Despierre; HA Risch; A Gonzaalez-Neira; MA Rossing; G Pita; JA Doherty; N Alvarez; MC Larson; BL Fridley; N Schoof; J Chang-Claude; MS Cicek; J Peto; KR Kalli; A Broeks; SM Armasu; Marjanka K Schmidt; LM Braaf; B Winterhoff; H Nevanlinna; GE Konecny; D Lambrechts; L Rogmann; P Guenel; A Teoman; RL Milne; JJ Garcia; A Cox; V Shridhar; B Burwinkel; F Marme; R Hein; EJ Sawyer; CA Haiman; S Wang-Gohrke; IL Andrulis; KB Moysich; JL Hopper; K Odunsi; A Lindblom; GG Giles; H Brenner; J Simard; G Lurie; PA Fasching; ME Carney; P Radice; LR Wilkens; A Swerdlow; MT Goodman; H Brauch; M Garcia-Closas; P Hillemanns; R Winqvist; M Durst; P Devilee; I Runnebaum; A Jakubowska; J Lubinski; A Mannermaa; R Butzow; NV Bogdanova; T Dork; LM Pelttari; W Zheng; A Leminen; H Anton-Culver; CH Bunker; V Kristensen; RB Ness; K Muir; R Edwards; A Meind; F Heitz; K Matsuo; A du Blois; AH Wu; P Harter; SH Teo; I Schwaab; XO Shu; W Blot; S Hosono; D Kang; T Nakanishi; M Hartman; Y Yatabe; U Hamann; BY Karlan; S Sangrajrang; SK Kjaer; V Gaborieau; A Jensen; D Eccles; E Hogdall; CY Shen; J Brown; YL Woo; M Shah; MAN Azmi; R Luben; SZ Omar; K Czene; RA Vierkant; BG Nordestgaard; H Flyger; C Vachon; JE Olson; XS Wang; DA Levine; A Rudolph; RP Weber; D Flesch-Janys; E Iversen; S Nickels; JM Schildkraut; ID Silva; DW Cramer; L Gibson; KL Terry; O Fletcher; AF Vitonis; CE van der Schoot; EM Poole; FBL Hogervorst; SS Tworoger; JJ Liu; EV Bandera; JM Li; SH Olson; K Humphreys; I Row; C Blomqvist; L Rodriguez-Rodriguez; K Aittomaki; HB Salvesen; TA Muranen; E Wik; B Brouwers; C Krakstad; Erwin Wauters; MK Halle; H Wildiers; LA Kiemeney; C Mulot; KK Aben; P Laurent-Puig; AM van Altena; T Truong; LFAG Massuger; J Benitez; T Pejovic; JIA Perez; M Hoatlin; MP Zamora; LS Cook; SP Balasubramanian; LE Kelemen; A Schneeweiss; ND Le; C Sohn; A Brooks-Wilson; I Tomlinson; MJ Kerin; N Miller; C Cybulski; BE Henderson; J Menkiszak; FR Schumacher; N Wentzensen; L Le Marchand; HP (Hannah) Yang; AM Mulligan; G Glendon; SA Engelholm; JA Knight; CK Hogdall; C Apicella; M Gore; H Tsimiklis; HL Song; MC Southey; Agnes Jager; Ans van den Ouweland; R Brown; John Martens; JM Flanagan; Mieke Kriege; J Paul; S Margolin; N Siddiqui; G Severi; AS Whittemore; L Baglietto; V McGuire; C Stegmaier; W Sieh; H Muller; V Arndt; F Labreche; YT Gao; MS Goldberg; M Dumont; JR McLaughlin; A Hartmann; AB Ekici; MW Beckmann; CM Phelan; MP Lux; J Permuth-Wey; B Peissel; TA Sellers; F Ficarazzi; M Barile; A Ziogas; A Ashworth; A Gentry-Maharaj; M Jones; SJ Ramus; N Orr; U Menon; CL Pearce; T Bruning; MC Pike; YD Ko; J Lissowska; J Figueroa; J Kupryjanczyk; SJ Chanock; A Dansonka-Mieszkowska; A Jukkola-Vuorinen; IK Rzepecka; K Pylkas; M Bidzinski; S Kauppila; Antoinette Hollestelle; Caroline Seynaeve; RAEM Tollenaar; K Durda; K Jaworska; JM Hartikainen; VM Kosma; V Kataja; NN Antonenkova; JR Long; M Shrubsole; S Deming-Halverson; A Lophatananon; P Siriwanarangsan; S Stewart-Brown; N Ditsch; P Lichtner; RK Schmutzler; H Ito; H Iwata; K Tajima; CC Tseng; DO Stram; D van den Berg; CH Yip; MK Ikrarn; H Cai; W Lu; LB Signorello; QY Cai; DY Noh; KY Yoo; H Miao; PTC Iau; YY Teo; J Mckay; C Shapiro; F Ademuyiwa; G Fountzilas; CN Hsiung; JC Yu; MF Hou; CS Healey; C Luccarini; S Peock; D Stoppa-Lyonnet; P Peterlongo; TR Rebbeck; M Piedmonte; CF Singer; E Friedman; Marga Thomassen; K Offit; TVO Hansen; SL Neuhausen; CI Szabo; I Blanco; J Garber; SA Narod; JN Weitzel; M Montagna; E Olah; AK Godwin; D Yannoukakos; DE Goldgar; T Caldes; EN Imyanitov; L Tihomirova; BK Arun; I Campbell; AR Mensenkamp; CJ van Asperen; KEP van Roozendaa; H Meijers-Heijboer; Margriet Collee; JC Oosterwijk; Maartje Hooning; MA Rookus; RB van der Luijt; TAM van Os; DG Evans; D Frost; E Fineberg; J Barwell; L Walker; MJ Kennedy; R Platte; R Davidson; SD Ellis; T Cole; B Bressac-de Paillerets; B Buecher; F Damiola; L Faivre; M Frenay; OM Sinilnikova; O (Olivier) Caron; S Giraud; S Mazoyer; V Bonadona; V Caux-Moncoutier; A Toloczko-Grabarek; J Gronwald; T Byrski; AB Spurdle; B Bonanni; D Zaffaroni; G Giannini; L Bernard; R Dolcetti; S Manoukian; N Arnold; C Engel; H Deissler; K Rhiem; D Niederacher; H Pendl; C Sutter; B Wappenschmidt; A Borg; B Mein; J Rantala; M Soller; KL Nathanson; SM Domchek; GC Rodriguez; R Salani; DG Kaulich; MK Tea; SS Paluch; Y Laitman; AB Skytte; TA Kruse; UB Jensen; M Robson; AM Gerdes; B Ejlertsen; L Foretova; SA Savage; J Lesterm; P Soucy; KB Kuchenbaecker; C Olswold; JM Cunningham; S Slager; VS Pankratz; E Dicks; SR Lakhani; FJ Couch; P Hall; ANA Monteiro; SA Gayther; PDP Pharoah; RR Reddel; EL Goode; MH Greene; DF Easton; A Berchuck; AC Antoniou; G Chenevix-Trench; AM Dunning

doi:10.1038/ng.2566

Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer

SE Bojesen, YC Teh, KA Pooley, SE Johnatty, J Beesley, K Michailidou, JP Tyrer, SL Edwards, HA Pickett, HC Shen, CE Smart, KM Hillman, PL Mai, K Lawrenson, MD Stutz, Y Lu, R Karevan, N Woods, RL Johnstonw, JD FrenchXQ Chen, M Weischer, SF Nielsen, MJ Maranian, M Ghoussaini, S (Shahana) Ahmed, C Baynes, MK Bolla, Q (Qing) Wang, J Dennis, L McGuffog, D Barrowdale, A van der Lee, S Healey, M Lush, DC Tessier, D Vincent, F Bacot, I Vergote, S Lambrechts, E Despierre, HA Risch, A Gonzaalez-Neira, MA Rossing, G Pita, JA Doherty, N Alvarez, MC Larson, BL Fridley, N Schoof, J Chang-Claude, MS Cicek, J Peto, KR Kalli, A Broeks, SM Armasu, Marjanka K Schmidt, LM Braaf, B Winterhoff, H Nevanlinna, GE Konecny, D Lambrechts, L Rogmann, P Guenel, A Teoman, RL Milne, JJ Garcia, A Cox, V Shridhar, B Burwinkel, F Marme, R Hein, EJ Sawyer, CA Haiman, S Wang-Gohrke, IL Andrulis, KB Moysich, JL Hopper, K Odunsi, A Lindblom, GG Giles, H Brenner, J Simard, G Lurie, PA Fasching, ME Carney, P Radice, LR Wilkens, A Swerdlow, MT Goodman, H Brauch, M Garcia-Closas, P Hillemanns, R Winqvist, M Durst, P Devilee, I Runnebaum, A Jakubowska, J Lubinski, A Mannermaa, R Butzow, NV Bogdanova, T Dork, LM Pelttari, W Zheng, A Leminen, H Anton-Culver, CH Bunker, V Kristensen, RB Ness, K Muir, R Edwards, A Meind, F Heitz, K Matsuo, A du Blois, AH Wu, P Harter, SH Teo, I Schwaab, XO Shu, W Blot, S Hosono, D Kang, T Nakanishi, M Hartman, Y Yatabe, U Hamann, BY Karlan, S Sangrajrang, SK Kjaer, V Gaborieau, A Jensen, D Eccles, E Hogdall, CY Shen, J Brown, YL Woo, M Shah, MAN Azmi, R Luben, SZ Omar, K Czene, RA Vierkant, BG Nordestgaard, H Flyger, C Vachon, JE Olson, XS Wang, DA Levine, A Rudolph, RP Weber, D Flesch-Janys, E Iversen, S Nickels, JM Schildkraut, ID Silva, DW Cramer, L Gibson, KL Terry, O Fletcher, AF Vitonis, CE van der Schoot, EM Poole, FBL Hogervorst, SS Tworoger, JJ Liu, EV Bandera, JM Li, SH Olson, K Humphreys, I Row, C Blomqvist, L Rodriguez-Rodriguez, K Aittomaki, HB Salvesen, TA Muranen, E Wik, B Brouwers, C Krakstad, Erwin Wauters, MK Halle, H Wildiers, LA Kiemeney, C Mulot, KK Aben, P Laurent-Puig, AM van Altena, T Truong, LFAG Massuger, J Benitez, T Pejovic, JIA Perez, M Hoatlin, MP Zamora, LS Cook, SP Balasubramanian, LE Kelemen, A Schneeweiss, ND Le, C Sohn, A Brooks-Wilson, I Tomlinson, MJ Kerin, N Miller, C Cybulski, BE Henderson, J Menkiszak, FR Schumacher, N Wentzensen, L Le Marchand, HP (Hannah) Yang, AM Mulligan, G Glendon, SA Engelholm, JA Knight, CK Hogdall, C Apicella, M Gore, H Tsimiklis, HL Song, MC Southey, Agnes Jager, Ans van den Ouweland, R Brown, John Martens, JM Flanagan, Mieke Kriege, J Paul, S Margolin, N Siddiqui, G Severi, AS Whittemore, L Baglietto, V McGuire, C Stegmaier, W Sieh, H Muller, V Arndt, F Labreche, YT Gao, MS Goldberg, M Dumont, JR McLaughlin, A Hartmann, AB Ekici, MW Beckmann, CM Phelan, MP Lux, J Permuth-Wey, B Peissel, TA Sellers, F Ficarazzi, M Barile, A Ziogas, A Ashworth, A Gentry-Maharaj, M Jones, SJ Ramus, N Orr, U Menon, CL Pearce, T Bruning, MC Pike, YD Ko, J Lissowska, J Figueroa, J Kupryjanczyk, SJ Chanock, A Dansonka-Mieszkowska, A Jukkola-Vuorinen, IK Rzepecka, K Pylkas, M Bidzinski, S Kauppila, Antoinette Hollestelle, Caroline Seynaeve, RAEM Tollenaar, K Durda, K Jaworska, JM Hartikainen, VM Kosma, V Kataja, NN Antonenkova, JR Long, M Shrubsole, S Deming-Halverson, A Lophatananon, P Siriwanarangsan, S Stewart-Brown, N Ditsch, P Lichtner, RK Schmutzler, H Ito, H Iwata, K Tajima, CC Tseng, DO Stram, D van den Berg, CH Yip, MK Ikrarn, H Cai, W Lu, LB Signorello, QY Cai, DY Noh, KY Yoo, H Miao, PTC Iau, YY Teo, J Mckay, C Shapiro, F Ademuyiwa, G Fountzilas, CN Hsiung, JC Yu, MF Hou, CS Healey, C Luccarini, S Peock, D Stoppa-Lyonnet, P Peterlongo, TR Rebbeck, M Piedmonte, CF Singer, E Friedman, Marga Thomassen, K Offit, TVO Hansen, SL Neuhausen, CI Szabo, I Blanco, J Garber, SA Narod, JN Weitzel, M Montagna, E Olah, AK Godwin, D Yannoukakos, DE Goldgar, T Caldes, EN Imyanitov, L Tihomirova, BK Arun, I Campbell, AR Mensenkamp, CJ van Asperen, KEP van Roozendaa, H Meijers-Heijboer, Margriet Collee, JC Oosterwijk, Maartje Hooning, MA Rookus, RB van der Luijt, TAM van Os, DG Evans, D Frost, E Fineberg, J Barwell, L Walker, MJ Kennedy, R Platte, R Davidson, SD Ellis, T Cole, B Bressac-de Paillerets, B Buecher, F Damiola, L Faivre, M Frenay, OM Sinilnikova, O (Olivier) Caron, S Giraud, S Mazoyer, V Bonadona, V Caux-Moncoutier, A Toloczko-Grabarek, J Gronwald, T Byrski, AB Spurdle, B Bonanni, D Zaffaroni, G Giannini, L Bernard, R Dolcetti, S Manoukian, N Arnold, C Engel, H Deissler, K Rhiem, D Niederacher, H Pendl, C Sutter, B Wappenschmidt, A Borg, B Mein, J Rantala, M Soller, KL Nathanson, SM Domchek, GC Rodriguez, R Salani, DG Kaulich, MK Tea, SS Paluch, Y Laitman, AB Skytte, TA Kruse, UB Jensen, M Robson, AM Gerdes, B Ejlertsen, L Foretova, SA Savage, J Lesterm, P Soucy, KB Kuchenbaecker, C Olswold, JM Cunningham, S Slager, VS Pankratz, E Dicks, SR Lakhani, FJ Couch, P Hall, ANA Monteiro, SA Gayther, PDP Pharoah, RR Reddel, EL Goode, MH Greene, DF Easton, A Berchuck, AC Antoniou, G Chenevix-Trench, AM Dunning

Research output: Contribution to journal › Article › Academic › peer-review

467 Citations (Scopus)

Abstract

TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOG, we analyzed similar to 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 x 10(-7)), lower risks for estrogen receptor (ER)-negative (P = 1.0 x 10(-8)) and BRCA1 mutation carrier (P = 1.1 x 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 x 10(-14)), higher risk of low-malignant-potential ovarian cancer (P = 1.3 x 10(-15)) and greater promoter activity. The minor alleles at the peak 3 SNPs rs10069690 and rs2242652 increase ER-negative (P = 1.2 x 10(-12)) and BRCA1 mutation carrier (P = 1.6 x 10-14) breast and invasive ovarian (P = 1.3 x 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.

Original language	English
Pages (from-to)	371-384
Number of pages	14
Journal	Nature Genetics
Volume	45
Issue number	4
DOIs	https://doi.org/10.1038/ng.2566
Publication status	Published - 2013

Research programs

EMC MGC-02-96-01
EMC MM-03-86-01

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/ng.2566

http://hdl.handle.net/1765/58862

Cite this

Bojesen, SE., Teh, YC., Pooley, KA., Johnatty, SE., Beesley, J., Michailidou, K., Tyrer, JP., Edwards, SL., Pickett, HA., Shen, HC., Smart, CE., Hillman, KM., Mai, PL., Lawrenson, K., Stutz, MD., Lu, Y., Karevan, R., Woods, N., Johnstonw, RL., ... Dunning, AM. (2013). 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. https://doi.org/10.1038/ng.2566

@article{9168457826874f98910170acaabe3db2,

title = "Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer",

abstract = "TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOG, we analyzed similar to 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 x 10(-7)), lower risks for estrogen receptor (ER)-negative (P = 1.0 x 10(-8)) and BRCA1 mutation carrier (P = 1.1 x 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 x 10(-14)), higher risk of low-malignant-potential ovarian cancer (P = 1.3 x 10(-15)) and greater promoter activity. The minor alleles at the peak 3 SNPs rs10069690 and rs2242652 increase ER-negative (P = 1.2 x 10(-12)) and BRCA1 mutation carrier (P = 1.6 x 10-14) breast and invasive ovarian (P = 1.3 x 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.",

author = "SE Bojesen and YC Teh and KA Pooley and SE Johnatty and J Beesley and K Michailidou and JP Tyrer and SL Edwards and HA Pickett and HC Shen and CE Smart and KM Hillman and PL Mai and K Lawrenson and MD Stutz and Y Lu and R Karevan and N Woods and RL Johnstonw and JD French and XQ Chen and M Weischer and SF Nielsen and MJ Maranian and M Ghoussaini and Ahmed, {S (Shahana)} and C Baynes and MK Bolla and Wang, {Q (Qing)} and J Dennis and L McGuffog and D Barrowdale and {van der Lee}, A and S Healey and M Lush and DC Tessier and D Vincent and F Bacot and I Vergote and S Lambrechts and E Despierre and HA Risch and A Gonzaalez-Neira and MA Rossing and G Pita and JA Doherty and N Alvarez and MC Larson and BL Fridley and N Schoof and J Chang-Claude and MS Cicek and J Peto and KR Kalli and A Broeks and SM Armasu and Schmidt, {Marjanka K} and LM Braaf and B Winterhoff and H Nevanlinna and GE Konecny and D Lambrechts and L Rogmann and P Guenel and A Teoman and RL Milne and JJ Garcia and A Cox and V Shridhar and B Burwinkel and F Marme and R Hein and EJ Sawyer and CA Haiman and S Wang-Gohrke and IL Andrulis and KB Moysich and JL Hopper and K Odunsi and A Lindblom and GG Giles and H Brenner and J Simard and G Lurie and PA Fasching and ME Carney and P Radice and LR Wilkens and A Swerdlow and MT Goodman and H Brauch and M Garcia-Closas and P Hillemanns and R Winqvist and M Durst and P Devilee and I Runnebaum and A Jakubowska and J Lubinski and A Mannermaa and R Butzow and NV Bogdanova and T Dork and LM Pelttari and W Zheng and A Leminen and H Anton-Culver and CH Bunker and V Kristensen and RB Ness and K Muir and R Edwards and A Meind and F Heitz and K Matsuo and {du Blois}, A and AH Wu and P Harter and SH Teo and I Schwaab and XO Shu and W Blot and S Hosono and D Kang and T Nakanishi and M Hartman and Y Yatabe and U Hamann and BY Karlan and S Sangrajrang and SK Kjaer and V Gaborieau and A Jensen and D Eccles and E Hogdall and CY Shen and J Brown and YL Woo and M Shah and MAN Azmi and R Luben and SZ Omar and K Czene and RA Vierkant and BG Nordestgaard and H Flyger and C Vachon and JE Olson and XS Wang and DA Levine and A Rudolph and RP Weber and D Flesch-Janys and E Iversen and S Nickels and JM Schildkraut and ID Silva and DW Cramer and L Gibson and KL Terry and O Fletcher and AF Vitonis and {van der Schoot}, CE and EM Poole and FBL Hogervorst and SS Tworoger and JJ Liu and EV Bandera and JM Li and SH Olson and K Humphreys and I Row and C Blomqvist and L Rodriguez-Rodriguez and K Aittomaki and HB Salvesen and TA Muranen and E Wik and B Brouwers and C Krakstad and Erwin Wauters and MK Halle and H Wildiers and LA Kiemeney and C Mulot and KK Aben and P Laurent-Puig and {van Altena}, AM and T Truong and LFAG Massuger and J Benitez and T Pejovic and JIA Perez and M Hoatlin and MP Zamora and LS Cook and SP Balasubramanian and LE Kelemen and A Schneeweiss and ND Le and C Sohn and A Brooks-Wilson and I Tomlinson and MJ Kerin and N Miller and C Cybulski and BE Henderson and J Menkiszak and FR Schumacher and N Wentzensen and {Le Marchand}, L and Yang, {HP (Hannah)} and AM Mulligan and G Glendon and SA Engelholm and JA Knight and CK Hogdall and C Apicella and M Gore and H Tsimiklis and HL Song and MC Southey and Agnes Jager and {van den Ouweland}, Ans and R Brown and John Martens and JM Flanagan and Mieke Kriege and J Paul and S Margolin and N Siddiqui and G Severi and AS Whittemore and L Baglietto and V McGuire and C Stegmaier and W Sieh and H Muller and V Arndt and F Labreche and YT Gao and MS Goldberg and M Dumont and JR McLaughlin and A Hartmann and AB Ekici and MW Beckmann and CM Phelan and MP Lux and J Permuth-Wey and B Peissel and TA Sellers and F Ficarazzi and M Barile and A Ziogas and A Ashworth and A Gentry-Maharaj and M Jones and SJ Ramus and N Orr and U Menon and CL Pearce and T Bruning and MC Pike and YD Ko and J Lissowska and J Figueroa and J Kupryjanczyk and SJ Chanock and A Dansonka-Mieszkowska and A Jukkola-Vuorinen and IK Rzepecka and K Pylkas and M Bidzinski and S Kauppila and Antoinette Hollestelle and Caroline Seynaeve and RAEM Tollenaar and K Durda and K Jaworska and JM Hartikainen and VM Kosma and V Kataja and NN Antonenkova and JR Long and M Shrubsole and S Deming-Halverson and A Lophatananon and P Siriwanarangsan and S Stewart-Brown and N Ditsch and P Lichtner and RK Schmutzler and H Ito and H Iwata and K Tajima and CC Tseng and DO Stram and {van den Berg}, D and CH Yip and MK Ikrarn and H Cai and W Lu and LB Signorello and QY Cai and DY Noh and KY Yoo and H Miao and PTC Iau and YY Teo and J Mckay and C Shapiro and F Ademuyiwa and G Fountzilas and CN Hsiung and JC Yu and MF Hou and CS Healey and C Luccarini and S Peock and D Stoppa-Lyonnet and P Peterlongo and TR Rebbeck and M Piedmonte and CF Singer and E Friedman and Marga Thomassen and K Offit and TVO Hansen and SL Neuhausen and CI Szabo and I Blanco and J Garber and SA Narod and JN Weitzel and M Montagna and E Olah and AK Godwin and D Yannoukakos and DE Goldgar and T Caldes and EN Imyanitov and L Tihomirova and BK Arun and I Campbell and AR Mensenkamp and {van Asperen}, CJ and {van Roozendaa}, KEP and H Meijers-Heijboer and Margriet Collee and JC Oosterwijk and Maartje Hooning and MA Rookus and {van der Luijt}, RB and {van Os}, TAM and DG Evans and D Frost and E Fineberg and J Barwell and L Walker and MJ Kennedy and R Platte and R Davidson and SD Ellis and T Cole and {Bressac-de Paillerets}, B and B Buecher and F Damiola and L Faivre and M Frenay and OM Sinilnikova and Caron, {O (Olivier)} and S Giraud and S Mazoyer and V Bonadona and V Caux-Moncoutier and A Toloczko-Grabarek and J Gronwald and T Byrski and AB Spurdle and B Bonanni and D Zaffaroni and G Giannini and L Bernard and R Dolcetti and S Manoukian and N Arnold and C Engel and H Deissler and K Rhiem and D Niederacher and H Pendl and C Sutter and B Wappenschmidt and A Borg and B Mein and J Rantala and M Soller and KL Nathanson and SM Domchek and GC Rodriguez and R Salani and DG Kaulich and MK Tea and SS Paluch and Y Laitman and AB Skytte and TA Kruse and UB Jensen and M Robson and AM Gerdes and B Ejlertsen and L Foretova and SA Savage and J Lesterm and P Soucy and KB Kuchenbaecker and C Olswold and JM Cunningham and S Slager and VS Pankratz and E Dicks and SR Lakhani and FJ Couch and P Hall and ANA Monteiro and SA Gayther and PDP Pharoah and RR Reddel and EL Goode and MH Greene and DF Easton and A Berchuck and AC Antoniou and G Chenevix-Trench and AM Dunning",

year = "2013",

doi = "10.1038/ng.2566",

language = "English",

volume = "45",

pages = "371--384",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "4",

}

Bojesen, SE, Teh, YC, Pooley, KA, Johnatty, SE, Beesley, J, Michailidou, K, Tyrer, JP, Edwards, SL, Pickett, HA, Shen, HC, Smart, CE, Hillman, KM, Mai, PL, Lawrenson, K, Stutz, MD, Lu, Y, Karevan, R, Woods, N, Johnstonw, RL, French, JD, Chen, XQ, Weischer, M, Nielsen, SF, Maranian, MJ, Ghoussaini, M, Ahmed, S, Baynes, C, Bolla, MK, Wang, Q, Dennis, J, McGuffog, L, Barrowdale, D, van der Lee, A, Healey, S, Lush, M, Tessier, DC, Vincent, D, Bacot, F, Vergote, I, Lambrechts, S, Despierre, E, Risch, HA, Gonzaalez-Neira, A, Rossing, MA, Pita, G, Doherty, JA, Alvarez, N, Larson, MC, Fridley, BL, Schoof, N, Chang-Claude, J, Cicek, MS, Peto, J, Kalli, KR, Broeks, A, Armasu, SM, Schmidt, MK, Braaf, LM, Winterhoff, B, Nevanlinna, H, Konecny, GE, Lambrechts, D, Rogmann, L, Guenel, P, Teoman, A, Milne, RL, Garcia, JJ, Cox, A, Shridhar, V, Burwinkel, B, Marme, F, Hein, R, Sawyer, EJ, Haiman, CA, Wang-Gohrke, S, Andrulis, IL, Moysich, KB, Hopper, JL, Odunsi, K, Lindblom, A, Giles, GG, Brenner, H, Simard, J, Lurie, G, Fasching, PA, Carney, ME, Radice, P, Wilkens, LR, Swerdlow, A, Goodman, MT, Brauch, H, Garcia-Closas, M, Hillemanns, P, Winqvist, R, Durst, M, Devilee, P, Runnebaum, I, Jakubowska, A, Lubinski, J, Mannermaa, A, Butzow, R, Bogdanova, NV, Dork, T, Pelttari, LM, Zheng, W, Leminen, A, Anton-Culver, H, Bunker, CH, Kristensen, V, Ness, RB, Muir, K, Edwards, R, Meind, A, Heitz, F, Matsuo, K, du Blois, A, Wu, AH, Harter, P, Teo, SH, Schwaab, I, Shu, XO, Blot, W, Hosono, S, Kang, D, Nakanishi, T, Hartman, M, Yatabe, Y, Hamann, U, Karlan, BY, Sangrajrang, S, Kjaer, SK, Gaborieau, V, Jensen, A, Eccles, D, Hogdall, E, Shen, CY, Brown, J, Woo, YL, Shah, M, Azmi, MAN, Luben, R, Omar, SZ, Czene, K, Vierkant, RA, Nordestgaard, BG, Flyger, H, Vachon, C, Olson, JE, Wang, XS, Levine, DA, Rudolph, A, Weber, RP, Flesch-Janys, D, Iversen, E, Nickels, S, Schildkraut, JM, Silva, ID, Cramer, DW, Gibson, L, Terry, KL, Fletcher, O, Vitonis, AF, van der Schoot, CE, Poole, EM, Hogervorst, FBL, Tworoger, SS, Liu, JJ, Bandera, EV, Li, JM, Olson, SH, Humphreys, K, Row, I, Blomqvist, C, Rodriguez-Rodriguez, L, Aittomaki, K, Salvesen, HB, Muranen, TA, Wik, E, Brouwers, B, Krakstad, C, Wauters, E, Halle, MK, Wildiers, H, Kiemeney, LA, Mulot, C, Aben, KK, Laurent-Puig, P, van Altena, AM, Truong, T, Massuger, LFAG, Benitez, J, Pejovic, T, Perez, JIA, Hoatlin, M, Zamora, MP, Cook, LS, Balasubramanian, SP, Kelemen, LE, Schneeweiss, A, Le, ND, Sohn, C, Brooks-Wilson, A, Tomlinson, I, Kerin, MJ, Miller, N, Cybulski, C, Henderson, BE, Menkiszak, J, Schumacher, FR, Wentzensen, N, Le Marchand, L, Yang, HP, Mulligan, AM, Glendon, G, Engelholm, SA, Knight, JA, Hogdall, CK, Apicella, C, Gore, M, Tsimiklis, H, Song, HL, Southey, MC, Jager, A, van den Ouweland, A, Brown, R, Martens, J, Flanagan, JM, Kriege, M, Paul, J, Margolin, S, Siddiqui, N, Severi, G, Whittemore, AS, Baglietto, L, McGuire, V, Stegmaier, C, Sieh, W, Muller, H, Arndt, V, Labreche, F, Gao, YT, Goldberg, MS, Dumont, M, McLaughlin, JR, Hartmann, A, Ekici, AB, Beckmann, MW, Phelan, CM, Lux, MP, Permuth-Wey, J, Peissel, B, Sellers, TA, Ficarazzi, F, Barile, M, Ziogas, A, Ashworth, A, Gentry-Maharaj, A, Jones, M, Ramus, SJ, Orr, N, Menon, U, Pearce, CL, Bruning, T, Pike, MC, Ko, YD, Lissowska, J, Figueroa, J, Kupryjanczyk, J, Chanock, SJ, Dansonka-Mieszkowska, A, Jukkola-Vuorinen, A, Rzepecka, IK, Pylkas, K, Bidzinski, M, Kauppila, S, Hollestelle, A, Seynaeve, C, Tollenaar, RAEM, Durda, K, Jaworska, K, Hartikainen, JM, Kosma, VM, Kataja, V, Antonenkova, NN, Long, JR, Shrubsole, M, Deming-Halverson, S, Lophatananon, A, Siriwanarangsan, P, Stewart-Brown, S, Ditsch, N, Lichtner, P, Schmutzler, RK, Ito, H, Iwata, H, Tajima, K, Tseng, CC, Stram, DO, van den Berg, D, Yip, CH, Ikrarn, MK, Cai, H, Lu, W, Signorello, LB, Cai, QY, Noh, DY, Yoo, KY, Miao, H, Iau, PTC, Teo, YY, Mckay, J, Shapiro, C, Ademuyiwa, F, Fountzilas, G, Hsiung, CN, Yu, JC, Hou, MF, Healey, CS, Luccarini, C, Peock, S, Stoppa-Lyonnet, D, Peterlongo, P, Rebbeck, TR, Piedmonte, M, Singer, CF, Friedman, E, Thomassen, M, Offit, K, Hansen, TVO, Neuhausen, SL, Szabo, CI, Blanco, I, Garber, J, Narod, SA, Weitzel, JN, Montagna, M, Olah, E, Godwin, AK, Yannoukakos, D, Goldgar, DE, Caldes, T, Imyanitov, EN, Tihomirova, L, Arun, BK, Campbell, I, Mensenkamp, AR, van Asperen, CJ, van Roozendaa, KEP, Meijers-Heijboer, H, Collee, M, Oosterwijk, JC, Hooning, M, Rookus, MA, van der Luijt, RB, van Os, TAM, Evans, DG, Frost, D, Fineberg, E, Barwell, J, Walker, L, Kennedy, MJ, Platte, R, Davidson, R, Ellis, SD, Cole, T, Bressac-de Paillerets, B, Buecher, B, Damiola, F, Faivre, L, Frenay, M, Sinilnikova, OM, Caron, O, Giraud, S, Mazoyer, S, Bonadona, V, Caux-Moncoutier, V, Toloczko-Grabarek, A, Gronwald, J, Byrski, T, Spurdle, AB, Bonanni, B, Zaffaroni, D, Giannini, G, Bernard, L, Dolcetti, R, Manoukian, S, Arnold, N, Engel, C, Deissler, H, Rhiem, K, Niederacher, D, Pendl, H, Sutter, C, Wappenschmidt, B, Borg, A, Mein, B, Rantala, J, Soller, M, Nathanson, KL, Domchek, SM, Rodriguez, GC, Salani, R, Kaulich, DG, Tea, MK, Paluch, SS, Laitman, Y, Skytte, AB, Kruse, TA, Jensen, UB, Robson, M, Gerdes, AM, Ejlertsen, B, Foretova, L, Savage, SA, Lesterm, J, Soucy, P, Kuchenbaecker, KB, Olswold, C, Cunningham, JM, Slager, S, Pankratz, VS, Dicks, E, Lakhani, SR, Couch, FJ, Hall, P, Monteiro, ANA, Gayther, SA, Pharoah, PDP, Reddel, RR, Goode, EL, Greene, MH, Easton, DF, Berchuck, A, Antoniou, AC, Chenevix-Trench, G & Dunning, AM 2013, 'Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer', Nature Genetics, vol. 45, no. 4, pp. 371-384. https://doi.org/10.1038/ng.2566

TY - JOUR

T1 - Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer

AU - Bojesen, SE

AU - Teh, YC

AU - Pooley, KA

AU - Johnatty, SE

AU - Beesley, J

AU - Michailidou, K

AU - Tyrer, JP

AU - Edwards, SL

AU - Pickett, HA

AU - Shen, HC

AU - Smart, CE

AU - Hillman, KM

AU - Mai, PL

AU - Lawrenson, K

AU - Stutz, MD

AU - Lu, Y

AU - Karevan, R

AU - Woods, N

AU - Johnstonw, RL

AU - French, JD

AU - Chen, XQ

AU - Weischer, M

AU - Nielsen, SF

AU - Maranian, MJ

AU - Ghoussaini, M

AU - Ahmed, S (Shahana)

AU - Baynes, C

AU - Bolla, MK

AU - Wang, Q (Qing)

AU - Dennis, J

AU - McGuffog, L

AU - Barrowdale, D

AU - van der Lee, A

AU - Healey, S

AU - Lush, M

AU - Tessier, DC

AU - Vincent, D

AU - Bacot, F

AU - Vergote, I

AU - Lambrechts, S

AU - Despierre, E

AU - Risch, HA

AU - Gonzaalez-Neira, A

AU - Rossing, MA

AU - Pita, G

AU - Doherty, JA

AU - Alvarez, N

AU - Larson, MC

AU - Fridley, BL

AU - Schoof, N

AU - Chang-Claude, J

AU - Cicek, MS

AU - Peto, J

AU - Kalli, KR

AU - Broeks, A

AU - Armasu, SM

AU - Schmidt, Marjanka K

AU - Braaf, LM

AU - Winterhoff, B

AU - Nevanlinna, H

AU - Konecny, GE

AU - Lambrechts, D

AU - Rogmann, L

AU - Guenel, P

AU - Teoman, A

AU - Milne, RL

AU - Garcia, JJ

AU - Cox, A

AU - Shridhar, V

AU - Burwinkel, B

AU - Marme, F

AU - Hein, R

AU - Sawyer, EJ

AU - Haiman, CA

AU - Wang-Gohrke, S

AU - Andrulis, IL

AU - Moysich, KB

AU - Hopper, JL

AU - Odunsi, K

AU - Lindblom, A

AU - Giles, GG

AU - Brenner, H

AU - Simard, J

AU - Lurie, G

AU - Fasching, PA

AU - Carney, ME

AU - Radice, P

AU - Wilkens, LR

AU - Swerdlow, A

AU - Goodman, MT

AU - Brauch, H

AU - Garcia-Closas, M

AU - Hillemanns, P

AU - Winqvist, R

AU - Durst, M

AU - Devilee, P

AU - Runnebaum, I

AU - Jakubowska, A

AU - Lubinski, J

AU - Mannermaa, A

AU - Butzow, R

AU - Bogdanova, NV

AU - Dork, T

AU - Pelttari, LM

AU - Zheng, W

AU - Leminen, A

AU - Anton-Culver, H

AU - Bunker, CH

AU - Kristensen, V

AU - Ness, RB

AU - Muir, K

AU - Edwards, R

AU - Meind, A

AU - Heitz, F

AU - Matsuo, K

AU - du Blois, A

AU - Wu, AH

AU - Harter, P

AU - Teo, SH

AU - Schwaab, I

AU - Shu, XO

AU - Blot, W

AU - Hosono, S

AU - Kang, D

AU - Nakanishi, T

AU - Hartman, M

AU - Yatabe, Y

AU - Hamann, U

AU - Karlan, BY

AU - Sangrajrang, S

AU - Kjaer, SK

AU - Gaborieau, V

AU - Jensen, A

AU - Eccles, D

AU - Hogdall, E

AU - Shen, CY

AU - Brown, J

AU - Woo, YL

AU - Shah, M

AU - Azmi, MAN

AU - Luben, R

AU - Omar, SZ

AU - Czene, K

AU - Vierkant, RA

AU - Nordestgaard, BG

AU - Flyger, H

AU - Vachon, C

AU - Olson, JE

AU - Wang, XS

AU - Levine, DA

AU - Rudolph, A

AU - Weber, RP

AU - Flesch-Janys, D

AU - Iversen, E

AU - Nickels, S

AU - Schildkraut, JM

AU - Silva, ID

AU - Cramer, DW

AU - Gibson, L

AU - Terry, KL

AU - Fletcher, O

AU - Vitonis, AF

AU - van der Schoot, CE

AU - Poole, EM

AU - Hogervorst, FBL

AU - Tworoger, SS

AU - Liu, JJ

AU - Bandera, EV

AU - Li, JM

AU - Olson, SH

AU - Humphreys, K

AU - Row, I

AU - Blomqvist, C

AU - Rodriguez-Rodriguez, L

AU - Aittomaki, K

AU - Salvesen, HB

AU - Muranen, TA

AU - Wik, E

AU - Brouwers, B

AU - Krakstad, C

AU - Wauters, Erwin

AU - Halle, MK

AU - Wildiers, H

AU - Kiemeney, LA

AU - Mulot, C

AU - Aben, KK

AU - Laurent-Puig, P

AU - van Altena, AM

AU - Truong, T

AU - Massuger, LFAG

AU - Benitez, J

AU - Pejovic, T

AU - Perez, JIA

AU - Hoatlin, M

AU - Zamora, MP

AU - Cook, LS

AU - Balasubramanian, SP

AU - Kelemen, LE

AU - Schneeweiss, A

AU - Le, ND

AU - Sohn, C

AU - Brooks-Wilson, A

AU - Tomlinson, I

AU - Kerin, MJ

AU - Miller, N

AU - Cybulski, C

AU - Henderson, BE

AU - Menkiszak, J

AU - Schumacher, FR

AU - Wentzensen, N

AU - Le Marchand, L

AU - Yang, HP (Hannah)

AU - Mulligan, AM

AU - Glendon, G

AU - Engelholm, SA

AU - Knight, JA

AU - Hogdall, CK

AU - Apicella, C

AU - Gore, M

AU - Tsimiklis, H

AU - Song, HL

AU - Southey, MC

AU - Jager, Agnes

AU - van den Ouweland, Ans

AU - Brown, R

AU - Martens, John

AU - Flanagan, JM

AU - Kriege, Mieke

AU - Paul, J

AU - Margolin, S

AU - Siddiqui, N

AU - Severi, G

AU - Whittemore, AS

AU - Baglietto, L

AU - McGuire, V

AU - Stegmaier, C

AU - Sieh, W

AU - Muller, H

AU - Arndt, V

AU - Labreche, F

AU - Gao, YT

AU - Goldberg, MS

AU - Dumont, M

AU - McLaughlin, JR

AU - Hartmann, A

AU - Ekici, AB

AU - Beckmann, MW

AU - Phelan, CM

AU - Lux, MP

AU - Permuth-Wey, J

AU - Peissel, B

AU - Sellers, TA

AU - Ficarazzi, F

AU - Barile, M

AU - Ziogas, A

AU - Ashworth, A

AU - Gentry-Maharaj, A

AU - Jones, M

AU - Ramus, SJ

AU - Orr, N

AU - Menon, U

AU - Pearce, CL

AU - Bruning, T

AU - Pike, MC

AU - Ko, YD

AU - Lissowska, J

AU - Figueroa, J

AU - Kupryjanczyk, J

AU - Chanock, SJ

AU - Dansonka-Mieszkowska, A

AU - Jukkola-Vuorinen, A

AU - Rzepecka, IK

AU - Pylkas, K

AU - Bidzinski, M

AU - Kauppila, S

AU - Hollestelle, Antoinette

AU - Seynaeve, Caroline

AU - Tollenaar, RAEM

AU - Durda, K

AU - Jaworska, K

AU - Hartikainen, JM

AU - Kosma, VM

AU - Kataja, V

AU - Antonenkova, NN

AU - Long, JR

AU - Shrubsole, M

AU - Deming-Halverson, S

AU - Lophatananon, A

AU - Siriwanarangsan, P

AU - Stewart-Brown, S

AU - Ditsch, N

AU - Lichtner, P

AU - Schmutzler, RK

AU - Ito, H

AU - Iwata, H

AU - Tajima, K

AU - Tseng, CC

AU - Stram, DO

AU - van den Berg, D

AU - Yip, CH

AU - Ikrarn, MK

AU - Cai, H

AU - Lu, W

AU - Signorello, LB

AU - Cai, QY

AU - Noh, DY

AU - Yoo, KY

AU - Miao, H

AU - Iau, PTC

AU - Teo, YY

AU - Mckay, J

AU - Shapiro, C

AU - Ademuyiwa, F

AU - Fountzilas, G

AU - Hsiung, CN

AU - Yu, JC

AU - Hou, MF

AU - Healey, CS

AU - Luccarini, C

AU - Peock, S

AU - Stoppa-Lyonnet, D

AU - Peterlongo, P

AU - Rebbeck, TR

AU - Piedmonte, M

AU - Singer, CF

AU - Friedman, E

AU - Thomassen, Marga

AU - Offit, K

AU - Hansen, TVO

AU - Neuhausen, SL

AU - Szabo, CI

AU - Blanco, I

AU - Garber, J

AU - Narod, SA

AU - Weitzel, JN

AU - Montagna, M

AU - Olah, E

AU - Godwin, AK

AU - Yannoukakos, D

AU - Goldgar, DE

AU - Caldes, T

AU - Imyanitov, EN

AU - Tihomirova, L

AU - Arun, BK

AU - Campbell, I

AU - Mensenkamp, AR

AU - van Asperen, CJ

AU - van Roozendaa, KEP

AU - Meijers-Heijboer, H

AU - Collee, Margriet

AU - Oosterwijk, JC

AU - Hooning, Maartje

AU - Rookus, MA

AU - van der Luijt, RB

AU - van Os, TAM

AU - Evans, DG

AU - Frost, D

AU - Fineberg, E

AU - Barwell, J

AU - Walker, L

AU - Kennedy, MJ

AU - Platte, R

AU - Davidson, R

AU - Ellis, SD

AU - Cole, T

AU - Bressac-de Paillerets, B

AU - Buecher, B

AU - Damiola, F

AU - Faivre, L

AU - Frenay, M

AU - Sinilnikova, OM

AU - Caron, O (Olivier)

AU - Giraud, S

AU - Mazoyer, S

AU - Bonadona, V

AU - Caux-Moncoutier, V

AU - Toloczko-Grabarek, A

AU - Gronwald, J

AU - Byrski, T

AU - Spurdle, AB

AU - Bonanni, B

AU - Zaffaroni, D

AU - Giannini, G

AU - Bernard, L

AU - Dolcetti, R

AU - Manoukian, S

AU - Arnold, N

AU - Engel, C

AU - Deissler, H

AU - Rhiem, K

AU - Niederacher, D

AU - Pendl, H

AU - Sutter, C

AU - Wappenschmidt, B

AU - Borg, A

AU - Mein, B

AU - Rantala, J

AU - Soller, M

AU - Nathanson, KL

AU - Domchek, SM

AU - Rodriguez, GC

AU - Salani, R

AU - Kaulich, DG

AU - Tea, MK

AU - Paluch, SS

AU - Laitman, Y

AU - Skytte, AB

AU - Kruse, TA

AU - Jensen, UB

AU - Robson, M

AU - Gerdes, AM

AU - Ejlertsen, B

AU - Foretova, L

AU - Savage, SA

AU - Lesterm, J

AU - Soucy, P

AU - Kuchenbaecker, KB

AU - Olswold, C

AU - Cunningham, JM

AU - Slager, S

AU - Pankratz, VS

AU - Dicks, E

AU - Lakhani, SR

AU - Couch, FJ

AU - Hall, P

AU - Monteiro, ANA

AU - Gayther, SA

AU - Pharoah, PDP

AU - Reddel, RR

AU - Goode, EL

AU - Greene, MH

AU - Easton, DF

AU - Berchuck, A

AU - Antoniou, AC

AU - Chenevix-Trench, G

AU - Dunning, AM

PY - 2013

Y1 - 2013

N2 - TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOG, we analyzed similar to 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 x 10(-7)), lower risks for estrogen receptor (ER)-negative (P = 1.0 x 10(-8)) and BRCA1 mutation carrier (P = 1.1 x 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 x 10(-14)), higher risk of low-malignant-potential ovarian cancer (P = 1.3 x 10(-15)) and greater promoter activity. The minor alleles at the peak 3 SNPs rs10069690 and rs2242652 increase ER-negative (P = 1.2 x 10(-12)) and BRCA1 mutation carrier (P = 1.6 x 10-14) breast and invasive ovarian (P = 1.3 x 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.

AB - TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOG, we analyzed similar to 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 x 10(-7)), lower risks for estrogen receptor (ER)-negative (P = 1.0 x 10(-8)) and BRCA1 mutation carrier (P = 1.1 x 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 x 10(-14)), higher risk of low-malignant-potential ovarian cancer (P = 1.3 x 10(-15)) and greater promoter activity. The minor alleles at the peak 3 SNPs rs10069690 and rs2242652 increase ER-negative (P = 1.2 x 10(-12)) and BRCA1 mutation carrier (P = 1.6 x 10-14) breast and invasive ovarian (P = 1.3 x 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.

U2 - 10.1038/ng.2566

DO - 10.1038/ng.2566

M3 - Article

C2 - 23535731

SN - 1061-4036

VL - 45

SP - 371

EP - 384

JO - Nature Genetics

JF - Nature Genetics

IS - 4

ER -

Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer

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