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A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor-negative breast cancer.


ABSTRACT: Estrogen receptor (ER)-negative breast cancer shows a higher incidence in women of African ancestry compared to women of European ancestry. In search of common risk alleles for ER-negative breast cancer, we combined genome-wide association study (GWAS) data from women of African ancestry (1,004 ER-negative cases and 2,745 controls) and European ancestry (1,718 ER-negative cases and 3,670 controls), with replication testing conducted in an additional 2,292 ER-negative cases and 16,901 controls of European ancestry. We identified a common risk variant for ER-negative breast cancer at the TERT-CLPTM1L locus on chromosome 5p15 (rs10069690: per-allele odds ratio (OR) = 1.18 per allele, P = 1.0 × 10(-10)). The variant was also significantly associated with triple-negative (ER-negative, progesterone receptor (PR)-negative and human epidermal growth factor-2 (HER2)-negative) breast cancer (OR = 1.25, P = 1.1 × 10(-9)), particularly in younger women (<50 years of age) (OR = 1.48, P = 1.9 × 10(-9)). Our results identify a genetic locus associated with estrogen receptor negative breast cancer subtypes in multiple populations.

SUBMITTER: Haiman CA 

PROVIDER: S-EPMC3279120 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor-negative breast cancer.

Haiman Christopher A CA   Chen Gary K GK   Vachon Celine M CM   Canzian Federico F   Dunning Alison A   Millikan Robert C RC   Wang Xianshu X   Ademuyiwa Foluso F   Ahmed Shahana S   Ambrosone Christine B CB   Baglietto Laura L   Balleine Rosemary R   Bandera Elisa V EV   Beckmann Matthias W MW   Berg Christine D CD   Bernstein Leslie L   Blomqvist Carl C   Blot William J WJ   Brauch Hiltrud H   Buring Julie E JE   Carey Lisa A LA   Carpenter Jane E JE   Chang-Claude Jenny J   Chanock Stephen J SJ   Chasman Daniel I DI   Clarke Christine L CL   Cox Angela A   Cross Simon S SS   Deming Sandra L SL   Diasio Robert B RB   Dimopoulos Athanasios M AM   Driver W Ryan WR   Dünnebier Thomas T   Durcan Lorraine L   Eccles Diana D   Edlund Christopher K CK   Ekici Arif B AB   Fasching Peter A PA   Feigelson Heather S HS   Flesch-Janys Dieter D   Fostira Florentia F   Försti Asta A   Fountzilas George G   Gerty Susan M SM   Giles Graham G GG   Godwin Andrew K AK   Goodfellow Paul P   Graham Nikki N   Greco Dario D   Hamann Ute U   Hankinson Susan E SE   Hartmann Arndt A   Hein Rebecca R   Heinz Judith J   Holbrook Andrea A   Hoover Robert N RN   Hu Jennifer J JJ   Hunter David J DJ   Ingles Sue A SA   Irwanto Astrid A   Ivanovich Jennifer J   John Esther M EM   Johnson Nicola N   Jukkola-Vuorinen Arja A   Kaaks Rudolf R   Ko Yon-Dschun YD   Kolonel Laurence N LN   Konstantopoulou Irene I   Kosma Veli-Matti VM   Kulkarni Swati S   Lambrechts Diether D   Lee Adam M AM   Marchand Loïc Le LL   Lesnick Timothy T   Liu Jianjun J   Lindstrom Sara S   Mannermaa Arto A   Margolin Sara S   Martin Nicholas G NG   Miron Penelope P   Montgomery Grant W GW   Nevanlinna Heli H   Nickels Stephan S   Nyante Sarah S   Olswold Curtis C   Palmer Julie J   Pathak Harsh H   Pectasides Dimitrios D   Perou Charles M CM   Peto Julian J   Pharoah Paul D P PD   Pooler Loreall C LC   Press Michael F MF   Pylkäs Katri K   Rebbeck Timothy R TR   Rodriguez-Gil Jorge L JL   Rosenberg Lynn L   Ross Eric E   Rüdiger Thomas T   Silva Isabel dos Santos Idos S   Sawyer Elinor E   Schmidt Marjanka K MK   Schulz-Wendtland Rüdiger R   Schumacher Fredrick F   Severi Gianluca G   Sheng Xin X   Signorello Lisa B LB   Sinn Hans-Peter HP   Stevens Kristen N KN   Southey Melissa C MC   Tapper William J WJ   Tomlinson Ian I   Hogervorst Frans B L FB   Wauters Els E   Weaver JoEllen J   Wildiers Hans H   Winqvist Robert R   Van Den Berg David D   Wan Peggy P   Xia Lucy Y LY   Yannoukakos Drakoulis D   Zheng Wei W   Ziegler Regina G RG   Siddiq Afshan A   Slager Susan L SL   Stram Daniel O DO   Easton Douglas D   Kraft Peter P   Henderson Brian E BE   Couch Fergus J FJ  

Nature genetics 20111030 12


Estrogen receptor (ER)-negative breast cancer shows a higher incidence in women of African ancestry compared to women of European ancestry. In search of common risk alleles for ER-negative breast cancer, we combined genome-wide association study (GWAS) data from women of African ancestry (1,004 ER-negative cases and 2,745 controls) and European ancestry (1,718 ER-negative cases and 3,670 controls), with replication testing conducted in an additional 2,292 ER-negative cases and 16,901 controls of  ...[more]

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