Lymphocyte telomere length is long in BRCA1 and BRCA2 mutation carriers regardless of cancer-affected status

2.50
Hdl Handle:
http://hdl.handle.net/11287/593870
Title:
Lymphocyte telomere length is long in BRCA1 and BRCA2 mutation carriers regardless of cancer-affected status
Authors:
Pooley, K. A.; McGuffog, L.; Barrowdale, D.; Frost, D.; Ellis, S. D.; Fineberg, E.; Platte, R.; Izatt, L.; Adlard, J.; Bardwell, J.; Brewer, Carole; Cole, T.; Cook, J.; Davidson, R.; Donaldson, A.; Dorkins, H.; Douglas, F.; Eason, J.; Houghton, C.; Kennedy, M. J.; McCann, E.; Miedzybrodzka, Z.; Murray, Anna; Porteous, M. E.; Rogers, M. T.; Side, L. E.; Tischkowitz, M.; Walker, L.; Hodgson, S.; Eccles, D. M.; Morrison, P. J.; Evans, D. G.; Eeles, R. A.; Antoniou, A. C.; Easton, D. F.; Dunning, A. M.; Embrace,
Abstract:
BACKGROUND: Telomere length has been linked to risk of common diseases, including cancer, and has previously been proposed as a biomarker for cancer risk. Germline BRCA1 and BRCA2 mutations predispose to breast, ovarian, and other cancer types. METHODS: We investigated telomere length in BRCA mutation carriers and their non-carrier relatives and further examined whether telomere length is a modifier of cancer risk in mutation carriers. We measured mean telomere length in DNA extracted from whole blood using high-throughput quantitative PCR. Participants were from the EMBRACE study in United Kingdom and Eire (n = 4,822) and comprised BRCA1 (n = 1,628) and BRCA2 (n = 1,506) mutation carriers and their non-carrier relatives (n = 1,688). RESULTS: We find no significant evidence that mean telomere length is associated with breast or ovarian cancer risk in BRCA mutation carriers. However, we find mutation carriers to have longer mean telomere length than their non-carrier relatives (all carriers vs. non-carriers, Ptrend = 0.0018), particularly in families with BRCA2 mutations (BRCA2 mutation carriers vs. all non-carriers, Ptrend = 0.0016). CONCLUSIONS: Our findings lend little support to the hypothesis that short mean telomere length predisposes to cancer. Conversely, our main and unexpected finding is that BRCA mutation carriers (regardless of cancer status) have longer telomeres than their non-mutation carrier, non-cancer-affected relatives. The longer telomere length in BRCA2 mutation carriers is consistent with its role in DNA damage response. Overall, it seems that increased telomere length may be a consequence of these mutations, but is not itself directly related to the increased cancer risk in carriers. IMPACT: The finding that mutation carriers have longer mean telomere lengths than their non-carrier relatives is unexpected but biologically plausible and could open up new lines of research into the functions of the BRCA proteins. To our knowledge, this is the largest study of telomere length in BRCA mutation carriers and their relatives. The null cancer-risk association supports recent large prospective studies of breast and ovarian cancer and indicates that mean telomere length would not be a useful biomarker in these cancers. Cancer Epidemiol Biomarkers Prev; 23(6); 1018-24. (c)2014 AACR.
Citation:
Cancer Epidemiol Biomarkers Prev. 2014 Jun;23(6):1018-24.
Publisher:
Cancer Epidemiol Biomarkers Prev
Journal:
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Issue Date:
1-Jun-2014
URI:
http://hdl.handle.net/11287/593870
DOI:
10.1158/1055-9965.EPI-13-0635-T
PubMed ID:
24642354
Additional Links:
http://cebp.aacrjournals.org/cgi/pmidlookup?view=long&pmid=24642354
Note:
This article is available via Open Access. Please click on the 'Additional Link' above to access the full-text.
Type:
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Language:
eng
ISSN:
1538-7755
Appears in Collections:
2014 RD&E publications; Clinical Genetics (Peninsula Genetics)

Full metadata record

DC FieldValue Language
dc.contributor.authorPooley, K. A.en
dc.contributor.authorMcGuffog, L.en
dc.contributor.authorBarrowdale, D.en
dc.contributor.authorFrost, D.en
dc.contributor.authorEllis, S. D.en
dc.contributor.authorFineberg, E.en
dc.contributor.authorPlatte, R.en
dc.contributor.authorIzatt, L.en
dc.contributor.authorAdlard, J.en
dc.contributor.authorBardwell, J.en
dc.contributor.authorBrewer, Caroleen
dc.contributor.authorCole, T.en
dc.contributor.authorCook, J.en
dc.contributor.authorDavidson, R.en
dc.contributor.authorDonaldson, A.en
dc.contributor.authorDorkins, H.en
dc.contributor.authorDouglas, F.en
dc.contributor.authorEason, J.en
dc.contributor.authorHoughton, C.en
dc.contributor.authorKennedy, M. J.en
dc.contributor.authorMcCann, E.en
dc.contributor.authorMiedzybrodzka, Z.en
dc.contributor.authorMurray, Annaen
dc.contributor.authorPorteous, M. E.en
dc.contributor.authorRogers, M. T.en
dc.contributor.authorSide, L. E.en
dc.contributor.authorTischkowitz, M.en
dc.contributor.authorWalker, L.en
dc.contributor.authorHodgson, S.en
dc.contributor.authorEccles, D. M.en
dc.contributor.authorMorrison, P. J.en
dc.contributor.authorEvans, D. G.en
dc.contributor.authorEeles, R. A.en
dc.contributor.authorAntoniou, A. C.en
dc.contributor.authorEaston, D. F.en
dc.contributor.authorDunning, A. M.en
dc.contributor.authorEmbrace,en
dc.date.accessioned2016-01-19T12:36:04Zen
dc.date.available2016-01-19T12:36:04Zen
dc.date.issued2014-06-01en
dc.identifier.citationCancer Epidemiol Biomarkers Prev. 2014 Jun;23(6):1018-24.en
dc.identifier.issn1538-7755en
dc.identifier.pmid24642354en
dc.identifier.doi10.1158/1055-9965.EPI-13-0635-Ten
dc.identifier.urihttp://hdl.handle.net/11287/593870en
dc.description.abstractBACKGROUND: Telomere length has been linked to risk of common diseases, including cancer, and has previously been proposed as a biomarker for cancer risk. Germline BRCA1 and BRCA2 mutations predispose to breast, ovarian, and other cancer types. METHODS: We investigated telomere length in BRCA mutation carriers and their non-carrier relatives and further examined whether telomere length is a modifier of cancer risk in mutation carriers. We measured mean telomere length in DNA extracted from whole blood using high-throughput quantitative PCR. Participants were from the EMBRACE study in United Kingdom and Eire (n = 4,822) and comprised BRCA1 (n = 1,628) and BRCA2 (n = 1,506) mutation carriers and their non-carrier relatives (n = 1,688). RESULTS: We find no significant evidence that mean telomere length is associated with breast or ovarian cancer risk in BRCA mutation carriers. However, we find mutation carriers to have longer mean telomere length than their non-carrier relatives (all carriers vs. non-carriers, Ptrend = 0.0018), particularly in families with BRCA2 mutations (BRCA2 mutation carriers vs. all non-carriers, Ptrend = 0.0016). CONCLUSIONS: Our findings lend little support to the hypothesis that short mean telomere length predisposes to cancer. Conversely, our main and unexpected finding is that BRCA mutation carriers (regardless of cancer status) have longer telomeres than their non-mutation carrier, non-cancer-affected relatives. The longer telomere length in BRCA2 mutation carriers is consistent with its role in DNA damage response. Overall, it seems that increased telomere length may be a consequence of these mutations, but is not itself directly related to the increased cancer risk in carriers. IMPACT: The finding that mutation carriers have longer mean telomere lengths than their non-carrier relatives is unexpected but biologically plausible and could open up new lines of research into the functions of the BRCA proteins. To our knowledge, this is the largest study of telomere length in BRCA mutation carriers and their relatives. The null cancer-risk association supports recent large prospective studies of breast and ovarian cancer and indicates that mean telomere length would not be a useful biomarker in these cancers. Cancer Epidemiol Biomarkers Prev; 23(6); 1018-24. (c)2014 AACR.en
dc.language.isoengen
dc.publisherCancer Epidemiol Biomarkers Preven
dc.relation.urlhttp://cebp.aacrjournals.org/cgi/pmidlookup?view=long&pmid=24642354en
dc.titleLymphocyte telomere length is long in BRCA1 and BRCA2 mutation carriers regardless of cancer-affected statusen
dc.typeJournal Articleen
dc.typeResearch Support, N.I.H., Extramuralen
dc.typeResearch Support, Non-U.S. Gov'ten
dc.identifier.journalCancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncologyen
dc.description.noteThis article is available via Open Access. Please click on the 'Additional Link' above to access the full-text.en

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