Lymphocyte telomere length is longer in BRCA1 and BRCA2 mutation carriers but does not affect subsequent cancer risk
Menée au Royaume-Uni auprès de 4 822 participantes, cette étude évalue l'association entre la longueur des télomères des lymphocytes et le risque de cancer, en fonction de la présence de mutations BRCA1 ou BRCA2
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 Q-PCR. Participants were from the EMBRACE study in the UK 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, P-trend=0.0018), particularly in families with BRCA2 mutations (BRCA2 mutation carriers vs. all non-carriers, P-trend=0.0016). Conclusions: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 appears 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:Our findings lend little support to the hypothesis that short mean telomere length predisposes to cancer.