TY - JOUR
T1 - Telomere length, ATM mutation status and cancer risk in Ataxia-Telangiectasia families
AU - Renault, Anne Laure
AU - Mebirouk, Noura
AU - Cavaciuti, Eve
AU - Le Gal, Dorothée
AU - Lecarpentier, Julie
AU - Dubois d'Enghien, Catherine
AU - Laugé, Anthony
AU - Dondon, Marie Gabrielle
AU - Labbé, Martine
AU - Lesca, Gaetan
AU - Leroux, Dominique
AU - Gladieff, Laurence
AU - Adenis, Claude
AU - Faivre, Laurence
AU - Gilbert-Dussardier, Brigitte
AU - Lortholary, Alain
AU - Fricker, Jean Pierre
AU - Dahan, Karin
AU - Bay, Jacques Olivier
AU - Longy, Michel
AU - Buecher, Bruno
AU - Janin, Nicolas
AU - Zattara, Hélène
AU - Berthet, Pascaline
AU - Combès, Audrey
AU - Coupier, Isabelle
AU - CoF-AT study collaborators
AU - Hall, Janet
AU - Stoppa-Lyonnet, Dominique
AU - Andrieu, Nadine
AU - Lesueur, Fabienne
PY - 2017/10/1
Y1 - 2017/10/1
N2 - Recent studies have linked constitutive telomere length (TL) to aging-related diseases including cancer at different sites. ATM participates in the signaling of telomere erosion, and inherited mutations in ATM have been associated with increased risk of cancer, particularly breast cancer. The goal of this study was to investigate whether carriage of an ATM mutation and TL interplay to modify cancer risk in ataxia-telangiectasia (A-T) families. The study population consisted of 284 heterozygous ATM mutation carriers (HetAT) and 174 non-carriers (non-HetAT) from 103 A-T families. Forty-eight HetAT and 14 non-HetAT individuals had cancer, among them 25 HetAT and 6 non-HetAT were diagnosed after blood sample collection. We measured mean TL using a quantitative PCR assay and genotyped seven single-nucleotide polymorphisms (SNPs) recurrently associated with TL in large population-based studies. HetAT individuals were at increased risk of cancer (OR = 2.3, 95%CI = 1.2-4.4, P = 0.01), and particularly of breast cancer for women (OR = 2.9, 95%CI = 1.2-7.1, P = 0.02), in comparison to their non-HetAT relatives. HetAT individuals had longer telomeres than non-HetAT individuals (P = 0.0008) but TL was not associated with cancer risk, and no significant interaction was observed between ATM mutation status and TL. Furthermore, rs9257445 (ZNF311) was associated with TL in HetAT subjects and rs6060627 (BCL2L1) modified cancer risk in HetAT and non-HetAT women. Our findings suggest that carriage of an ATM mutation impacts on the age-related TL shortening and that TL per se is not related to cancer risk in ATM carriers. TL measurement alone is not a good marker for predicting cancer risk in A-T families.
AB - Recent studies have linked constitutive telomere length (TL) to aging-related diseases including cancer at different sites. ATM participates in the signaling of telomere erosion, and inherited mutations in ATM have been associated with increased risk of cancer, particularly breast cancer. The goal of this study was to investigate whether carriage of an ATM mutation and TL interplay to modify cancer risk in ataxia-telangiectasia (A-T) families. The study population consisted of 284 heterozygous ATM mutation carriers (HetAT) and 174 non-carriers (non-HetAT) from 103 A-T families. Forty-eight HetAT and 14 non-HetAT individuals had cancer, among them 25 HetAT and 6 non-HetAT were diagnosed after blood sample collection. We measured mean TL using a quantitative PCR assay and genotyped seven single-nucleotide polymorphisms (SNPs) recurrently associated with TL in large population-based studies. HetAT individuals were at increased risk of cancer (OR = 2.3, 95%CI = 1.2-4.4, P = 0.01), and particularly of breast cancer for women (OR = 2.9, 95%CI = 1.2-7.1, P = 0.02), in comparison to their non-HetAT relatives. HetAT individuals had longer telomeres than non-HetAT individuals (P = 0.0008) but TL was not associated with cancer risk, and no significant interaction was observed between ATM mutation status and TL. Furthermore, rs9257445 (ZNF311) was associated with TL in HetAT subjects and rs6060627 (BCL2L1) modified cancer risk in HetAT and non-HetAT women. Our findings suggest that carriage of an ATM mutation impacts on the age-related TL shortening and that TL per se is not related to cancer risk in ATM carriers. TL measurement alone is not a good marker for predicting cancer risk in A-T families.
UR - http://www.scopus.com/inward/record.url?scp=85032440177&partnerID=8YFLogxK
U2 - 10.1093/carcin/bgx074
DO - 10.1093/carcin/bgx074
M3 - Article
C2 - 28981872
AN - SCOPUS:85032440177
SN - 0143-3334
VL - 38
SP - 994
EP - 1003
JO - Carcinogenesis
JF - Carcinogenesis
IS - 10
M1 - bgx074
ER -
