PALB2, CHEK2 and ATM rare variants and cancer risk : data from COGS

Show full item record



Permalink

http://hdl.handle.net/10138/174957

Citation

Southey , M C , Goldgar , D E , Winqvist , R , Pylkas , K , Couch , F , Tischkowitz , M , Foulkes , W D , Dennis , J , Michailidou , K , van Rensburg , E J , Heikkinen , T , Nevanlinna , H , Hopper , J L , Doerk , T , Claes , K B M , Reis-Filho , J , Teo , Z L , Radice , P , Catucci , I , Peterlongo , P , Tsimiklis , H , Odefrey , F A , Dowty , J G , Schmidt , M K , Broeks , A , Hogervorst , F B , Verhoef , S , Carpenter , J , Clarke , C , Scott , R J , Fasching , P A , Haeberle , L , Ekici , A B , Beckmann , M W , Peto , J , dos-Santos-Silva , I , Fletcher , O , Johnson , N , Bolla , M K , Sawyer , E J , Tomlinson , I , Kerin , M J , Miller , N , Marme , F , Burwinkel , B , Muranen , T A , Aittomäki , K , Blomqvist , C , Pelttari , L M , Butzow , R , kConFab Investigators & Australian Ovarian Canc Study Grp 2016 , ' PALB2, CHEK2 and ATM rare variants and cancer risk : data from COGS ' , Journal of Medical Genetics , vol. 53 , no. 12 , pp. 800-811 . https://doi.org/10.1136/jmedgenet-2016-103839

Title: PALB2, CHEK2 and ATM rare variants and cancer risk : data from COGS
Author: Southey, Melissa C.; Goldgar, David E.; Winqvist, Robert; Pylkas, Katri; Couch, Fergus; Tischkowitz, Marc; Foulkes, William D.; Dennis, Joe; Michailidou, Kyriaki; van Rensburg, Elizabeth J.; Heikkinen, Tuomas; Nevanlinna, Heli; Hopper, John L.; Doerk, Thilo; Claes, Kathleen B. M.; Reis-Filho, Jorge; Teo, Zhi Ling; Radice, Paolo; Catucci, Irene; Peterlongo, Paolo; Tsimiklis, Helen; Odefrey, Fabrice A.; Dowty, James G.; Schmidt, Marjanka K.; Broeks, Annegien; Hogervorst, Frans B.; Verhoef, Senno; Carpenter, Jane; Clarke, Christine; Scott, Rodney J.; Fasching, Peter A.; Haeberle, Lothar; Ekici, Arif B.; Beckmann, Matthias W.; Peto, Julian; dos-Santos-Silva, Isabel; Fletcher, Olivia; Johnson, Nichola; Bolla, Manjeet K.; Sawyer, Elinor J.; Tomlinson, Ian; Kerin, Michael J.; Miller, Nicola; Marme, Federik; Burwinkel, Barbara; Muranen, Taru A.; Aittomäki, Kristiina; Blomqvist, Carl; Pelttari, Liisa M.; Butzow, Ralf; kConFab Investigators; Australian Ovarian Canc Study Grp
Contributor: University of Helsinki, Clinicum
University of Helsinki, Department of Obstetrics and Gynecology
University of Helsinki, Department of Obstetrics and Gynecology
University of Helsinki, Medicum
University of Helsinki, Clinicum
University of Helsinki, Department of Obstetrics and Gynecology
University of Helsinki, Department of Pathology
Date: 2016-12
Language: eng
Number of pages: 12
Belongs to series: Journal of Medical Genetics
ISSN: 0022-2593
URI: http://hdl.handle.net/10138/174957
Abstract: Background The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with rare BRCA2 mutations. We aimed to estimate the relative risks associated with specific rare variants in PALB2, CHEK2 and ATM via a multicentre case-control study. Methods We genotyped 10 rare mutations using the custom iCOGS array: PALB2 c.1592delT, c.2816T>G and c.3113G>A, CHEK2 c.349A>G, c.538C>T, c.715G>A, c.1036C>T, c.1312G>T, and c.1343T>G and ATM c.7271T>G. We assessed associations with breast cancer risk (42 671 cases and 42 164 controls), as well as prostate (22 301 cases and 22 320 controls) and ovarian (14 542 cases and 23 491 controls) cancer risk, for each variant. Results For European women, strong evidence of association with breast cancer risk was observed for PALB2 c.1592delT OR 3.44 (95% CI 1.39 to 8.52, p=7.1x10-5), PALB2 c.3113G>A OR 4.21 (95% CI 1.84 to 9.60, p=6.9x10-8) and ATM c.7271T>G OR 11.0 (95% CI 1.42 to 85.7, p=0.0012). We also found evidence of association with breast cancer risk for three variants in CHEK2, c.349A>G OR 2.26 (95% CI 1.29 to 3.95), c.1036C>T OR 5.06 (95% CI 1.09 to 23.5) and c.538C>T OR 1.33 (95% CI 1.05 to 1.67) (p=0.017). Evidence for prostate cancer risk was observed for CHEK2 c.1343T>G OR 3.03 (95% CI 1.53 to 6.03, p=0.0006) for African men and CHEK2 c.1312G>T OR 2.21 (95% CI 1.06 to 4.63, p=0.030) for European men. No evidence of association with ovarian cancer was found for any of these variants. Conclusions This report adds to accumulating evidence that at least some variants in these genes are associated with an increased risk of breast cancer that is clinically important.
Subject: BREAST-CANCER
PROSTATE-CANCER
OVARIAN-CANCER
BRCA2-INTERACTING PROTEIN
SUSCEPTIBILITY LOCI
FAMILY REGISTRY
GENE
MUTATIONS
BRCA1
METAANALYSIS
3122 Cancers
1184 Genetics, developmental biology, physiology
Rights:


Files in this item

Total number of downloads: Loading...

Files Size Format View
800.full.pdf 428.1Kb PDF View/Open

This item appears in the following Collection(s)

Show full item record