Southey MC, Goldgar DE, Winqvist R, Pylkas K, Couch F, Tischkowitz M, Foulkes WD, Dennis J, Michailidou K, Van Rensburg EJ, Heikkinen T, Nevanlinna H, Hopper JL, Doerk T, Claes KBM, Reis-Filho J, Teo ZL, Radice P, Catucci I, Peterlongo P, Tsimiklis H, Odefrey FA, Dowty JG, Schmidt MK, Broeks A, Hogervorst FB, Verhoef S, Carpenter J, Clarke C, Scott RJ, Fasching P, Haeberle L, Ekici AB, Beckmann M, Peto J, Dos-Santos-Silva I, Fletcher O, Johnson N, Bolla MK, Sawyer EJ, Tomlinson I, Kerin MJ, Miller N, Marme F, Burwinkel B, Yang R, Guenel P, Therese Truong , Menegaux F, Sanchez M, Bojesen S, Nielsen SF, Flyger H, Benitez J, Pilar Zamora M, Arias Perez JI, Menendez P, Anton-Culver H, Neuhausen S, Ziogas A, Clarke CA, Brenner H, Arndt V, Stegmaier C, Brauch H, Bruening T, Ko YD, Muranen TA, Aittomaki K, Blomqvist C, Bogdanova NV, Antonenkova NN, Lindblom A, Margolin S, Mannermaa A, Kataja V, Kosma VM, Hartikainen JM, Spurdle AB, Wauters E, Smeets D, Beuselinck B, Floris G, Chang-Claude J, Rudolph A, Seibold P, Flesch-Janys D, Olson JE, Vachon C, Pankratz VS, Mclean C, Haiman CA, Henderson BE, Schumacher F, Le Marchand L, Kristensen V, Alnaes GG, Zheng W, Hunter DJ, Lindstrom S, Hankinson SE, Kraft P, Andrulis I, Knight JA, Glendon G, Mulligan AM, Jukkola-Vuorinen A, Grip M, Kauppila S, Devilee P, Tollenaar RAEM, Seynaeve C, Hollestelle A, Garcia-Closas M, Figueroa J, Chanock SJ, Lissowska J, Czene K, Darabi H, Eriksson M, Eccles DM, Rafiq S, Tapper WJ, Gerty SM, Hooning MJ, Martens JWM, Collee JM, Tilanus-Linthorst M, Hall P, Li J, Brand JS, Humphreys K, Cox A, Reed MWR, Luccarini C, Baynes C, Dunning AM, Hamann U, Torres D, Ulmer HU, Ruediger T, Jakubowska A, Lubinski J, Jaworska K, Durda K, Slager S, Toland AE, Ambrosone CB, Yannoukakos D, Swerdlow A, Ashworth A, Orr N, Jones M, Gonzalez-Neira A, Pita G, Rosario Alonso M, Alvarez N, Herrero D, Tessier DC, Vincent D, Bacot F, Simard J, Dumont M, Soucy P, Eeles R, Muir K, Wiklund F, Gronberg H, Schleutker J, Nordestgaard BG, Weischer M, Travis RC, Neal D, Donovan JL, Hamdy FC, Khaw KT, Stanford JL, Blot WJ, Thibodeau S, Schaid DJ, Kelley JL, Maier C, Kibel AS, Cybulski C, Cannon-Albright L, Butterbach K, Park J, Kaneva R, Batra J, Teixeira MR, Kote-Jarai Z, Al Olama AA, Benlloch S, Renner S, Hartmann A, Hein A, Rübner M, Lambrechts D, Van Nieuwenhuysen E, Vergote I, Lambretchs S, Doherty JA, Rossing MA, Nickels S, Eilber U, Wang-Gohrke S, Odunsi K, Sucheston-Campbell LE, Friel G, Lurie G, Killeen JL, Wilkens LR, Goodman MT, Runnebaum I, Hillemanns PA, Pelttari LM, Butzow R, Modugno F, Edwards RP, Ness RB, Moysich KB, Du Bois A, Heitz F, Harter P, Kommoss S, Karlan BY, Walsh C, Lester J, Jensen A, Kjaer SK, Hogdall E, Peissel B, Bonanni B, Bernard L, Goode EL, Fridley BL, Vierkant RA, Cunningham JM, Larson MC, Fogarty ZC, Kalli KR, Liang D, Lu KH, Hildebrandt MAT, Wu X, Levine DA, Dao F, Bisogna M, Berchuck A, Iversen ES, Marks JR, Akushevich L, Cramer DW, Schildkraut J, Terry KL, Poole EM, Stampfer M, Tworoger SS, Bandera EV, Orlow I, Olson SH, Bjorge L, Salvesen HB, Van Altena AM, Aben KKH, Kiemeney LA, Massuger LFAG, Pejovic T, Bean Y, Brooks-Wilson A, Kelemen LE, Cook LS, Le ND, Grski B, Gronwald J, Menkiszak J, Hogdall CK, Lundvall L, Nedergaard L, Engelholm SA, Dicks E, Tyrer J, Campbell I, Mcneish I, Paul J, Siddiqui N, Glasspool R, Whittemore AS, Rothstein JH, Mcguire V, Sieh W, Cai H, Shu XO, Teten RT, Sutphen R, Mclaughlin JR, Narod SA, Phelan CM, Monteiro AN, Fenstermacher D, Lin HY, Permuth JB, Sellers TA, Chen YA, Tsai YY, Chen Z, Gentry-Maharaj A, Gayther SA, Ramus SJ, Menon U, Wu AH, Pearce CL, Van Den Berg D, Pike MC, Dansonka-Mieszkowska A, Plisiecka-Halasa J, Moes-Sosnowska J, Kupryjanczyk J, Pharoah PDP, Song H, Winship I, Chenevix-Trench G, Giles GG, Tavtigian SV, Easton DF, Milne RL (2016)
Publication Type: Journal article
Publication year: 2016
Book Volume: 53
Pages Range: 800-811
Journal Issue: 12
DOI: 10.1136/jmedgenet-2016-103839
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.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.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=7.1×10(-5)), PALB2 c.3113G>A OR 4.21 (95% CI 1.84 to 9.60, p=6.9×10(-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.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.
APA:
Southey, M.C., Goldgar, D.E., Winqvist, R., Pylkas, K., Couch, F., Tischkowitz, M.,... Milne, R.L. (2016). PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS. Journal of Medical Genetics, 53(12), 800-811. https://doi.org/10.1136/jmedgenet-2016-103839
MLA:
Southey, Melissa C., et al. "PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS." Journal of Medical Genetics 53.12 (2016): 800-811.
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