BRCA2 Polymorphic Stop Codon K3326X and the Risk of Breast, Prostate, and Ovarian Cancers

• Type: Article in International Scientific Journal
• Date: 2016

Authors

Meeks, HD (Author) Other; Song, HL (Author) Other; Michailidou, K (Author) Other; Bolla, MK (Author) Other; Dennis, J (Author) Other; Wang, Q (Author) Other; Barrowdale, D (Author) Other; Frost, D (Author) Other; McGuffog, L (Author) Other; Ellis, S (Author) Other; Feng, BJ (Author) Other; Buys, SS (Author) Other; Hopper, JL (Author) Other; Southey, MC (Author) Other; Tesoriero, A (Author) Other; James, PA (Author) Other; Bruinsma, F (Author) Other; Campbell, IG (Author) Other; Broeks, A (Author) Other; Schmidt, MK (Author) Other; Hogervorst, FBL (Author) Other; Beckman, MW (Author) Other; Fasching, PA (Author) Other; Fletcher, O (Author) Other; Johnson, N (Author) Other; Sawyer, EJ (Author) Other; Riboli, E (Author) Other; Banerjee, S (Author) Other; Menon, U (Author) Other; Tomlinson, I (Author) Other; Burwinkel, B (Author) Other; Hamann, U (Author) Other; Marme, F (Author) Other; Rudolph, A (Author) Other; Janavicius, R (Author) Other; Tihomirova, L (Author) Other; Tung, N (Author) Other; Garber, J (Author) Other; Cramer, D (Author) Other; Terry, KL (Author) Other; Poole, EM (Author) Other; Tworoger, SS (Author) Other; Dorfling, CM (Author) Other; van Rensburg, EJ (Author) Other; Godwin, AK (Author) Other; Guenel, P (Author) Other; Truong, T (Author) Other; Stoppa Lyonnet, D (Author) Other; Damiola, F (Author) Other; Mazoyer, S (Author) Other; Sinilnikova, OM (Author) Other; Isaacs, C (Author) Other; Maugard, C (Author) Other; Bojesen, SE (Author) Other; Flyger, H (Author) Other; Gerdes, AM (Author) Other; Hansen, TVO (Author) Other; Jensen, A (Author) Other; Kjaer, SK (Author) Other; Hogdall, C (Author) Other; Hogdall, E (Author) Other; Pedersen, IS (Author) Other; Thomassen, M (Author) Other; Benitez, J (Author) Other; Gonzalez Neira, A (Author) Other; Osorio, A (Author) Other; de la Hoya, M (Author) Other; Perez Segura, PP (Author) Other; Diez, O (Author) Other; Lazaro, C (Author) Other; Brunet, J (Author) Other; Anton Culver, H (Author) Other; Eunjung, L (Author) Other; John, EM (Author) Other; Neuhausen, SL (Author) Other; Ding, YC (Author) Other; Castillo, D (Author) Other; Weitzel, JN (Author) Other; Ganz, PA (Author) Other; Nussbaum, RL (Author) Other; Chan, SB (Author) Other; Karlan, BY (Author) Other; Lester, J (Author) Other; Wu, A (Author) Other; Gayther, S (Author) Other; Ramus, SJ (Author) Other; Sieh, W (Author) Other; Whittermore, AS (Author) Other; Monteiro, ANA (Author) Other; Phelan, CM (Author) Other; Terry, MB (Author) Other; Piedmonte, M (Author) Other; Offit, K (Author) Other; Robson, M (Author) Other; Levine, D (Author) Other; Moysich, KB (Author) Other; Cannioto, R (Author) Other; Olson, SH (Author) Other; Daly, MB (Author) Other; Nathanson, KL (Author) Other; Domchek, SM (Author) Other; Lu, KH (Author) Other; Liang, D (Author) Other; Hildebrant, MAT (Author) Other; Ness, R (Author) Other; Modugno, F (Author) Other; Pearce, L (Author) Other; Goodman, MT (Author) Other; Thompson, PJ (Author) Other; Brenner, H (Author) Other; Butterbach, K (Author) Other; Meindl, A (Author) Other; Hahnen, E (Author) Other; Wappenschmidt, B (Author) Other; Brauch, H (Author) Other; Bruening, T (Author) Other; Blomqvist, C (Author) Other; Khan, S (Author) Other; Nevanlinna, H (Author) Other; Pelttari, LM (Author) Other; Aittomaeki, K (Author) Other; Butzow, R (Author) Other; Bogdanova, NV (Author) Other; Doerk, T (Author) Other; Lindblom, A (Author) Other; Margolin, S (Author) Other; Rantala, J (Author) Other; Kosma, VM (Author) Other; Mannermaa, A (Author) Other; Lambrechts, D (Author) Other; Neven, P (Author) Other; Claes, KBM (Author) Other; Van Maerken, T (Author) Other; Chang Claude, J (Author) Other; Flesch Janys, D (Author) Other; Heitz, F (Author) Other; Varon Mateeva, R (Author) Other; Peterlongo, P (Author) Other; Radice, P (Author) Other; Viel, A (Author) Other; Barile, M (Author) Other; Peissel, B (Author) Other; Manoukian, S (Author) Other; Montagna, M (Author) Other; Oliani, C (Author) Other; Peixoto, A (Author) Other; Manuel R Teixeira (Author) ICBAS; Collavoli, A (Author) Other; Hallberg, E (Author) Other; Olson, JE (Author) Other; Goode, EL (Author) Other; Hart, SN (Author) Other; Shimelis, H (Author) Other; Cunningham, JM (Author) Other; Giles, GG (Author) Other; Milne, RL (Author) Other; Healey, S (Author) Other; Tucker, K (Author) Other; Haiman, CA (Author) Other; Henderson, BE (Author) Other; Goldberg, MS (Author) Other; Tischkowitz, M (Author) Other; Simard, J (Author) Other; Soucy, P (Author) Other; Eccles, DM (Author) Other; Le, N (Author) Other; Borresen Dale, AL (Author) Other; Kristensen, V (Author) Other; Salvesen, HB (Author) Other; Bjorge, L (Author) Other; Bandera, EV (Author) Other; Risch, H (Author) Other; Zheng, W (Author) Other; Beeghly Fadiel, A (Author) Other; Cai, H (Author) Other; Pylkas, K (Author) Other; Tollenaar, RAEM (Author) Other; van der Ouweland, AMW (Author) Other; Andrulis, IL (Author) Other; Knight, JA (Author) Other; Narod, S (Author) Other; Devilee, P (Author) Other; Winqvist, R (Author) Other; Figueroa, J (Author) Other; Greene, MH (Author) Other; Mai, PL (Author) Other; Loud, JT (Author) Other; Garcia Closas, M (Author) Other; Schoemaker, MJ (Author) Other; Czene, K (Author) Other; Darabi, H (Author) Other; McNeish, I (Author) Other; Siddiquil, N (Author) Other; Glasspool, R (Author) Other; Kwong, A (Author) Other; Park, SK (Author) Other; Teo, SH (Author) Other; Yoon, SY (Author) Other; Matsuo, K (Author) Other; Hosono, S (Author) Other; Woo, YL (Author) Other; Gao, YT (Author) Other; Foretova, L (Author) Other; Singer, CF (Author) Other; Rappaport Feurhauser, C (Author) Other; Friedman, E (Author) Other; Laitman, Y (Author) Other; Rennert, G (Author) Other; Imyanitov, EN (Author) Other; Hulick, PJ (Author) Other; Olopade, OI (Author) Other; Senter, L (Author) Other; Olah, E (Author) Other; Doherty, JA (Author) Other; Schildkraut, J (Author) Other; Koppert, LB (Author) Other; Kiemeney, LA (Author) Other; Massuger, LFAG (Author) Other; Cook, LS (Author) Other; Pejovic, T (Author) Other; Li, JM (Author) Other; Borg, A (Author) Other; Ofverholm, A (Author) Other; Rossing, MA (Author) Other; Wentzensen, N (Author) Other; Henriksson, K (Author) Other; Cox, A (Author) Other; Cross, SS (Author) Other; Pasini, BJ (Author) Other; Shah, M (Author) Other; Kabisch, M (Author) Other; Torres, D (Author) Other; Jakubowska, A (Author) Other; Lubinski, J (Author) Other; Gronwald, J (Author) Other; Agnarsson, BA (Author) Other; Kupryjanczyk, J (Author) Other; Moes Sosnowska, J (Author) Other; Fostira, F (Author) Other; Konstantopoulou, I (Author) Other; Slager, S (Author) Other; Jones, M (Author) Other; Antoniou, AC (Author) Other; Berchuck, A (Author) Other; Swerdlow, A (Author) Other; Chenevix Trench, G (Author) Other; Dunning, AM (Author) Other; Pharoah, PDP (Author) Other; Hall, P (Author) Other; Easton, DF (Author) Other; Couch, FJ (Author) Other; Spurdle, AB (Author) Other; Goldgar, DE (Author) Other

Journal

Title: Journal of the National Cancer Institute

Vol. 108

ISSN: 0027-8874

Publisher: Oxford University Press

Indexing

ISI Web of Knowledge - 68 Citations

Scopus - 69 Citations

Other information

Authenticus ID: P-00K-7T8

DOI: 10.1093/jnci/djv315

Abstract (EN): Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10(-6)) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10(-3)). These associations were stronger for serous ovarian cancer and for estrogen receptor-negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10(-5) and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10(-5), respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10