| Autor: |
Rebbeck, TR, Mitra, N, Wan, F, Sinilnikova, OM, Healey, S, McGuffog, L, Chenevix-Trench, G, Easton, DF, Antoniou, AC, Nathanson, KL, Laitman, Y, Kushnir, A, Paluch-Shimon, S, Berger, R, Zidan, J, Friedman, E, Ehrencrona, H, Stenmark-Askmalm, M, Einbeigi, Z, Loman, N, Harbst, K, Rantala, J, Melin, B, Huo, D, Olopade, OI, Seldon, J, Ganz, PA, Nussbaum, RL, Chan, SB, Odunsi, K, Gayther, SA, Domchek, SM, Arun, BK, Lu, KH, Mitchell, G, Karlan, BY, Walsh, C, Lester, J, Godwin, AK, Pathak, H, Ross, E, Daly, MB, Whittemore, AS, John, EM, Miron, A, Terry, MB, Chung, WK, Goldgar, DE, Buys, SS, Janavičius, R, Tihomirova, L, Tung, N, Dorfling, CM, Van Rensburg, EJ, Steele, L, Neuhausen, SL, Ding, YC, Ejlertsen, B, Gerdes, AM, Hansen, TVO, Ramon Y Cajal, T, Osorio, A, Benitez, J, Godino, J, Tejada, MI, Duran, M, Weitzel, JN, Bobolis, KA, Sand, SR, Fontaine, A, Savarese, A, Pasini, B, Peissel, B, Bonanni, B, Zaffaroni, D, Vignolo-Lutati, F, Scuvera, G, Giannini, G, Bernard, L, Genuardi, M, Radice, P, Dolcetti, R, Manoukian, S, Pensotti, V, Gismondi, V, Yannoukakos, D, Fostira, F, Garber, J, Torres, D, Rashid, MU |
| Jazyk: |
angličtina |
| Rok vydání: |
2015 |
| Předmět: |
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| Zdroj: |
Rebbeck, TR; Mitra, N; Wan, F; Sinilnikova, OM; Healey, S; McGuffog, L; et al.(2015). Association of type and location of BRCA1 and BRCA2 mutations with risk of breast and ovarian cancer. JAMA-Journal of the American Medical Association, 313(13), 1347-1361. doi: 10.1001/jama.2014.5985. UCLA: Retrieved from: http://www.escholarship.org/uc/item/5t19d4b5 |
| DOI: |
10.1001/jama.2014.5985. |
| Popis: |
Importance: Limited information about the relationship between specific mutations in BRCA1 or BRCA2 (BRCA1/2) and cancer risk exists. Objective: To identify mutation-specific cancer risks for carriers of BRCA1/2. Design, Setting, and Participants: Observational study ofwomen whowere ascertained between 1937 and 2011 (median, 1999) and found to carry disease-associated BRCA1 or BRCA2 mutations. The international sample comprised 19 581 carriers of BRCA1 mutations and 11 900 carriers of BRCA2 mutations from 55 centers in 33 countries on 6 continents.We estimated hazard ratios for breast and ovarian cancer based on mutation type, function, and nucleotide position.We also estimated RHR, the ratio of breast vs ovarian cancer hazard ratios. A value of RHR greater than 1 indicated elevated breast cancer risk; a value of RHR less than 1 indicated elevated ovarian cancer risk. Exposures: Mutations of BRCA1 or BRCA2. Main Outcomes and Measures: Breast and ovarian cancer risks. Results: Among BRCA1 mutation carriers, 9052 women (46%) were diagnosed with breast cancer, 2317 (12%) with ovarian cancer, 1041 (5%) with breast and ovarian cancer, and 7171 (37%) without cancer. Among BRCA2 mutation carriers, 6180 women (52%) were diagnosed with breast cancer, 682 (6%) with ovarian cancer, 272 (2%) with breast and ovarian cancer, and 4766 (40%) without cancer. In BRCA1, we identified 3 breast cancer cluster regions (BCCRs) located at c.179 to c.505 (BCCR1; RHR = 1.46; 95%CI, 1.22-1.74; P = 2 × 10-6), c.4328 to c.4945 (BCCR2; RHR = 1.34; 95%CI, 1.01-1.78; P = .04), and c. 5261 to c.5563 (BCCR2', RHR = 1.38; 95%CI, 1.22-1.55; P = 6 × 10-9).We also identified an ovarian cancer cluster region (OCCR) from c.1380 to c.4062 (approximately exon 11) with RHR = 0.62 (95%CI, 0.56-0.70; P = 9 × 10-17). In BRCA2, we observed multiple BCCRs spanning c.1 to c.596 (BCCR1; RHR = 1.71; 95%CI, 1.06-2.78; P = .03), c.772 to c.1806 (BCCR1'; RHR = 1.63; 95%CI, 1.10-2.40; P = .01), and c.7394 to c.8904 (BCCR2; RHR = 2.31; 95%CI, 1.69-3.16; P = .00002).We also identified 3 OCCRs: the first (OCCR1) spanned c.3249 to c.5681 that was adjacent to c.5946delT (6174delT; RHR = 0.51; 95%CI, 0.44-0.60; P = 6 × 10-17). The second OCCR spanned c.6645 to c.7471 (OCCR2; RHR = 0.57; 95%CI, 0.41-0.80; P = .001). Mutations conferring nonsense-mediated decay were associated with differential breast or ovarian cancer risks and an earlier age of breast cancer diagnosis for both BRCA1 and BRCA2 mutation carriers. Conclusions and Relevance: Breast and ovarian cancer risks varied by type and location of BRCA1/2 mutations. With appropriate validation, these data may have implications for risk assessment and cancer prevention decision making for carriers of BRCA1 and BRCA2 mutations. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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