| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Clinical Investigations |
Cancer Research United Kingdom Genetic Epidemiology Group [E. L. G., D. F. E.], Cancer Research Human Cancer Genetics Group, Department of Oncology [A. M. D., B. K., C. S. H., B. A. J. P., P. P. D. P.], and Department of Public Heath and Primary Care [N. E. D.], University of Cambridge, Cambridge CB1 8RN, United Kingdom, and Cancer Prevention Research Program, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109 [E. L. G.]
Somatic genetic alterations in tumors are known to correlate with survival, but little is known about the prognostic significance of germ-line variation. We assessed the effect of germ-line variation on survival among women with breast cancer participating in a British population-based study. Up to 2430 cases for whom current vital status data were available were screened for BRCA1/2 mutations and genotyped for polymorphisms in 22 DNA repair, hormone metabolism, carcinogen metabolism, and other genes. The effect of genotype on outcome was assessed by Cox regression analysis. The largest effect was observed for the silent polymorphism D501D (t>c) in LIG4, a gene involved in DNA double-strand break repair. The estimated hazard ratio (HR) in cc homozygotes relative to tt homozygotes was 4.0 (95% confidence interval, 2.1–7.7; P = 0.002), and this effect remained after stratification by stage, grade, and tumor type [HR, 4.2 (1.8–9.4); P = 0.01]. Total length of a CYP19 IVS4 (ttta)n repeat was also associated with survival [HR, 0.9 (0.8–1.0); P = 0.01], but this became nonsignificant after stratification by stage, grade, and tumor type. Poorer survival was observed for 10 BRCA1 mutation carriers [HR, 4.1 (1.3–13); P = 0.047]; however, after adjustment for known prognostic factors, the HR estimate decreased to 2.0 and became nonsignificant (P = 0.4). CYP17 (P = 0.05) and TP53 (P = 0.06) polymorphisms showed marginally significant associations in unstratified analyses. No effect on survival was seen for polymorphisms in ATM, BRCA1/2, CHK2, KU70, NBS1, RAD51, RAD52, XRCC3, AR, COMT, NQO1, VDR, ADH3, CYP1A1, GSTP1, TGF-ß, or CDH1. Even if confirmed, the prognostic markers identified in this study are unlikely to replace current markers of prognosis such as estrogen receptor status. However, our results demonstrate the potential of the analysis of germ-line variation to provide insight into the biological determinants of response to treatment and prognosis in breast cancer.
This article has been cited by other articles:
|
|
 |
|
  D. Li, H. Suzuki, B. Liu, J. Morris, J. Liu, T. Okazaki, Y. Li, P. Chang, and J. L. Abbruzzese DNA Repair Gene Polymorphisms and Risk of Pancreatic Cancer Clin. Cancer Res., January 15, 2009; 15(2): 740 - 746. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Pooley, C. Baynes, K. E. Driver, J. Tyrer, E. M. Azzato, P. D.P. Pharoah, D. F. Easton, B. A.J. Ponder, and A. M. Dunning Common Single-Nucleotide Polymorphisms in DNA Double-Strand Break Repair Genes and Breast Cancer Risk Cancer Epidemiol. Biomarkers Prev., December 1, 2008; 17(12): 3482 - 3489. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Machella, M. B. Terry, J. Zipprich, I. Gurvich, Y. Liao, R. T. Senie, D. O. Kennedy, and R. M. Santella Double-strand breaks repair in lymphoblastoid cell lines from sisters discordant for breast cancer from the New York site of the BCFR Carcinogenesis, July 1, 2008; 29(7): 1367 - 1372. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-S. Huang, S.-H. Kuo, H.-C. Lien, S.-Y. Yang, S.-L. You, C.-Y. Shen, C.-H. Lin, Y.-S. Lu, and K.-J. Chang The CYP19 TTTA Repeat Polymorphism Is Related to the Prognosis of Premenopausal Stage I-II and Operable Stage III Breast Cancers Oncologist, July 1, 2008; 13(7): 751 - 760. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Leng, C. A. Stidley, R. Willink, A. Bernauer, K. Do, M. A. Picchi, X. Sheng, M. A. Frasco, D. Van Den Berg, F. D. Gilliland, et al. Double-Strand Break Damage and Associated DNA Repair Genes Predispose Smokers to Gene Methylation Cancer Res., April 15, 2008; 68(8): 3049 - 3056. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Okazaki, L. Jiao, P. Chang, D. B. Evans, J. L. Abbruzzese, and D. Li Single-Nucleotide Polymorphisms of DNA Damage Response Genes Are Associated with Overall Survival in Patients with Pancreatic Cancer Clin. Cancer Res., April 1, 2008; 14(7): 2042 - 2048. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Udler, A.-T. Maia, A. Cebrian, C. Brown, D. Greenberg, M. Shah, C. Caldas, A. Dunning, D. Easton, B. Ponder, et al. Common Germline Genetic Variation in Antioxidant Defense Genes and Survival After Diagnosis of Breast Cancer J. Clin. Oncol., July 20, 2007; 25(21): 3015 - 3023. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Rennert, S. Bisland-Naggan, O. Barnett-Griness, N. Bar-Joseph, S. Zhang, H. S. Rennert, and S. A. Narod Clinical Outcomes of Breast Cancer in Carriers of BRCA1 and BRCA2 Mutations N. Engl. J. Med., July 12, 2007; 357(2): 115 - 123. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-R. Long, N. Kataoka, X.-O. Shu, W. Wen, Y.-T. Gao, Q. Cai, and W. Zheng Genetic Polymorphisms of the CYP19A1 Gene and Breast Cancer Survival. Cancer Epidemiol. Biomarkers Prev., November 1, 2006; 15(11): 2115 - 2122. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. T. M. Brekelmans, C. Seynaeve, M. Menke-Pluymers, H. T. Bruggenwirth, M. M. A. Tilanus-Linthorst, C. C. M. Bartels, M. Kriege, A. N. van Geel, C. M. G. Crepin, J. C. Blom, et al. Survival and prognostic factors in BRCA1-associated breast cancer Ann. Onc., March 1, 2006; 17(3): 391 - 400. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Tommiska, H. Eerola, M. Heinonen, L. Salonen, M. Kaare, J. Tallila, A. Ristimaki, K. von Smitten, K. Aittomaki, P. Heikkila, et al. Breast Cancer Patients with p53 Pro72 Homozygous Genotype Have a Poorer Survival Clin. Cancer Res., July 15, 2005; 11(14): 5098 - 5103. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. F. Masson, L. Sharp, S. C. Cotton, and J. Little Cytochrome P-450 1A1 Gene Polymorphisms and Risk of Breast Cancer: A HuGE Review Am. J. Epidemiol., May 15, 2005; 161(10): 901 - 915. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G H de Bock, M Schutte, E M M Krol-Warmerdam, C Seynaeve, J Blom, C T M Brekelmans, H Meijers-Heijboer, C J van Asperen, C J Cornelisse, P Devilee, et al. Tumour characteristics and prognosis of breast cancer patients carrying the germline CHEK2*1100delC variant J. Med. Genet., October 1, 2004; 41(10): 731 - 735. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Seedhouse, R. Faulkner, N. Ashraf, E. Das-Gupta, and N. Russell Polymorphisms in Genes Involved in Homologous Recombination Repair Interact to Increase the Risk of Developing Acute Myeloid Leukemia Clin. Cancer Res., April 15, 2004; 10(8): 2675 - 2680. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Listgarten, S. Damaraju, B. Poulin, L. Cook, J. Dufour, A. Driga, J. Mackey, D. Wishart, R. Greiner, and B. Zanke Predictive Models for Breast Cancer Susceptibility from Multiple Single Nucleotide Polymorphisms Clin. Cancer Res., April 15, 2004; 10(8): 2725 - 2737. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-O. Shu, Y.-T. Gao, Q. Cai, L. Pierce, H. Cai, Z.-X. Ruan, G. Yang, F. Jin, and W. Zheng Genetic Polymorphisms in the TGF-{beta}1 Gene and Breast Cancer Survival: A Report from the Shanghai Breast Cancer Study Cancer Res., February 1, 2004; 64(3): 836 - 839. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Angele, P. Romestaing, N. Moullan, M. Vuillaume, B. Chapot, M. Friesen, W. Jongmans, D. G. Cox, P. Pisani, J.-P. Gerard, et al. ATMHaplotypes and Cellular Response to DNA Damage: Association with Breast Cancer Risk and Clinical Radiosensitivity Cancer Res., December 15, 2003; 63(24): 8717 - 8725. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. P. Medina, S. A. Ahrendt, M. Pollan, P. Fernandez, D. Sidransky, and M. Sanchez-Cespedes Screening of Homologous Recombination Gene Polymorphisms in Lung Cancer Patients Reveals an Association of the NBS1-185Gln Variant and p53 Gene Mutations Cancer Epidemiol. Biomarkers Prev., August 1, 2003; 12(8): 699 - 704. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Kuschel, A. Auranen, C. S. Gregory, N. E. Day, D. F. Easton, B. A. J. Ponder, A. M. Dunning, and P. D. P. Pharoah Common Polymorphisms in Checkpoint Kinase 2 Are not Associated with Breast Cancer Risk Cancer Epidemiol. Biomarkers Prev., August 1, 2003; 12(8): 809 - 812. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Wooster and B. L. Weber Breast and Ovarian Cancer N. Engl. J. Med., June 5, 2003; 348(23): 2339 - 2347. [Full Text] [PDF]
|
|
|
|
|
|
M. Ishitobi, Y. Miyoshi, A. Ando, S. Hasegawa, C. Egawa, Y. Tamaki, M. Monden, and S. Noguchi Association of BRCA2 Polymorphism at Codon 784 (Met/Val) with Breast Cancer Risk and Prognosis Clin. Cancer Res., April 1, 2003; 9(4): 1376 - 1380. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. L. Goode, C. M. Ulrich, and J. D. Potter Polymorphisms in DNA Repair Genes and Associations with Cancer Risk Cancer Epidemiol. Biomarkers Prev., December 1, 2002; 11(12): 1513 - 1530. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Burke and M. A. Austin Genetic Risk in Context: Calculating the Penetrance of BRCA1 and BRCA2 Mutations J Natl Cancer Inst, August 21, 2002; 94(16): 1185 - 1187. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
