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Human Molecular Genetics Advance Access originally published online on August 18, 2004
Human Molecular Genetics 2004 13(20):2443-2449; doi:10.1093/hmg/ddh260
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Human Molecular Genetics, Vol. 13, No. 20 © Oxford University Press 2004; all rights reserved

BRCA1 mRNA expression levels as an indicator of chemoresistance in lung cancer

Miquel Taron1, Rafael Rosell1,*, Enriqueta Felip2, Pedro Mendez1, John Souglakos5, Maria Sanchez Ronco6, Cristina Queralt1, Joaquim Majo3, Jose Miguel Sanchez1, Jose Javier Sanchez6 and Jose Maestre4

1Medical Oncology Service, Institut Catala d'Oncologia, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain, 2Medical Oncology Service, 3Pathology Department and 4Department of Thoracic Surgery, Hospital Vall d'Hebron, Barcelona, Spain, 5Department of Medical Oncology, General Hospital of Heraklion, Crete, Greece and 6Autonomous University of Madrid, Madrid, Spain

Received April 27, 2004; Revised July 15, 2004; Accepted August 4, 2004

Lung cancer is the most common cancer, with dismal outcome. Treatment approaches, including cisplatin-based chemotherapy and surgery, are currently based on the clinical classification of the tumor, without genetic assessment for predicting differential chemosensitivity. BRCA1 plays a central role in DNA repair, and decreased BRCA1 mRNA expression in the human breast cancer HCC1937 cell line caused cisplatin hypersensitivity, but the relation between BRCA1 and survival in lung cancer patients has never been examined. We used real-time quantitative polymerase chain reaction to determine BRCA1 mRNA levels in 55 surgically resected tumors of non-small-cell lung cancer patients who had received neoadjuvant gemcitabine/cisplatin chemotherapy, and divided the gene expression values into quartiles. When results were correlated with outcome, two cut-offs were observed; patients with levels <0.61 had better outcome, and those >2.45 had poorer outcome. Median survival was not reached for the 15 patients in the bottom quartile, whereas for the 28 in the two middle quartiles, it was 37.8 months (95% CI, 10.6–65), and for the 12 patients in the top quartile, it was 12.7 months (95% CI, 0.28–28.8) (P=0.01). Moreover, when patients were stratified by pathologic stage, those in the bottom quartile had a decreased risk of death (HR=0.206; 95% CI, 0.05–0.83; P=0.026) compared with those in the top quartile, and those in the two middle quartiles also had a decreased risk of death (HR=0.294; 95% CI, 0.10–0.83; P=0.020) compared with those in the top quartile. BRCA1 expression is potentially an important tool for use in cancer management and should be assessed for predicting differential chemosensitivity and tailoring chemotherapy in lung cancer.

* To whom correspondence should be addressed at: Medical Oncology Service, Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Ctra Canyet, s/n, 08916 Badalona, Barcelona, Spain. Tel: +34 934978925; Fax: +34 934978950; Email: rrosell{at}ns.hugtip.scs.es


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