): Lung cancer is the leading cause of cancer related deaths among both males and females in the United States. Surgical resection remains the only curative therapy for patients with non-small cell lung cancer (NSCLC). Despite undergoing curative resection, a large percentage of patients (30 to 40%) with stage I (node-negative) NSCLC develop recurrent disease. Improvements in adjuvant therapy and in the ability to identify those patients most likely to benefit from adjuvant therapy are essential to improving survival in patients with NSCLC. The proposed study uses common molecular genetic events in the neoplastic progression of NSCLC to improve the ability to assign pathological stage, determine prognosis, and to detect disease recurrence in patients with early stage disease. The influence of p53 and K-ras gene mutations on disease-free and overall survival will be examined in patients with node-negative NSCLC. Molecular techniques will be used to determine the presence of micrometastatic disease in regional lymph nodes in patients undergoing surgical resection. The influence of micrometastatic disease on clinical outcome will be determined for patients with stage I NSCLC. In addition, tumor-specific p53 and K-ras gene mutations and/or microsatellite alterations will be identified in the serum DNA of patients with early-stage NSCLC and their presence correlated with clinical outcome. Completion of the research project will enable the candidate, an Assistant Professor in General Surgery with a strong interest in surgical oncology, to learn state-of-the-art molecular techniques with previously demonstrated clinical utility in the staging and screening of patients with cancer. The mentor's laboratory is an ideal place to pursue this project having made substantial contributions in this field. In addition, the wider network of investigators in the field of cancer genetics at the candidate's institution provides a constructive setting for critical review and support of ongoing research in this field. Completion of the proposed mentored training period will provide the candidate with an excellent foundation for pursuing his long-term goals in academic surgical oncology.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Clinical Investigator Award (CIA) (K08)
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Study Section
Subcommittee G - Education (NCI)
Program Officer
Myrick, Dorkina C
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Medical College of Wisconsin
Schools of Medicine
United States
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Hu, Ying Chuan; Ahrendt, Steven A (2005) hOGG1 Ser326Cys polymorphism and G:C-to-T:A mutations: no evidence for a role in tobacco-related non small cell lung cancer. Int J Cancer 114:387-93
Casse, Celine; Hu, Ying Chuan; Ahrendt, Steven A (2003) The XRCC1 codon 399 Gln allele is associated with adenine to guanine p53 mutations in non-small cell lung cancer. Mutat Res 528:19-27
Ahrendt, Steven A; Hu, Yingchuan; Buta, Martin et al. (2003) p53 mutations and survival in stage I non-small-cell lung cancer: results of a prospective study. J Natl Cancer Inst 95:961-70
Ahrendt, Steven A; Yang, Stephen C; Wu, Li et al. (2002) Molecular assessment of lymph nodes in patients with resected stage I non-small cell lung cancer: preliminary results of a prospective study. J Thorac Cardiovasc Surg 123:466-73; discussion 473-4
Wolf, P; Hu, Y C; Doffek, K et al. (2001) O(6)-Methylguanine-DNA methyltransferase promoter hypermethylation shifts the p53 mutational spectrum in non-small cell lung cancer. Cancer Res 61:8113-7
Ahrendt, S A; Decker, P A; Alawi, E A et al. (2001) Cigarette smoking is strongly associated with mutation of the K-ras gene in patients with primary adenocarcinoma of the lung. Cancer 92:1525-30
Sanchez-Cespedes, M; Decker, P A; Doffek, K M et al. (2001) Increased loss of chromosome 9p21 but not p16 inactivation in primary non-small cell lung cancer from smokers. Cancer Res 61:2092-6
Ahrendt, S A; Decker, P A; Doffek, K et al. (2000) Microsatellite instability at selected tetranucleotide repeats is associated with p53 mutations in non-small cell lung cancer. Cancer Res 60:2488-91
Ahrendt, S A; Chow, J T; Xu, L H et al. (1999) Molecular detection of tumor cells in bronchoalveolar lavage fluid from patients with early stage lung cancer. J Natl Cancer Inst 91:332-9
Ahrendt, S A; Eisenberger, C F; Yip, L et al. (1999) Chromosome 9p21 loss and p16 inactivation in primary sclerosing cholangitis-associated cholangiocarcinoma. J Surg Res 84:88-93