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Carcinogenesis Advance Access published online on February 23, 2009
Carcinogenesis, doi:10.1093/carcin/bgp045
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© The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Sensitivity to NNKOAc is associated with renal cancer risk

Jessica Clague*,1, Lina Shao*,1, Jie Lin1, Shine Chang1, Yimin Zhu1, Wei Wang1, Christopher G Wood2 and Xifeng Wu1

1 Department of Epidemiology
2 Urology, University of Texas M. D. Anderson Cancer Center, 1155 Pressler, Box 1340, Houston, TX 77030

Correspondence to: Xifeng Wu, Department of Epidemiology, Box 1340, The University of Texas M. D. Anderson Cancer Center, 1155 Pressler, Houston, TX 77030. Tel: 713-745-2485; Fax: 713-792-4657. Email: xwu{at}mdanderson.org

Cigarette smoking has been investigated as a major risk factor for renal cell carcinoma (RCC). The 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is one of the most abundant carcinogenic N-nitrosamines present in cigarette smoke. However, the association between repair capacity of NNK-induced DNA damage and RCC risk remains unknown. We used the comet assay to assess whether sensitivity to a NNK precursor 4-[(acetoxymethyl) nitrosamino]-1-(3-pyridyl)-1-butanone (NNKOAc) induced DNA damage, which partly reflects host sensitivity to NNK, was associated with increased risk of RCC in a population-based case-control study. The study included 95 RCC cases and 188 matched controls. Epidemiologic data were collected via in-person interview. Baseline and NNK-induced DNA damage in peripheral blood lymphocytes were measured using the comet assay and quantified by the Olive tail moment. The NNKOAc-induced median Olive tail moments were significantly higher in cases than in controls (2.27 vs 1.76, P=0.002). Using the 75th percentile Olive tail moments of the controls as the cutoff point, we found that higher levels of NNKOAc-induced DNA damage were associated with a significantly increased risk of RCC [Odds Ratio (OR), 2.06; 95% Confidence Interval (95%CI), 1.17-3.61]. In quartile analysis, there was a dose-response association between NNKOAc-induced damage and risk of RCC (P for trend, 0.006). Our data strongly suggest that higher levels of NNKOAc-induced damage are associated with higher risks of RCC. Future studies with larger sample sizes are warranted to further investigate whether repair of NNKOAc-induced damage, as quantified by the comet assay, could be used as a predictive marker for RCC risk.

* JC and LS contributed equally to the manuscript.

Received November 6, 2008; revised February 10, 2009; accepted February 14, 2009.


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