Carcinogenesis Advance Access originally published online on February 23, 2009
Carcinogenesis 2009 30(4):706-710; doi:10.1093/carcin/bgp045
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Sensitivity to NNKOAc is associated with renal cancer risk
1 Department of Epidemiology
2 Department of Urology, University of Texas M. D. Anderson Cancer Center, 1155 Pressler, unit 1340, Houston, TX 77030, USA
* To whom correspondence should be addressed. 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). 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 versus 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, 2.06; 95% confidence interval, 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.
Abbreviations: BMI, body mass index; CI, confidence interval; NNK, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone; NNKOAc, 4-[(acetoxymethyl) nitrosamino]-1-(3-pyridyl)-1-butanone; OR, odds ratio; RCC, renal cell carcinoma; XP, xeroderma pigmentosum
These authors contributed equally to this work. Received November 6, 2008; revised February 10, 2009; accepted February 14, 2009.