Sensitivity to NNKOAc is associated with renal cancer risk.

Abstract

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.

• Authors: Jessica Clague, Lina Shao, Jie Lin, Shine Chang, Yimin Zhu, Wei Wang, Christopher G Wood, Xifeng Wu
• Journal: Carcinogenesis (Carcinogenesis) Vol. 30 Issue 4 Pg. 706-10 (Apr 2009) ISSN: 1460-2180 [Electronic] England
• PMID: 19237609 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Nitrosamines
• Pyridines
• 4-(acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanone

Topics

• Case-Control Studies
• Comet Assay
• DNA Damage (drug effects)
• DNA Repair (genetics)
• Female
• Humans
• Kidney Neoplasms (chemically induced, genetics, pathology)
• Lung Neoplasms (chemically induced, genetics, pathology)
• Lymphocytes (metabolism, pathology)
• Male
• Middle Aged
• Nitrosamines (pharmacology)
• Pyridines (pharmacology)
• Risk Factors
• Smoking