title: 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.affiliation: Department of Epidemiology, University of Texas M. D. Anderson Cancer Center, 1155 Pressler, unit 1340, Houston, TX 77030, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Clague
authors.forename: Lina
authors.initials: L
authors.lastname: Shao
authors.forename: Jie
authors.initials: J
authors.lastname: Lin
authors.forename: Shine
authors.initials: S
authors.lastname: Chang
authors.forename: Yimin
authors.initials: Y
authors.lastname: Zhu
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Wood
authors.forename: Xifeng
authors.initials: X
authors.lastname: Wu
mesh_terms: D016022:Case-Control Studies; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D004260:DNA Repair / Q000235:genetics; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000139:chemically induced* / Q000235:genetics* / Q000473:pathology; D008175:Lung Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009602:Nitrosamines / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D012307:Risk Factors; D012907:Smoking
chemical_list: D009602:Nitrosamines; D011725:Pyridines; C081510:4-(acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanone