Carcinogenesis Advance Access published online on September 3, 2004
Carcinogenesis, doi:10.1093/carcin/bgh275
© 2004 by Oxford University Press
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1 EMI INSERM 03-37 and Service d'Urologie, Université Paris XII, AP-HP, Hôpital Henri Mondor, 94000 Créteil - France
* To whom correspondence should be addressed.
Smoking is a major risk factor for urothelial cell carcinoma (UCC) of the bladder. Mutations in FGFR3 and TP53 have been shown to define two distinct pathways in superficial papillary and invasive UCC disease, respectively. We investigated the relationship between smoking and these mutations by means of Denaturing High Performance Liquid Chromatography and sequencing for 110 primary UCC of the bladder. This study included 48 current smokers, 31 ex-smokers and 31 non-smokers. Thirty-five of the tumors were of stage pTa, 40 pT1 and 35 Smoking was associated with high-stage (p=0.03) and high-grade tumors (p=0.006). Twenty-two of the 110 tumors studied harbored TP53 mutations (20%) and 43 harbored FGFR3 mutations (39%). Odds ratios were higher for TP53 mutations in current smokers (OR, 2.25; 95% CI, 0.65-7.75) and ex-smokers (OR, 1.62; 95% CI, 0.41-6.42) than in non-smokers. Double TP53 mutations and A:T>G:C TP53 mutation patterns were found only in current smokers. Patients with the FGFR3wildtype/TP53mutated genotype had significantly higher levels of tobacco consumption, as measured in pack-years (p=0.01). Smoking influenced neither the frequency nor the pattern of FGFR3 mutations. Our results suggest that smoking is associated with invasive and high-grade UCCs, at initial presentation, and influenced TP53 or the molecular pathway defined by these mutations. In contrast, FGFR3 mutations are not affected by smoking and probably result from endogenous alterations. These data have potential implications for clinical management and prevention strategies.
Revised August 20, 2004
Accepted August 24, 2004
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Mutations in TP53, but not FGFR3, in urothelial cell carcinoma of the bladder are influenced by smoking: contribution of exogenous versus endogenous carcinogens
2 Department of Epidemiology, UCLA School of Public Health, Los Angeles, CA 90095-1772, USA
3 Service D'Urologie CHRU Besançon - France
4 UMR-144, CNRS - Institut Curie, 75005 Paris - France
Abstract 
pT2. Fourteen of the tumors were grade 1, 37 were grade 2 and 59 grade 3.
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