Bulky DNA adducts and risk of cancer: a meta-analysis.

We present a meta-analysis to test the hypothesis that the presence of a high level of bulky DNA adducts in tissues is associated with an increased risk of cancer in humans. Seven articles were selected that matched the selection criteria, for a total of 691 cancer patients and 632 control subjects. In five studies the cases had lung cancer, in one oral cancer, and in one bladder cancer. Six studies measured adducts in WBCs and one in normal lung tissue around tumor tissue. Six were case-control investigations, and one was a case-control study on lung cancer nested within a cohort. Current smokers showed a statistically significant difference between cases and controls, with cases having 83% higher levels of adducts than controls (95% confidence interval, 0.44-1.22). Results were negative or contradictory in ex-smokers and nonsmokers. This observation was confirmed by sensitivity analyses. Publication bias does not seem to be a problem. Despite some methodological limitations, our meta-analysis shows that current smokers with high levels of adducts have an increased risk of lung and bladder cancers. This conclusion also suggests that similar (aromatic) compounds may be involved in the etiology of both types of cancer.

[1]  F P Perera,et al.  Association between carcinogen-DNA adducts in white blood cells and lung cancer risk in the physicians health study. , 2001, Cancer research.

[2]  P Vineis,et al.  XRCC1, XRCC3, XPD gene polymorphisms, smoking and (32)P-DNA adducts in a sample of healthy subjects. , 2001, Carcinogenesis.

[3]  P. Simpson,et al.  Statistical methods in cancer research , 2001, Journal of surgical oncology.

[4]  P Vineis,et al.  Markers of DNA repair and susceptibility to cancer in humans: an epidemiologic review. , 2000, Journal of the National Cancer Institute.

[5]  F. V. van Schooten,et al.  Comparison between smoking-related DNA adduct analysis in induced sputum and peripheral blood lymphocytes. , 2000, Carcinogenesis.

[6]  K. H. Huang,et al.  DNA adduct level in lung tissue may act as a risk biomarker of lung cancer. , 2000, European journal of cancer.

[7]  H. Bartsch.  Studies on biomarkers in cancer etiology and prevention: a summary and challenge of 20 years of interdisciplinary research. , 2000, Mutation research.

[8]  P Vineis,et al.  White blood cell DNA adducts and fruit and vegetable consumption in bladder cancer. , 2000, Carcinogenesis.

[9]  Xifeng Wu,et al.  Analysis of aromatic DNA adducts and 7,8‐dihydro‐8‐oxo‐ 2′‐deoxyguanosine in lymphocyte DNA from a case–control study of lung cancer involving minority populations , 2000, Molecular carcinogenesis.

[10]  D. Phillips,et al.  Standardization and validation of DNA adduct postlabelling methods: report of interlaboratory trials and production of recommended protocols. , 1999, Mutagenesis.

[11]  K. Hemminki,et al.  Hprt mutant frequency and aromatic DNA adduct level in non-smoking and smoking lung cancer patients and population controls. , 1999, Carcinogenesis.

[12]  J Verhaert,et al.  Differences in aromatic-DNA adduct levels between alveolar macrophages and subpopulations of white blood cells from smokers. , 1998, Carcinogenesis.

[13]  S. Nesnow,et al.  Mechanistic relationships between DNA adducts, oncogene mutations, and lung tumorigenesis in strain A mice. , 1998, Experimental lung research.

[14]  F P Perera,et al.  Contribution of genetic and nutritional factors to DNA damage in heavy smokers. , 1997, Carcinogenesis.

[15]  M. Tang,et al.  Preferential Formation of Benzo[a]pyrene Adducts at Lung Cancer Mutational Hotspots in P53 , 1996, Science.

[16]  N Dubin,et al.  Effects of dietary supplementation of alpha-tocopherol on plasma glutathione and DNA repair activities. , 1996, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[17]  F P Perera,et al.  A molecular epidemiological case-control study of lung cancer. , 1995, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[18]  W Popp,et al.  DNA strand breakage and DNA adducts in lymphocytes of oral cancer patients. , 1993, Carcinogenesis.

[19]  N. Laird,et al.  Meta-analysis in clinical trials. , 1986, Controlled clinical trials.

[20]  N. Breslow,et al.  Statistical methods in cancer research: volume 1- The analysis of case-control studies , 1980 .

[21]  N. Breslow,et al.  Statistical methods in cancer research. Vol. 1. The analysis of case-control studies. , 1981 .

[22]  N. Breslow,et al.  The analysis of case-control studies , 1980 .

[23]  H Checkoway,et al.  Bias due to misclassification in the estimation of relative risk. , 1977, American journal of epidemiology.