Separation of initiating and promoting effects of the skin carcinogen 7-bromomethylbenz(a)anthracene

Dibenz(a,c)anthracene and 7-bromomethylbenz(a)-anthracene arehydrocarbons with comparable tumor initiating potencies, althoughthey differ about 100-fold in the amount of hydrocarbon boundto mouse skin DNA. We have found that they are comparably mutagenicin Salmonella typhimurium strain TA 100, but that 7-bromomethylbenz(a)anthraceneis additionally mutagenic in strains TA 1538 and TA 98. Thebromo-compound is also a powerful promoter of tumors initiatedin mouse skin with 7, 12-dimethylbenz(a)anthracene, whereasdibenz-(a, c)anthracene is inactive as a promoter. Accordingly,7-bromomethylbenz(a)anthracene is an effective complete carcinogenin mouse skin, while dibenz(a, c)anthracene is not. These resultssuggest that certain types of chemical damage are far more effectivethan others for initiation, but that extensive non-initiatingdamage may be effective for promotion. This has previously beenproposed for different alkylating agents, which differ in theirabilities to attack DNA and protein, but has not been demonstratedin a single compound. 7-Bromomethylbenz(a)anthracene is foundin this experiment to be the most powerful skin tumor promoterknown outside of the phorbol ester series. It may be concludedfrom these results and others that total binding of carcinogento DNA is not quantitatively related to mutagenic events ortumor initiation, but may be an index of overall risk of tumordevelopment.     

Associations between both genetic and environmental biomarkers and lung cancer: evidence of a greater risk of lung cancer in women smokers

This molecular epidemiologic case-control study of lung cancer incorporated three complementary biomarkers: the glutathione S- transferase M1 (GSTM1) null genotype, a potential marker of susceptibility, and polycyclic aromatic hydrocarbon-DNA adducts (PAH- DNA) and sister chromatid exchanges (SCE), both indicators of environmentally induced genetic damage. Associations between biomarkers and lung cancer were investigated, as were possible gene-environment interactions between the GSTM1 null genotype and tobacco smoke exposure. Subjects included 136 primary non-small cell lung cancer surgical patients and 115 controls at the Columbia Presbyterian Medical Center. Questionnaire and Tumor Registry data, pre-treatment blood samples and biomarker measurements on blood were obtained. Overall, GSTM1 null genotype was significantly associated with lung cancer [odds ratio (OR) = 2.04, 95% confidence interval (CI) = 1.13-3.68]. ORs for GSTM1 and lung cancer were significant in females (2.50, 1.09-5.72) and smokers (2.25, 1.11-4.54) and not significant in males (1.4, 0.58-3.38) and non-smokers (0.88, 0.18-4.33). However, ORs for males versus females and smokers versus non-smokers did not differ significantly. The OR for GSTM1 and lung cancer in female smokers was 3.03 (1.09- 8.40), compared with 1.42 (0.53-4.06) in male smokers. In contrast to PAH-DNA adducts in leukocytes, SCE did not differ between cases and controls. Neither biomarker differed significantly between the two GSTM1 genotypes. The combined effect of elevated PAH-DNA adducts and GSTM1 genotype on case-control status (16.19, 1.2-115) appeared multiplicative. Results suggest that the effect of the GSTM1 null genotype is greatest in female smokers, which is consistent with other evidence that indicates that women are at higher risk of lung cancer than males, given equal smoking. Persons with both the GSTM1 deletion and elevated PAH-DNA adducts may represent a sensitive subpopulation with respect to carcinogens in tobacco smoke and other environmental media.      

Exploring the decision-making preferences of people with colorectal cancer

OBJECTIVES: To explore patient views on participation in treatment, physical care and psychological care decisions and factors that facilitate and hinder patients from making decisions. DESIGN: Qualitative study using semi-structured interviews with patients. SETTING AND PARTICIPANTS: Three NHS Trusts in the north-west of England. Theoretical sampling including 41 patients who had been treated for colorectal cancer. RESULTS: For patients, participation in the decision-making process was about being informed and feeling involved in the consultation process, whether patients actually made decisions or not. The perceived availability of treatment choices (surgery, radiotherapy, chemotherapy) was related to type of treatment. Factors that impacted on whether patients wanted to make decisions included a lack of information, a lack of medical knowledge and trust in medical expertise. Patients perceived that they could have a more participatory role in decisions related to physical and psychological care. CONCLUSION: This study has implications for health professionals aiming to implement policy guidelines that promote patient participation and shared partnerships. Patients in this study wanted to be well informed and involved in the consultation process but did not necessarily want to use the information they received to make decisions. The presentation of choices and preferences for participation may be context specific and it cannot be assumed that patients who do not want to make decisions about one aspect of their care and treatment do not want to make decisions about other aspects of their care and treatment.