ABSTRACT
BACKGROUND: The combined effects of thoracic radiotherapy (XRT) and cigarette smoking are not known with certainty, but they have important implications for lung carcinogenesis after cancer therapy in some patients. The authors analyzed smoking, radiation, and both exposures on lung carcinoma development in women who were treated previously for breast carcinoma. METHODS: Case patients (n = 280) were female residents of the United States, ages 30-89 years, with breast carcinoma prior to primary lung carcinoma diagnosed between 1960 and 1997. Control patients (n = 300) were selected randomly from 37,000 patients with breast carcinoma who were treated at The University of Texas M. D. Anderson Cancer Center and frequency matched with women in the case group based on age at diagnosis (5-year strata), ethnicity, year of breast carcinoma diagnosis (5-year strata), and survival from breast carcinoma diagnosis to lung carcinoma diagnosis. Using stratified analysis and unconditional logistic regression, the authors evaluated the main and combined effects of smoking and XRT on lung carcinoma risk. RESULTS: At the time of breast carcinoma diagnosis, 84% of case patients had ever smoked cigarettes, compared with 37% of control patients, whereas 45% of case patients and control patients received XRT for breast carcinoma. Smoking increased the odds of lung carcinoma in women without XRT (odds ratio [OR], 6.0; 95% confidence interval [95% CI], 3.6-10.1), but XRT did not increase lung carcinoma risk in nonsmoking women (OR, 0.5; 95% CI, 0.3-1.1). Overall, the OR for both XRT and smoking, compared with no XRT or smoking, was 9.0 (95% CI, 5.1-15.9). Logistic regression modeling yielded an adjusted OR of 5.6 for the smoking main effect (95% CI, 2.9-10.5), 0.6 for the XRT main effect (95% CI, 0.3-1.4), and 8.6 (P = 0.08) for the combined effect. CONCLUSIONS: Smoking was a significant independent risk factor for lung carcinoma after breast carcinoma, but XRT alone was not. Smoking and XRT combined enhanced the effect of either alone, with marked increased risks of lung carcinoma after XRT for breast carcinoma.
Subject(s)
Breast Neoplasms/epidemiology , Breast Neoplasms/radiotherapy , Lung Neoplasms/epidemiology , Neoplasms, Radiation-Induced/epidemiology , Smoking/adverse effects , Adult , Age Distribution , Aged , Aged, 80 and over , Breast Neoplasms/surgery , Case-Control Studies , Confidence Intervals , Female , Humans , Incidence , Lung Neoplasms/etiology , Lung Neoplasms/physiopathology , Mastectomy, Segmental/methods , Middle Aged , Neoplasms, Radiation-Induced/diagnosis , Odds Ratio , Probability , Radiotherapy, Adjuvant/adverse effects , Registries , Retrospective Studies , Risk Assessment , Survival Analysis , United States/epidemiologyABSTRACT
To test the hypothesis that individual susceptibility to carcinogen exposure is a risk factor for breast cancer, we measured DNA adduct formation in normal breast tissues treated in vitro with 4 micro M benzo(a)pyrene in 76 cancer cases and 60 noncancer controls. We found a significantly higher level of adducts (134.6 +/- 21.2/10(9)) among cases compared with controls (66.9 +/- 7.5; P = 0.007). The level of adducts was significantly associated with the risk of breast cancer (odds ratio, 4.38; 95% confidence interval, 1.04 to 18.50; P = 0.044) after adjusting for confounders. Stratified analysis and regression analysis demonstrated that race, pack-years of smoking, family history of breast cancer, and CYP1B1 genotype were significant predictors of the level of benzo(a)pyrene-induced adducts in the breast tissues. These observations suggest that genetic susceptibility to carcinogen exposure may play an important role in breast carcinogenesis.