Prospective analysis of DNA damage and repair markers of lung cancer risk from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial

Mutagen challenge and DNA repair assays have been used in case-control studies for nearly three decades to assess human cancer risk. The findings still engender controversy because blood was drawn after cancer diagnosis so the results may be biased, a type called 'reverse causation'. We therefore used Epstein-Barr virus-transformed lymphoblastoid cell lines established from prospectively collected peripheral blood samples to evaluate lung cancer risk in relation to three DNA repair assays: alkaline Comet assay, host cell reactivation (HCR) assay with the mutagen benzo[a]pyrene diol epoxide and the bleomycin mutagen sensitivity assay. Cases (n = 117) were diagnosed with lung cancer between 0.3 and 6 years after blood collection and controls (n = 117) were frequency matched on calendar year and age at blood collection, gender and smoking history; all races were included. Case and control status was unknown to laboratory investigators. In unconditional logistic regression analyses, statistically significantly increased lung cancer odds ratios (OR(adjusted)) were observed for bleomycin mutagen sensitivity as quartiles of chromatid breaks/cell [relative to the lowest quartile, OR = 1.2, 95% confidence interval (CI): 0.5-2.5; OR = 1.4, 95% CI: 0.7-3.1; OR = 2.1, 95% CI: 1.0-4.4, respectively, P(trend) = 0.04]. The magnitude of the association between the bleomycin assay and lung cancer risk was modest compared with those reported in previous lung cancer studies but was strengthened when we included only incident cases diagnosed more than a year after blood collection (P(trend) = 0.02), supporting the notion the assay may be a measure of cancer susceptibility. The Comet and HCR assays were unrelated to lung cancer risk.     

Regional infusion for colorectal hepatic metastases. A randomized trial comparing the hepatic artery with the portal vein

To evaluate which site of infusion maximizes tumor response to regional hepatic chemotherapy, 25 patients were randomized preoperatively to receive chemotherapy administration via hepatic artery or portal vein catheters. Of the 25 patients, five did not have catheters placed due to extrahepatic disease, and one patient did not receive infusion chemotherapy. Continuous floxuridine infusion was given at a dosage of 0.3 mg/kg/d, alternating with saline solution every two weeks. The mean percentage of hepatic tumor replacement (36% vs 41%), mean serum alkaline phosphatase level (218 vs 179 IU/mL), and mean plasma carcinoembryonic antigen level (689 vs 563 ng/mL) were similar in both groups. Four (50%) of eight hepatic artery patients responded to treatment compared with 0/11 portal vein patients. Ten of 11 portal vein patients showed progressive tumor growth; nine of these patients were crossed over to arterial infusion. Three (33%) of these nine patients had an objective tumor response with the hepatic arterial infusion. This prospective, randomized clinical trial demonstrates significantly improved tumor response after hepatic arterial infusion compared with portal vein infusion.     

A systematic review of the evidence for Canada's Physical Activity Guidelines for Adults

This systematic review examines critically the scientific basis for Canada's Physical Activity Guide for Healthy Active Living for adults. Particular reference is given to the dose-response relationship between physical activity and premature all-cause mortality and seven chronic diseases (cardiovascular disease, stroke, hypertension, colon cancer, breast cancer, type 2 diabetes (diabetes mellitus) and osteoporosis). The strength of the relationship between physical activity and specific health outcomes is evaluated critically. Literature was obtained through searching electronic databases (e.g., MEDLINE, EMBASE), cross-referencing, and through the authors' knowledge of the area. For inclusion in our systematic review articles must have at least 3 levels of physical activity and the concomitant risk for each chronic disease. The quality of included studies was appraised using a modified Downs and Black tool. Through this search we identified a total of 254 articles that met the eligibility criteria related to premature all-cause mortality (N = 70), cardiovascular disease (N = 49), stroke (N = 25), hypertension (N = 12), colon cancer (N = 33), breast cancer (N = 43), type 2 diabetes (N = 20), and osteoporosis (N = 2). Overall, the current literature supports clearly the dose-response relationship between physical activity and the seven chronic conditions identified. Moreover, higher levels of physical activity reduce the risk for premature all-cause mortality. The current Canadian guidelines appear to be appropriate to reduce the risk for the seven chronic conditions identified above and all-cause mortality.     

Human epidermal growth factor receptor 2 oncoprotein expression in breast cancer patients from central Anatolia, Turkey

Aim:   Human epidermal growth factor receptor 2 (HER2) overexpression is associated with poor prognosis and the frequency of HER2 positivity in breast cancer patients varies among different regions of the world. We studied HER2 expression in Turkish breast cancer patients.
Methods:   HER 2 expression was evaluated immunohistochemically in 107 breast cancer patients. HER2 expression was reported as negative or positive (3+) according to cellular membrane staining characteristics. The frequency of HER2 overexpression, distribution according to clinical characteristics, effect on survival and effect of chemotherapy on survival in relation to HER2 overexpression was evaluated.
Results:   The median age of patients was 49 years (range 27–76). HER2 was 3+ in 34 patients (31.8%). There was no significant difference in age, menopausal status, histopathology, lymph node involvement, stage and estrogen and/or progesterone receptor positivity in relation to HER2 expression. Forty-three patients (40.2%) relapsed and 21 patients (19.6%) died during the follow-up period. There was no significant difference in the relapse rate, distribution of relapse sites and death rate in relation to HER2 expression. The 3- and 5-year disease free survival rates were 67.1 and 40.5%, and the overall survival rates were 87.5 and 66.1%, respectively. Survival rate and calculated survival time were relatively shorter in HER2 3+ patients than in non-HER2 3+ patients, but these differences were not statistically significant. HER2 status did not affect survival period according to chemotherapy group.
Conclusion:   Immunohistochemistry findings of HER2 expression in Turkish breast cancer patients were similar to those found in the published reports. A shorter survival period was observed in HER2 3+ patients, but the difference was not statistically significant.     

Polymorphisms in DNA repair genes, ionizing radiation exposure and risk of breast cancer in U.S. Radiologic technologists

High-dose ionizing radiation exposure to the breast and rare autosomal dominant genes have been linked with increased breast cancer risk, but the role of low-to-moderate doses from protracted radiation exposure in breast cancer risk and its potential modification by polymorphisms in DNA repair genes has not been previously investigated among large numbers of radiation-exposed women with detailed exposure data. Using carefully reconstructed estimates of cumulative breast doses from occupational and personal diagnostic ionizing radiation, we investigated the potential modification of radiation-related breast cancer risk by 55 candidate single nucleotide polymorphisms in 17 genes involved in base excision or DNA double-strand break repair among 859 cases and 1083 controls from the United States Radiologic Technologists (USRT) cohort. In multivariable analyses, WRN V114I (rs2230009) significantly modified the association between cumulative occupational breast dose and risk of breast cancer (adjusted for personal diagnostic exposure) (p = 0.04) and BRCA1 D652N (rs4986850), PRKDC IVS15 + 6C > T (rs1231202), PRKDC IVS34 + 39T > C (rs8178097) and PRKDC IVS31 - 634C > A (rs10109984) significantly altered the personal diagnostic radiation exposure-response relationship (adjusted for occupational dose) (p < or = 0.05). None of the remaining 50 SNPs significantly modified breast cancer radiation dose-response relationships. The USRT genetic study provided a unique opportunity to examine the joint effects of common genetic variation and ionizing radiation exposure on breast cancer risk using detailed occupational and personal diagnostic exposure data. The suggestive evidence found for modification of radiation-related breast cancer risk for 5 of the 55 SNPs evaluated requires confirmation in larger studies of women with quantified radiation breast doses in the low-to-moderate range.