Gefitinib, an epidermal growth factor receptor blockade agent, shows additional or synergistic effects on the radiosensitivity of esophageal cancer cells in vitro.

Human esophageal cancers have been shown to express high levels of epidermal growth factor receptor (EGFR) and a relationship between high EGFR expression and local advance, the number of lymph node metastases, life expectancy, and sensitivity to chemo-radiotherapy has been demonstrated. We examined the use of gefitinib, an orally active EGFR-selective tyrosine kinase inhibitor, as a new strategy for treatment of esophageal carcinoma. The effects of gefitinib were evaluated in monotherapy and in combination with radiotherapy in human esophageal carcinoma cell lines. Gefitinib produced a dose-dependent inhibition of cellular proliferation in all of the 8 esophageal carcinoma cell lines examined, with IC50 values ranging from 5.7 microM to 36.9 microM. In combination, gefitinib and radiotherapy showed a synergistic effect in 2 human esophageal carcinoma cell lines and an additive effect in 5 cell lines. Western blotting demonstrated that gefitinib blocked activation of the EGFR-extracellular signal-regulated kinase (Erk) pathway and the EGFR-phosphoinositide-3 kinase (PI3K)-Akt pathway after irradiation. These results suggest that further evaluation of EGFR blockade as a treatment for esophageal cancer should be performed, and that radiotherapy combined with EGFR blockade may enhance the response of esophageal carcinoma to therapy.</p

Association between Mammographic Breast Density and Lifestyle in Japanese Women

A high mammographic breast density is considered to be a risk factor for breast cancer. However, only a small number of studies on the association between breast density and lifestyle have been performed. A cross-sectional study was performed using a survey with 29 questions on life history and lifestyle. The breast density on mammography was classified into 4 categories following the BI-RADS criteria. The subjects were 522 women with no medical history of breast cancer. The mean age was 53.3 years old. On multivariate analysis, only BMI was a significant factor determining breast density in premenopausal women (parameter estimate, －0.403;p value, 0.0005), and the density decreased as BMI rose. In postmenopausal women, BMI (parameter estimate, －0.196;p value, 0.0143) and number of deliveries (parameter estimate, －0.388;p value, 0.0186) were significant factors determining breast density;breast density decreased as BMI and number of deliveries increased. Only BMI and number of deliveries were identified as factors significantly influencing breast density. BMI was inversely correlated with breast density before and after menopause, whereas the influence of number of deliveries on breast density was significant only in postmenopausal women in their 50 and 60s

Effects of lifestyle and single nucleotide polymorphisms on breast cancer risk: a case-control study in Japanese women

Background: Lifestyle factors, including food and nutrition, physical activity, body composition and reproductive factors, and single nucleotide polymorphisms (SNPs) are associated with breast cancer risk, but few studies of these factors have been performed in the Japanese population. Thus, the goals of this study were to validate the association between reported SNPs and breast cancer risk in the Japanese population and to evaluate the effects of SNP genotypes and lifestyle factors on breast cancer risk. Methods: A case-control study in 472 patients and 464 controls was conducted from December 2010 to November 2011. Lifestyle was examined using a self-administered questionnaire. We analyzed 16 breast cancer-associated SNPs based on previous GWAS or candidate-gene association studies. Age or multivariate-adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were estimated from logistic regression analyses. Results: High BMI and current or former smoking were significantly associated with an increased breast cancer risk, while intake of meat, mushrooms, yellow and green vegetables, coffee, and green tea, current leisure-time exercise, and education were significantly associated with a decreased risk. Three SNPs were significantly associated with a breast cancer risk in multivariate analysis: rs2046210 (per allele OR = 1.37 [95% CI: 1.11-1.70]), rs3757318 (OR = 1.33[1.05-1.69]), and rs3803662 (OR = 1.28 [1.07-1.55]). In 2046210 risk allele carriers, leisure-time exercise was associated with a significantly decreased risk for breast cancer, whereas current smoking and high BMI were associated with a significantly decreased risk in non-risk allele carriers. Conclusion: In Japanese women, rs2046210 and 3757318 located near the ESR1 gene are associated with a risk of breast cancer, as in other Asian women. However, our findings suggest that exercise can decrease this risk in allele carriers