Infertility as a risk factor for breast cancer: Results from a hospital-based case–control study

Context: Breast cancer is the most common cancer in women worldwide and its prevalence is increasing. Aims: The aim of this study was to investigate the extent to which a history of infertility can present as risk factors for breast cancer. Settings and Design: This was a hospital-based case–control study. Subjects and Methods: In this study, 1177 women with breast cancer were participated for assessing the risk for this cancer. The control was 1204 women with self-reported free-cancer history who were matched in terms of age and residence. Statistical Analysis Used: Using logistic regression, it was examined whether infertility is a risk factor of case–control status in addition to marriage age, menarche age, body mass index, number of pregnancies, family history of breast cancer, and previous oral contraceptive use. The data were considered significant at P ≤ 0.05. Results: Infertility history was reported in 12.5% (n = 147) of the cases and 5.8% (n = 70) of the controls. Infertility history was a relevant risk for case–control study in addition to other risk factors (odds ratio: 2.43; 95% confidence interval, 3.34–1.77). Conclusions: This study found that infertility may be as the main risk factor for breast cancer in Iranian women, therefore, doing breast screening in women who have one or more risk factors, must receive more emphasis

Regulation of HSVtk gene by endogenous microRNA-122a in liver cell lines as suicide gene therapy

Aim: Here, we use miR-122a that exhibits liver-specific expression for developing a post-transcriptional regulative system mediated by microRNAs

Background: Gene therapy with adenovirus [Ad] vectors that express herpes simplex virus thymidine kinase [HSVtk] and ganciclovir [GCV] have been suggested as a therapeutic strategy to cancer. However, Ad vectors injected into tumors are dispersed into the systemic circulation and transduce liver cells, resulting in severe hepatotoxicity. To be effective, the delivery and expression of suicide genes to cancer treatment ought to be specific to tumor cells, and avoid death of healthy cells. Researchers have demonstrated that expression of transgene could be suppressed in healthy cells with use of vectors that are reactive to microRNA regulation

Methods: We constructed an Ad vector carrying four tandem copies of target sequences of miR-122a that were incorporated into 3'- UTR of HSVtk gene. The expression level of miR-122a was quantified in HepG2 and Huh7 cell lines

Results: Quantitative RT- PCR analysis demonstrated that Huh7 cells express large amounts of miR-122a compared to HepG2 cells. The viability of Huh7 cells and HepG2 cells after infection by Ad-tk-122aT vector was 83% and 23.5%, respectively. The viability of Huh7 cells was not reduced in the presence of GCV after infection by Ad-tk-122a vector. In contrast, cytotoxicity of HSV-tk/GCV was similar in Huh7 cells and HepG2 cells by Ad-tk vector, with 35.3% and 27% viability, respectively

Conclusion: Inclusion of the miR-122a target sequences in the HSVtk expression cassette yielded a feasible strategy for reducing cytotoxicity of suicide gene in a liver cell line with high miR-122a expression