Parity and breast cancer risk among BRCA1 and BRCA2 mutation carriers

Introduction

Increasing parity and age at first full-term pregnancy are established risk factors for breast cancer in the general population. However, their effects among BRCA1 and BRCA2 mutation carriers is still under debate. We used retrospective data on BRCA1 and BRCA2 mutation carriers from the UK to assess the effects of parity-related variables on breast cancer risk.

Methods

The data set included 457 mutation carriers who developed breast cancer (cases) and 332 healthy mutation carriers (controls), ascertained through families seen in genetic clinics. Hazard ratios were estimated by using a weighted cohort approach.

Results

Parous BRCA1 and BRCA2 mutation carriers were at a significantly lower risk of developing breast cancer (hazard ratio 0.54, 95% confidence interval 0.37 to 0.81; p = 0.002). The protective effect was observed only among carriers who were older than 40 years. Increasing age at first live birth was associated with an increased breast cancer risk among BRCA2 mutation carriers (p trend = 0.002) but not BRCA1 carriers. However, the analysis by age at first live birth was based on small numbers.

Conclusion

The results suggest that the relative risks of breast cancer associated with parity among BRCA1 and BRCA2 mutation carriers may be similar to those in the general population and that reproductive history may be used to improve risk prediction in carriers.     

The effect of Sendai virus infection on bactericidal and transport mechanisms of the murine lung

Pulmonary virus infections predispose to bacterial infections in the lung. The mechanism of this effect was studied by quantitative comparison of the effects of airborne acute viral infection on pulmonary transport vs. in situ bactericidal mechanisms in mice. Animals infected by aerosol with 10(4) TCID(50) of Sendai virus developed pathologic pulmonary changes of interstitial pneumonitis, bronchial epithelial desquamation, and peribronchial mononuclear cell infiltration 7 days later. At that time, the mice were challenged with an aerosol of viable (32)P-labeled Staphylococcus aureus. Pulmonary bactericidal activity and physical transport by the lung were determined by the determination of viable staphylococcal and (32)P radiotracer counts respectively at 4, 24, 48, and 72 hr after bacterial challenge. Infected mice showed a significant decrease from normal in the rate of reduction of viable bacterial counts in the first 4 hr after challenge followed by a proliferation of the staphylococci. By contrast, radiotracer removal rates at 4 and 24 hr were similar in infected and noninfected mice. There was a small but significant retention of (32)P in the lungs of the infected animals at the later periods. These data demonstrate that bacterial multiplication associated with virus infection of lungs is related to defects in in situ bactericidal (phagocytic) mechanisms rather than transport mechanisms of the lung, despite histologic evidence of extensive destruction of bronchial-ciliated epithelium.     

Epidemiologic studies of coronary heart disease and stroke in Japanese men living in Japan, Hawaii and California: distribution of biochemical risk factors.

Distributions of serum cholesterol, glucose, uric acid and triglycerides are examined among Japanese men living in Japan, Hawaii and California. Laboratory methods are described in detail and efforts to assure comparability of these methods. In every age group studied, the mean, median and percentile for each of the biochemical variables are lower for men in Japan than in Hawaii and California.     

The feeding of diets containing up to 10% monosodium glutamate to beagle dogs for 2 years

Beagle dogs were fed diets containing either 5.13% w/w sodium proprionate or 2.5, 5.0 or 10.0% w/w monosodium glutamate (MSG) for 104 weeks. There were no adverse effects upon bodyweight gain, economy of food consumption, general behaviour, ECG, ophthalmological findings, haematology, blood chemistry, organ weights or mortality by comparison with control dogs receiving the basal diet. Urinary volume and sodium excretion were slightly raised in dogs receiving sodium propionate or MSG, but the ability to concentrate urine was unimpaired and there were no histological differences between treated and control animals.