The BRCA1 and BRCA2 gene mutations in women are associated with an increased risk of developing breast cancer, variously estimated at 50-80% lifetime risk, as well as an increased risk of ovarian cancer (and an increased risk of prostate cancer in men). In general, such estimates have been derived from statistical inferences, and not from actual large-scale observational studies. Based upon the latest data, fewer than 10% of all breast cancer patients harbor either of these gene mutations. Among the general population in the US, 0.2% of people are estimated to harbor one or both gene mutations. However, the incidence of these mutations in the Ashkenazi Jewish population is ten-fold greater than the general population, with approximately 2.65% of Ashkenazi Jews carrying one or both mutated genes. A new study in the journal Science studied a group of 1,008 Ashkenazi Jewish women who had all previously been identified as having either the BRCA1 or the BRCA2 gene mutation. Using sophisticated genetic testing of the women and their relatives, the study determined that the overall lifetime risk of developing breast cancer with either mutation was about 82%, which is at the high end of previous estimates.

Interestingly, the risk of breast cancer associated with these gene mutations appears to be increasing over time. Among the women with either mutation born before 1940, the risk of developing breast cancer by age 50 was 24%, while women with either mutation who were born after 1940 experienced a 67% risk of developing breast cancer by age 50. This is an important finding, as it suggests that, just as with so-called "sporadic" breast cancers (i.e., all cases of breast cancer not associated with either BRCA1 or BRCA2 gene mutations), there are other factors at work in the burgeoning incidence of breast cancer in the developed world.

These findings also point out an important principle operative in many diseases with a genetic basis: environmental and other non-genetic factors may enhance or diminish the risk of diseases associated with specific gene mutations. In the case of breast cancer, the progressively earlier onset of puberty in girls, hormone replacement therapy in postmenopausal women, the increasing levels of obesity in our society, and dietary or other environmental factors have all been proposed as potential causative factors behind the rising incidence of breast cancer in the US.

The study also found that, just as with "sporadic" breast cancer, women with either gene mutation who engaged in frequent physical exercise experienced a significant delay in the onset of breast cancer. This finding also was observed among women who avoided obesity, particularly during adolescence.

The lifetime risk of ovarian cancer was also studied in these women. For women carrying the BRCA1 gene mutation, there was a 54% lifetime risk of developing ovarian cancer, while women carrying the BRCA2 gene mutation experienced a 23% risk of ovarian cancer.

This study is an important contribution to our understanding of the two gene mutations currently associated with an increased breast cancer risk, as well as other non-genetic factors that might play a role in modulating the cancer-associated risks of these gene mutations.

POTENTIAL IMPACT OF MANDATORY CHILD-RESTRAINT SEATS ON COMMERCIAL AIRPLANES

The Federal Aviation Administration (FAA) has proposed that all children younger than 2 years of age be required to sit in separate child-restraint seats on all commercial airline flights, and that they no longer be permitted to ride in their parents' laps. Although the FAA has recommended that airline companies offer discounts for families traveling with such children, the airlines are under no obligation to do so, and in the current air travel economic environment, significant discounts for an extra airplane seat for Junior's car seat seem unlikely.

An interesting study in the current issue of the Archives of Pediatric & Adolescent Medicine looks at the potential public health impact of this proposed policy, and arrives at a worrisome conclusion. The authors evaluated the current risks of child death due to airline travel and automobile travel, and then estimated the potential risks of accidental death that might be associated with parents choosing to travel by automobile, instead of by plane, if the FAA policy is implemented.

Based upon the statistics and calculations used in this study, it was estimated that the mandatory use of child-restraint seats for all children under the age of 2 would result in the prevention of only 0.4 deaths per year due to commercial airplane accidents. This tiny number is based primarily upon the exceedingly low risk of death due to commercial airline accidents. After studying the current rates of accidental deaths for both automobile and commercial airplane passengers, the authors then calculated the point at which a switch from airplane travel to automobile travel would begin to adversely impact accidental death rates. As travel by automobile is, statistically, far riskier than travel by commercial airplane, any policy that shunts travelers from airplanes to automobiles will, at some point, begin to impact on the death rate due to accidents.

The study determined that if 5-10% of all families switched from air travel to automobile travel, a net increase in accidental deaths would result. The authors concluded that the cost of the FAA's proposed policy, in terms of lives lost and the economic costs of those deaths, would be prohibitive if it caused as few as 5% of families to choose travel by automobile instead of air travel.

MAGNETISM & DEPRESSION

Despite the revolution in drug therapy for depression, as many as half of all patients with serious depression will fail to respond favorably to these drugs. Many of these patients can still be helped with electroconvulsive therapy (ECT), also know as "electro-shock therapy." However, ECT can be associated with memory loss, which can be severe in a minority of patients. Moreover, the negative connotations associated with ECT after its inaccurate depiction in the movie "One Flew Over the Cuckoo's Nest" have also increased patient reluctance to undergo what can, in some patients, be a truly life-saving procedure.

There have been a few studies that have looked at the use of magnetic pulses, painlessly and non-invasively delivered to the brain through an intact skull, in patients with major depression that is refractory to antidepressant medications and psychotherapy. A new randomized double-blind study in the Archives of General Psychiatry applied both high-frequency and low-frequency transcranial magnetic stimulation to 60 patients with treatment-resistant depression.

The study found that both modalities of magnetic therapy, when applied intermittently for at least 4 weeks, significantly-and equally-ameliorated the symptoms of depression in patients who had failed to improve with multiple different antidepressant medications. Moreover, the treatment was painless, and was not observed to be associated with any apparent complications.

Dr. Robert A. Wascher