Jewish World Review Oct. 27, 2003 / 1Mar-Cheshvan, 5763
By Robert A. Wascher, M.D., F.A.C.S.
http://www.NewsAndOpinion.com |
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
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
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.
JWR contributor Dr. Robert Wascher is an oncologic surgeon, professor of surgery, oncology research scientist, and author. He lives in Honolulu with his wife and two daughters.
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BRCA1/BRCA2: Breast & Ovarian Cancer Risks
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.
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.