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ESTABLISHING CAUSE and effect is one of the trickiest aspects of medicine. So-called ?causality? can be elusive, especially once you move beyond connect-the-dots type circumstances.
In Marin, we worry and wonder a lot about breast cancer. Why does a particular woman get breast cancer? How does another woman avoid it? These are difficult questions.
There are a litany of possible reasons why one might develop breast cancer. Even if we expand the question to what increases the risk of breast cancer across a broad population, satisfactory answers are slippery. It is with this in mind that we should view the recent evidence regarding breast cancer in Marin County.
It is well documented that Marin has historically had an abnormally high rate of new breast cancer cases. In particular, data from the late 1990s demonstrate breast cancer rates some 15 percent higher than those found across the rest of the state. Multiple culprits ? lifestyle, hormones, toxins and genetics ? have been proposed and studied.
A study recently published in the Journal of the American College of Surgeons has proposed yet another possible cause ? genetic differences in vitamin D receptors. The study, conducted by Dr. Kathie Dalessandri and colleagues, examined the DNA of 164 Caucasian women living in Marin and diagnosed with breast cancer between 1997 and 1999.
They compared their genetic profiles with
those of 174 breast-cancer-free matched controls and found that women who developed breast cancer were 1.9 times more likely to have a specific difference (called a variant) in the gene that dictates how the body utilizes vitamin D (the vitamin D receptor).
Vitamin D has received attention for its possible benefit in deterring certain types of cancers, and animal models have demonstrated that it has a beneficial effect on breast cancer tumor growth. So, differences in how vitamin D is processed by its receptors is a logical explanation for why certain women (in Marin and elsewhere) would be at higher risk for developing cancer.
But before you march out to determine your vitamin D receptor profile, let?s put these findings in prospective.
First, this was a small ?pilot? study and should be considered preliminary evidence. Medical practice and investigation is ripe with prominent associations that have not borne out in larger studies, such as oat bran and heart disease, and ? who can forget? ? vaccines and autism. In fact, there are more disproven associations in medicine than proven ones.
A much larger study of Marin Women (the ?Marin Women?s Study? www.marinwomensstudy.org) with 14,000 participants is ongoing, and analysis of their DNA samples (there are some 8,500 available) should provide more robust data on vitamin D receptor variants and genetic risk. Furthermore, the genetic data from Dalessandri?s study is from 15 years ago, during a time when breast cancer rates were peaking ? especially in Marin. While multifactorial, we know that this peak was, in part, because of combined postmenopausal hormone (estrogen and progesterone) therapy ? a known risk factor for developing breast cancer ? and a treatment more common then in Marin than elsewhere in California. So, we must be careful to extrapolate the findings regarding breast cancer risk from a prior generation to today?s milieu.
Finally, one must always be particularly fastidious when reviewing the results of studies that focus on a specific proprietary drug or test. While this study was funded by state, county and charitable sources, the results quite prominently affect the fortunes of genetic testing company InterGenetics Inc., which is marketing OncoVue, a ?genetic-based, breast cancer risk test.? So, while interactions between genes and the environment is certainly a promising field, the jury on vitamin D receptors and breast cancer is most definitely still out.
Where, then, does this leave us with breast cancer causality? There are some risk factors that we can confidently delineate. Some genetic risk is clearly proven ? and a family history of breast cancer is a known red flag. In terms of risky environmental exposures, an Institute of Medicine committee report released last year summarizes these nicely as ?hormone therapy that combines estrogen and progestin, exposure to ionizing radiation ? excess weight among post-menopausal women and alcohol consumption.?
Other environmental agents ? chemicals such as bisphenol A (BPA) ? have been implicated and are biologically plausible, but at this time they are unproven. Mary Mockus, a surgeon at Kaiser-Permanente San Rafael and a member of the collaborative Marin Women?s Study team, thinks the ?toxic soup? present in higher socioeconomic areas like Marin is likely to play some role in the higher breast cancer rates, but that we are unlikely to ever identify one clear-cut perpetrator. And, this then, fits quite well with what we know about causality in medicine.
So for Marin women, the best advice for preventing breast cancer is probably the best advice for preventing many diseases ? sleep well; get regular exercise; know your family?s medical history and discuss individualized screening plans with your doctor; don?t smoke; avoid excesses of alcohol, drugs and ionizing radiation; and eat plenty of green leafy vegetables. And a healthy vitamin D level ? ask your doctor ? won?t hurt either.
Dr. Dustin W. Ballard is an emergency physician at Kaiser Permanente San Rafael and the author of ?The Bullet?s Yaw: Reflections on Violence, Healing and an Unforgettable Stranger.? His Medically Clear column appears every third Monday; follow him on Twitter at http://twitter.com/dballard30.
Article source: http://www.marinij.com/marinnews/ci_21440076/dr-dustin-ballard-causes-breast-cancer-tricky-pinpoint
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