genetics


I thoroughly enjoyed the opportunity to talk to the breast cancer support group at the Jewish Family Services Center here in Dallas this week. This was my second visit with them and again I was impressed by the intelligence, passion and generosity of the women who are drawn to this program. This time I was introducing the idea of an integrated approach to anxiety and depression. According to the National Institute of Mental Health, the prevalence of depression in the general population in 2008 (the latest year for which statistics are available) is 6.7% of the adult population and the prevalence in women is 8.1%. Adding the diagnosis of breast cancer understandably bumps the prevalence slightly higher.

I reviewed the current pharmaceutical and nutraceutical approaches to depression and anxiety and also led the group through some paced breathing and the quick coherence technique of HeartMath. One woman announced that the breathing exercise made her feel calmer than she’d been all day!

During the discussion, one women raised the question about Tamoxifen and anti-depressants. Her oncologist told her that only a few anti-depressants could be prescribed to women on Tamoxifen. Since this is relatively new information, I’ve been researching the claim for the group and decided to post my findings here in the blog.

The concern stems from a study done in Ontario that was published in the British Medical Journal (Kelly CM et al. BMJ 2010 Feb 8:340). This reference is available on PubMed. The researchers looked at women over 66 who were on Tamoxifen and found that the mortality rate was higher in women on Paxil (paroxetine) versus some of the other antidepressants. The reason appears to be that Tamoxifen is broken down in our livers by an enzyme called cytochrome P450 2D6 (the name of this enzyme is often shortened to cyp2D6). Some medications including Paxil are also broken down by cyp2D6. If someone has a genetic variation such that this enzyme is not as efficient, they are often called poor metabolizers. This genetic variation is called a “snip” for the abbreviation single nucleotide polymorphism. If they are poor metabolizers, they will be unable to break down the Tamoxifen effectively and its benefit will be “blocked” by medications that use this pathway. (sort of like musical chairs and everyone is competing for the same seat) Paxil is metabolized by this pathway, so is Thorazine, Prozac, miconazole (a yeast medicine), and quinidine – to name just a few. If a medication has no inhibition or a weaker inhibition of cyp2D6, the Tamoxifen will be broken down more efficiently – for that reason the authors suggest Celebrex or Lexapro because they don’t compete as strongly for cyp2D6.

I read a review article by Kathleen Pritchard which was published in Breast Cancer Research Vol 12 Supp 4 (also on PubMed) and she notes that there are studies that refute the claim – one from Denmark, for example, and states that the final answer isn’t really known as far as SSRI’s and Tamoxifen. Some people are suggesting that we should test the urine for endoxifen (a break down product of Tamoxifen) and make sure that the drug is being effectively metabolized. This isn’t the standard of care as yet, nor is checking women to see if they have genetic SNP’s in their detox genes.

I’ve done the gene testing on people if they note a lot of side effects from a long list of medicines or if we’re suspicious of a problem. The testing is fairly expensive ($500 to $1000 depending on which genes we test) and is NOT covered by insurance. Another wrinkle in the discussion, whenever genetic screening comes up, is how likely is a SNP? We know from population studies of the SNP’s for cyp2D6 that about 6% of Caucasians are “poor metabolizers” of this gene. Other ethnic groups show poor metabolizer rates of 3.3% (Black North Americans), 8.4% (French), 7.7% (Southern Germans) and practically 0% in Korean and Chinese populations.

So, the take home message is Tamoxifen and anti-depressants can mix – but choosing a medicine that is less likely to interrupt the enzyme cyp2D6 is probably a good idea. Or better yet, learn coherence training and get regular acupuncture treatments!

Until next time, be well!

The LA Times article yesterday quoted an epidemiologist Rebecca Schmidt of the UC Davis MIND Institute saying that women who reported that they had not taken prenatal vitamins immediately before and during a pregnancy were twice as likely to have a child with autism. The researchers asked 700 women retrospectively if they were taking vitamins – a strategy that has been shown to be less than reliable. (Do YOU remember what you did six months or five years ago?) These women had children who were 2 to 5 years old and were diagnosed with autism. An interesting twist to the research was an attempt to stratify the women and screen them for two gene variants that are affected by taking supplemental folic acid and that have been linked to autism in prior research. The two gene variants were MTHFR and COMT. We’ve known that MTHFR (methylene tetrahydrofolate reductase) is a key enzyme in folic acid metabolism and that if a woman has a variant in this gene that she is at increased risk for giving birth to a child with neural tube defects. We also know that folic acid, vitamin B6 and vitamin B12 supplementation can “over ride” this gene uniqueness. COMT (catechol-o-methyl transferase) is a key enzyme involved in the metabolism of compounds such as catecholamines (epinephrine and norepinephrine), estrogens, and other pharmaceutical drugs and environmental toxins. B vitamins also may help negate the effect of this gene variant, but the situation is more complex than just adding vitamins.

So the LA Times article was helpful and reiterated what we’ve known for many years: prior to conception women (and probably also men) should supplement their diet with folic acid and other B vitamins. But claiming that autism rates were up to seven times higher in women with one of the gene variants was perhaps a little bit of a leap. (and attention-grabbing…because of course it got MY attention, right?!)

About the same time that the article was published I read an article in the Atlantic Monthly by David Freeman which chronicled the work of Dr. John Ioannidis. He is known for his mathematical models that show that most of today’s medical research is questionable. Quoting Freeman:

“In the paper, Ioannidis laid out a detailed mathematical proof that, assuming modest levels of researcher bias, typically imperfect research techniques, and the well-known tendency to focus on exciting rather than highly plausible theories, researchers will come up with wrong findings most of the time….His model predicted, in different fields of medical research, rates of wrongness roughly corresponding to the observed rates at which findings were later convincingly refuted: 80 percent of non-randomized studies (by far the most common type) turn out to be wrong, as do 25% of supposedly gold-standard randomized trials, and as much as 10% of large randomized trials. The article spelled out his belief that researchers were frequently manipulating data analyses, chasing career-advancing findings rather than good science, and even using th peer-review process to suppress opposing views.”

So, the upshot? I recommend prenatal vitamins prior to conception. I recommend a pre-conception visit to review health history, medications, supplements and screen a pap smear, a rubella titer and possibly genetic counseling depending on the prospective parents’ ages, ethnic backgrounds and family histories. A pre-conception visit is an excellent time to look at stress-management tools, work schedule adjustments, and possibly bring up parenting styles and beliefs for consideration. A thoughtful, planned pregnancy is ideal. Since upwards of two thirds of pregnancies are unplanned, however, I encourage daily vitamin use for all people who are sexually active.

Moments of sanity occasionally surface in news reports. I was pleased to see the recent “news of the week” in this week’s  Chemical and Engineering News (November 8, 2010), a weekly publication from the American Chemical Society. Federal attorneys reversed decades of government policy by claiming that genes – human and others – should not be eligible for patent protection because they are products of nature. Attorneys at the Department of Justice stated, “The U.S. has concluded that isolated but otherwise unaltered genomic DNA is not patent-eligible subject matter.”
Does that sound obvious? Did you realize that for the last two decades companies have been seeking and receiving patent protection for uncovering the gene “fingerprint” of specific genes? Technology has advanced to the point that the human genome has been completely mapped. The numbers are changing all the time, but we now know that there are roughly 30,000 genes in each of our cells. We have a vague idea of the function of about half of the genes. Company lawyers and DNA chemists have been racing to place their own rights on the genes as their intellectual property.
Can we find the balance between market pressures on companies to survive and our “rights” to our own DNA?

The psalmist said it in Psalm 139 verses 13 and 14 (NIV) For you created my inmost being; you knit me together in my mother’s womb. I praise you because I am fearfully and wonderfully made; your works are wonderful, I know that full well.

I guess that says it all for me….