Monday, December 29, 2008

Breast Cancer Symposium

Mayo study further confirms the importance of CYP2D6 for tamoxifen effectiveness building the case for genotyping and medication management

Mayo gave a presentation on December 11th at the 31st annual San Antonio Breast Cancer Symposium that further confirms the importance of the liver enzyme CYP2D6 in tamoxifen effectiveness. Tamoxifen is often prescribed to block the effects of estrogen in breast tissue to prevent breast cancer recurrence in ER+ (estrogen receptor positive) cancers which require estrogen to grow and spread. Previous studies have already revealed that tamoxifen is less effective in women with reduced CYP2D6 activity caused by genetic variations or co-administration with medications that inhibit CYP2D6, but the mechanism of action for tamoxifen was not well understood.

Tamoxifen is a pro-drug that is metabolized and converted into the metabolites endoxifen and 4HT; both previously believed to play a key role in suppressing estrogen. However, Mayo’s study shows that endoxifen degrades estrogen receptors in breast cancer cells and is the key metabolite involved in the effectiveness of tamoxifen. Since CYP2D6 is the enzyme that converts tamoxifen to endoxifen; this study further indicates that widespread genotyping and medication management can improve outcomes for many of the 35% of ER positive breast cancer patients who currently fail tamoxifen treatment.

On October 18, 2006, an FDA Advisory Subcommittee was convened to review the tamoxifen research findings to date and to make a recommendation regarding a label change. The consensus of the Subcommittee was that the label should be updated to reflect the fact that postmenopausal women with ER-positive breast cancer who are CYP2D6 poor metabolizers treated with tamoxifen (by genotype or drug interaction) are at increased risk for breast cancer recurrence. This label change has still not been made, and now the case is even stronger.
So, what can be done with this information to reduce the risk of breast cancer recurrence?
First, genotyping should be considered for every ER-positive breast cancer patient taking tamoxifen. Insurance typically covers testing, and alternative therapies exist for treatment for the 10% of patients who are CYP2D6 poor metabolizers.

Second, medication management involving the careful monitoring of tamoxifen co-administration with other medications, herbals, and over-the-counters needs to happen. For example, “hot flashes,” a common side effect of tamoxifen, are typically treated with selective serotonin reuptake inhibitors, and fluoxetine, paroxetine and high doses of sertraline are notoriously potent CYP2D6 inhibitors. Additionally, 35% of patients are CYP2D6 intermediate metabolizers and are at risk with less potent inhibitors of CYP2D6 such as the commonly used herbal goldenseal as shown in the interaction report below.

Genelex includes access to GeneMedRx drug and gene interaction software with each tamoxifen CYP2D6 test so healthcare providers and patients can quickly see if co-administration is going to reduce CYP2D6 activity.

Mayo’s study has confirmed the critical role of CYP2D6 in tamoxifen treatment. It is time to start putting this research to use in the clinic.

Wednesday, December 17, 2008


The genetic code in your DNA breaks down into just four basic building blocks or nucleotides represented by letters: A/adenine, T/thymine, G/guanine, C/cytosine

More than 99% of human DNA sequences are the same across human populations. The main differences occur when a single nucleotide (A,T,C,or G) in the genome sequence is altered.
These single letter changes are called single nucleotide polymorphisms or SNPs (pronounced "snips"). For example a SNP might change the DNA sequence from AAGGCTAA to ATGGCTAA.
SNP’s represent about 90% of human genetic.

Tuesday, December 16, 2008

Only DNA Testing Can Tell. Twins- Identical? Fraternal?

Approximately one in every eighty births results in the delivery of twins. Although the misconception persists, the number of placentas cannot determine if same-sex twins are fraternal or identical - only DNA testing can. One third of identical twins have two placentas and more than 40% of fraternal twins have a single, fused placenta.

DNA testing to determine if twins are identical or fraternal is called twin zygosity testing. Twins that are dizygotic or fraternal are the result of two different sperm fertilizing two different eggs and share only the same amount of DNA as full siblings born at different times.

Monozygotic or identical twins are the result of one egg fertilized by a single sperm that splits in two and have identical DNA. Most twins have zygosity testing performed simply to satisfycuriosity. However, knowing if twins are identical or fraternal can be a safeguard for possible future medical emergencies—identical twins are perfect organ and tissue donors for one another.

Although identical twins often look so much alike that we have difficulty recognizing one from the other, many do notbecause their genes express themselves in different ways. Alternatively, fraternal twins can appear to be identical when they are not, like the famous Olsen twins. If you are a twin or know a twin that has ever wondered, DNA testing is the only way to answer the question with certainty.

Friday, November 14, 2008

Warfarin DNA Testing Predicted to Save Over One Billion Dollars and Improve Patient Safety

The AEI-Brookings Joint Center for Regulatory Studies released a study in November, Health Care Savings from Personalizing Medicine Using Genetic Testing: The Case of Warfarin that confirms that DNA testing will dramatically improve the safety and effectiveness of Coumadin (warfarin).

Warfarin, brand name Coumadin, is a powerful medicine that saves hundreds of thousands of lives every year. It works by “thinning” the blood and preventing clots that would otherwise cause strokes, heart attacks, or other blood clotting disease. Every year as many as two million Americans start taking warfarin and at any given time there are four or five million on the medicine.

The amount of warfarin required for someone to reach their target INR, the measure of the effectiveness of warfarin, varies as much as forty-fold from person to person. This interpersonal variation in warfarin dose requirement makes it time consuming and dangerous to identify the optimal dose for patients. Dangerous because the therapeutic window, the difference between the effective dose and the toxic dose of warfarin, is exceedingly small. The consequences of warfarin over-dosing are also severe — resulting bruising and bleeding are the second most prevalent cause of emergency room visits and are responsible for thousands of deaths every year. There are some safer, replacement drugs in development, but they are still at least three or four years away from being ready for market.

During the last decade scientists have discovered that most of the individual variation in warfarin dose requirement is due to genetics or variation in the DNA of individual patients. This variation, for which genetic tests are now available at the initiation of warfarin therapy, occurs at two sites on the DNA. The most important, known as CYP2C9, controls the levels of the enzyme that’s responsible for the breakdown and elimination of warfarin. Approximately 35% of the population have variant forms of this enzyme that slow down the elimination of warfarin from the system. Instead of a person reaching their warfarin and INR steady state in four or five days, it can take two weeks or more. Genetic testing is the only reliable way to determine when steady state is reached.

The second most important site of genetic variation affecting warfarin maintenance dose is the vitamin K receptor (VKORC1), the site of action of warfarin. This makes sense as it is well known that vitamin K intake affects the action of warfarin. Genetic variation is common at this site. Ninety percent of Asian-Americans have the "low-dose" variation: meaning they required a lower dose of warfarin, while most African-Americans have the "high-dose" variation requiring more drug to get adequately anticoagulated. Patients of European descent fall somewhere in the middle.

When people have DNA testing there are now computer programs that take into account their genetics, age, sex, weight and other factors, such as amiodarone or other medicines they may be taking to calculate their warfarin dose. This calculated dose is many times more accurate than the dose determined without the DNA testing.

Patients need to be proactive in obtaining this testing. Adoption of the testing by doctors and anticoagulation clinics is slow, despite endorsement by leading scientists, the FDA, and patients who have had the testing and credit it with saving them from the dire consequences of a warfarin overdose. Additionally, uptake has been slow because of the inherent conservatism of the medical establishment and lack-luster interest from pharmaceutical manufacturers.

Widespread adoption of DNA testing to predict warfarin dose will cut down on doctor and emergency room visits and save thousands of lives. A recent Brookings/American Enterprise Institute study estimates that routine use of DNA testing would save the healthcare system as much as $2 Billion per year. It will also help make warfarin therapy more accessible to the millions of people who are not now taking warfarin but who would benefit from it.

Monday, November 10, 2008

DNA & Godfather of Soul

The Godfather of Soul is also a father many times over. In addition to six children of record, three additional children have now been proven to have been fathered by the late soul singer, James Brown. About a dozen DNA tests have been performed since he died in December 2006 of heart failure at the age of 73. Some people have been ruled out as Brown's children, while other tests are still pending.

The emerging offspring are adding even more twists to the legal squabbling that emerged after the Sex Machine's death. The estate disputes between the singer's children already involves as many as two dozen lawyers.

Friday, November 7, 2008


It takes about eight hours for one of your cells to completely copy its DNA.

You could fit one million threads of DNA across the period at the end of this sentence.

If you were to start reciting the order of the ATCGs in your DNA tomorrow morning, at a rate of 100 each minute, 57 years would pass before you reached the end (provided that you did not stop to eat, drink, sleep, use the bathroom etc.)

Our genes are remarkably similar to those of other life forms. For example, we share 98% of our genes with chimpanzees, 90% with mice, 85% with zebra fish, 21% with worms, and 7% with a simple bacterium such as E. coli.

Friday, October 31, 2008

Mitochondrial DNA Tests—What Else Can They Reveal?

Mitochondrial DNA (mtDNA) testing is now commonly being used to trace female ancestry. MtDNA is passed only from a mother to her children so it gives us the unique ability to glance back in time at our female lineage; some people even use this test to confirm a suspected common female ancestor such as a great-great grandmother.

When genetic scientists examine mtDNA; they compare two portions called hypervariable region I and II to an agreed upon reference set called the Cambridge Reference Sequence. Everyone's DNA is almost identical in this portion; however, the differences are used to place you in one of 33 major “haplogroups” popularly called "clans." If you are in the same clan, you share a common female ancestor. There have been different maternal lines in existence in human
lines in existence in human history, history, but these are the only lines that can be found in existence today.

Typically a genetic testing lab will send you a report that shows how your DNA varies from the Cambridge Reference Sequence, your haplogroup designation, information about where and when your haplogroup originated, and where it exists today. Genelex offers the most in-depth haplogroup report available, but there is more information you can find if you are willing to dig a little deeper. For instance, if you happen to be in one of the haplogroups of Eurasion origins, you can read The Seven Daughters of Eve by Bryan Sykes who tells a story of what life was probably like for the original women who started the Eurasian lines.

Interested in finding your genetic cousins? If you go to; you can enter in your mtDNA results to find genetic matches; people with an identical mtDNA signature are related to you in the more recent past. If you are interested in finding people in the same haplogroup, you can do a halpogroup search to find other members of your “clan.” Keep in mind that for haplogroup matches, your common ancestor may have walked the earth over 10,000 years ago or more.

To find out more about Ancestry DNA Testing visit:

Wednesday, October 29, 2008


Nearly one third of breast cancer patients prescribed tamoxifen currently fail treatment. According to the National Foundation for Cancer Research (NFCR), this failure rate can be reduced to less than ten percent, saving 20,000 lives each year, by having patients take a simple DNA test and properly managing their medications.

Recent research shows that tamoxifen has to be activated into endoxifen by the liver enzyme CYP2D6. Endoxifen is the medicine that prevents the recurrence of estrogen receptive positive cancers.

About ten percent of breast cancer patients prescribed tamoxifen are missing CYP2D6 because of their DNA, and will fail tamoxifen treatment. “Patients want to know that tamoxifen will definitely benefit them, before committing to take it for five years. DNA testing offers them the reassurance that their tamoxifen is effective," stated Dr. Michael Benjamin, oncologist and editor of the medical news website,

Breast cancer patients can also fail tamoxifen treatment by unknowingly taking other prescription drugs, herbals preparations, or over-the-counter medicines that interfere with CYP2D6 activity. Many classes of drugs, including anti-depressants, prevent CYP2D6 from converting tamoxifen into endoxifen. That’s why Genelex includes password-protected access to their GeneMedRx software program with each test. Patients enter all of the drugs they take and produce a report to learn if any of the drugs they take might be defeating their endoxifen treatment.

“Patients and physicians need to be aware that DNA testing for tamoxifen effectiveness is available now. There is typically a 10-year gap between research and application in the clinical setting. We need to shorten that time when people’s lives are at stake- as they are with tamoxifen,” stated Genelex founder and CEO Howard Coleman.

For more information about the CYP2D6 DNA test, visit Genelex at Genelex donates a portion of all tests purchased to the National Foundation for Cancer Research.

Monday, October 27, 2008

DNA Testing Advances Aid In Depression Treatment

Almost one third of Americans currently take antidepressant medications and many have had problems finding the right drug and dose. This is not surprising to people that study genetics - research shows that of all the clinical factors such as age, sex, weight, general health and liver function that alter a patient's response to drugs, genetic factors are the most important.

Psychological disorders are complex and the number of treatments available in the United States continues to grow, but virtually all medications used to treat depression are metabolized by two enzymes in the liver: CYP2D6 and CYP2C19. Your genes are the main factor determining the level of these enzymes- if you have too much of the enzyme, you process the medication too quickly, too little of the enzyme and the medication builds up in your bloodstream potentially causing adverse reactions or side effects. Without knowing your genetics, your physician may need to go through months of trial-and-error prescribing to find the right drug and dose for you.
Testing of CYP2D6 and CYP2C19 has been available for several years to help your healthcare provider optimize your response to antidepressants, but Genelex has just recently made another test available that can help maximize treatment success. The new test helps determine a person’s response to serotonin-selective reuptake inhibitors (SSRIs) which are among the most commonly prescribed antidepressants. This class of medications includes citalopram, fluoxetine, paroxetine and sertraline among others, and often is prescribed for depression or anxiety. As a class of medications, the SSRIs have shown successful responses for many people—but not in everyone.
There are a number of reasons why some people may respond better than others to this class of drugs. Each person’s unique genetic make-up affects how their body absorbs, modifies and ultimately excretes any medication taken, but genetics also play a role in how a drug will exert its effect within the body. Researchers have found that mutations in some genes specifically change how effectively SSRIs may act.
SSRIs are known to exert their effect, in part, by blocking the serotonin transporter. This transporter is found in regions of the brain where antidepressants are active. The transporter causes less efficient signaling in the brain by reducing the amount of active serotonin—an important chemical associated with mood response. When SSRIs block the transporter, more serotonin is available for signaling which can improve mood.
Researchers are studying the serotonin transporter (5HTT) gene to further understand its role in SSRI efficacy. In a DNA region (known as the ‘promoter’), very near the 5HTT gene, a mutation has been found that affects how well persons respond to SSRIs. This mutation results in a shortened form (allele) of the transporter gene.
The short allele is associated with less response to SSRIs. Patients who have the short allele are less likely to respond to SSRIs or may take longer to respond. This effect is often found in those who carry two copies of the short allele, but can also occur in those who have one short and one normal (long) allele. About 40% of the North American population carries the short allele.
Genelex Chief Scientific Officer Dr. Teresa Aulinskas stated, "I am excited to give medical providers another tool that will help them better target therapy in the treatment of depression when finding the right drug and dose as early as possible is so critical." Many people with depression get better with standard treatments — medications and psychotherapy — and return to enjoying a happy, fulfilling life. However, for a significant percentage of people, depression treatment just doesn't work, and they continue to feel sad and hopeless, disinterested in activities, and perhaps even suicidal. DNA testing may offer the key to avoiding this in many cases.
To help healthcare providers utilize DNA Drug Safety testing to cater dosage and drug selection to a patient’s individual needs, Genelex includes a free 90-day subscription to our personalized medication management software, GeneMedRx, with each DNA Drug Safety test order. This online tool helps healthcare providers predict drug-drug and drug-gene interactions so medication regimens can personalized.

To learn more about the use of DNA Testing in the treatment of depression, visit

Friday, October 24, 2008

DNA Testing Helps Unwed Military Parents Get Benefits

Genelex has been assisting military personnel since our inception in 1987. We offer a 10% military discount on all of our DNA testing services to any person with a current military i.d. Although this discount is typically used for paternity testing, it also applies to our DNA Drug Safety, ancestry, nutritional genetic, and predictive genetic testing.

If the child of a military father is born when the parents are not married, DNA testing is a conclusive way to prove paternity so the child can get military benefits. In addition, establishing paternity provides children with equal rights and access to the benefits of Social Security, health insurance, survivor benefits, and inheritance rights.
Genelex DNA Testing Consultants are experts in handling all of the steps in the testing process; even in complex situations in which one or both parents are stationed overseas or one of the parents is no longer living. With over 20 years of experience meeting the unique DNA testing needs of military families, Genelex is the trusted lab for people in all branches of military service.