Encouraging Genetic Testing For Longer Life ~ by Valerie Brown Cheers

Jolie decided to have her ovaries and fallopian tubes removed because of a BRCA1 gene mutation that puts her at increased risk for ovarian and breast cancers, she wrote in the New York Times on Tuesday.

Dr Diane Yamada, the University of Chicago’s chief of gynecologic oncology, said that while the effectiveness of the procedure is not 100%, it is “tremendous”.

Yamada was on the communications committee of the Society for Gynecologic Oncology in May 2013 when Jolie wrote about having a preventive double mastectomy because she carried the BRCA1 gene. “There was a huge spike in awareness after her original piece,” she said.

Researchers credited that piece for more than doubling the amount of genetic breast cancer tests in the UK, according to a study published in the journal Breast Cancer Research. Months after her editorial was published, referrals for that type of testing remained double the previous year’s figure.

Angelina Jolie

I am proud of Angelina Jolie for being so courageous in doing something which we as women really need to pay attention to also, and especially before having children.

Society has you thinking that DNA, genome, blood testing, etc is too expensive, but shouldn’t we as humans be paying more attention and perhaps having insurance which covers these types of testings which are so very important, even before making babies. The more we know the better we can improve our well-being!

I am not a scientist, nor may really know a whole lot about this DNA jargon, but I do and am very interested to find out why and how we can begin to end the DEGENERATIVE DISEASE being passed down to our children! Iwas born with it and have become very interested in and will keep on trying to help others prevent their babies being passed down deadly diseases which will only get worse, the older we get! We must begin to checking ourselves out, asking lots of questions, reading, researching and testing and using ourselves for studies instead of mice! We are no mice and we are human beings and have been using poor little mice for way too long and now it is time to test on humans, ourselves.

I have begun doing things with my own health, to see if my own health improves by doing my own holistic cures, i.e. meditation, music, water, etc. and sorry to say, don’t need any doctor telling me anything about my body, which we know about our very own bodies; and when they don’t see anything, like they did not see my mother’s progression of MS, I don’t believe in modern medicine, nor in a lot of doctors and not saying that doctors are bad, but just trust God over any man and He alerts me immediately when something is bad for me!

But I do know that God alerts us when something is abnormal and that goes for wrong foods, liquids, etc. anything which we put into our bodies and it is up to us to pay attention and react immediately! You feel the affect of it right away and this I truly know and if manmade medicines worked that way, people would only have to take one time and not 100’s of pills for a period of time!

I will never forget when I had a medicine reaction and it was Regulan! My face froze, I could hardly breath, but I told my nephew to call 911! My family made fun of me, but I actually looked like a maniquin because it froze my face immediately. When the ambulance got there, going to nursing school and knowing about reactions, I held onto the medicine and clinched it in my hands! I knew that when I got to the hospital they needed to know what I had taken which made me react! You could say, I saved my own life by holding onto that pill bottle tightly in my hands. But what was even better was how my nephew reacted so quickly which also saved my life. God is good!

A BRACA-1 – mutation associated DNA methylation signature in blood cells predicts sporadic breast cancer incidence and survival.

By Heather MacGibbon

A new Study published in the Journal of Clinical Oncology February, 2014 recommends removal of a patient’s ovaries by age 35 for women with the BRACA1 gene mutation.

According to this study, done internationally, waiting beyond this age increases risk of ovarian cancer before or at the time of preventative surgery and increases mortality rates. Women with the BRACA 2 mutation showed no increase past age 35 which suggest that they may delay preventative surgery longer.

“To me, waiting to have oophorectomy until after 35 is too much of a chance to take,” said Steven Narod, MD, professor of medicine at the University of Toronto in Canada and the study’s lead author. “These data are so striking that we believe prophylactic oophorectomy by age 35 should become a universal standard for women with BRCA1 mutations.”[1]

He added: “Women with BRCA2 mutations, on the other hand, can safely delay surgery until their 40s, since their ovarian cancer risk is not as strong.”[2]

The study showed that women with either mutation who had oophorectomy by age 35 experienced a 77% reduction in death from ovarian cancer before age 70.

Prior studies have shown that prophylactic oophorectomy reduces the risk of developing breast and ovarian cancers in women with BRCA1 or BRCA2 mutations. However, this is the first study to show an overall mortality reduction benefit. As many as 70 percent of women in the United States who learn they have BRCA mutations choose to have prophylactic oophorectomy. Many doctors recommend that such women undergo surgery by age 35 or when childbearing is complete. However, neither the optimum age for having this preventive surgery nor the effect of the surgery on the overall risk of death had been adequately studied.[3] In the Hereditary Ovarian Cancer Clinical Study, researchers from Canada, the United States, Poland, Norway, Austria, France, and Italy identified women with BRCA mutations from an international registry, 5,787 of whom completed questionnaires about their reproductive history, surgical history (including preventive oophorectomy and mastectomy), and hormone use. The study began in 1995, and the women were followed through 2011. Investigators examined the relationship between prophylactic oophorectomy and the rates of ovarian, fallopian tube, and primary peritoneal (abdominal) cancer, and the overall rate of death (total mortality) by age 70.[4]

Among the 5,787 women, 2,274 did not have oophorectomy, 2,123 had already had the surgery when they began the study, and 1,390 underwent oophorectomy during the study follow-up period. After an average follow-up period of 5.6 years (with some women followed as long as 16 years), 186 women developed either ovarian, fallopian tube, or peritoneal cancer.[5]

Overall, the investigators found that oophorectomy reduced the risk of ovarian cancer by 80 percent. For women who carry a BRCA1 mutation, the authors estimate that delaying the surgery until age 40 raised the risk of ovarian cancer to 4 percent; ovarian cancer risk increased to 14.2 percent if a woman waited until age 50 to have the surgery. In contrast, only one case of ovarian cancer was diagnosed before age 50 among BRCA2 mutation carriers in this study. By comparison, the lifetime risk of ovarian cancer in all women (including those without BRCA mutations) is only 1.4 percent.[6]

Of the 511 women who died during this study, 333 died of breast cancer, 68 from ovarian, fallopian tube, or peritoneal cancers, and the remainder from other causes. Prophylactic oophorectomy reduced the risk of death by any cause by 77 percent (largely by lowering the risks of ovarian, fallopian tube, peritoneal, and breast cancers). Dr. Narod noted that the 77-percent risk decrease is even greater than the benefit of chemotherapy, and was equally strong for both BRCA1 and BRCA2 mutation carriers.[7]

In a prior study by this group, oophorectomy was also shown to reduce the risk of breast cancer by 48 percent in women with a BRCA1 mutation, and once diagnosed, lowered the risk of breast cancer death by 70 percent.[8]

[1] American Society of Clinical Oncology (ASCO). “Preventive ovarian surgery should be performed early for greatest benefit; substantial mortality risk reduction found.”

 What is the epigenome?

A genome is the complete set of deoxyribonucleic acid, or DNA, in a cell. DNA carries the instructions for building all of the proteins that make each living creature unique.

Derived from the Greek, epigenome means “above” the genome. The epigenome consists of chemical compounds that modify, or mark, the genome in a way that tells it what to do, where to do it and when to do it. The marks, which are not part of the DNA itself, can be passed on from cell to cell as cells divide, and from one generation to the next.

What does the epigenome do?

Each person’s body contains trillions of cells, all of which have essentially the same genome. Yet some cells are optimized for use in muscles, others for bones, the brain, the stomach and the rest of your body. What makes these cells different?

The protein-coding parts of your genome, called genes, do not make proteins all of the time in all of your cells. Instead, different sets of genes are turned on or off in various kinds of cells at different points in time. Differences in the types and amounts of proteins produced determine how cells look, grow and act. The epigenome influences which genes are active – and which proteins are produced – in a particular cell.

So, the epigenome is what tells your skin cells to behave like skin cells, heart cells like heart cells and so on.

 Is the epigenome inherited?

Just as the genome is passed along from parents to their offspring, the epigenome can also be inherited. The chemical tags found on the DNA and histones of eggs and sperm can be conveyed to the next generation.

What is imprinting?

Your genome contains two copies of every gene – one inherited from your mother and one from your father. For some genes, only the copy from the mother ever gets switched on, and for others, only the copy from the father. This pattern is called imprinting.

The epigenome serves to distinguish between the two copies of an imprinted gene. For example, only the father’s copy of a gene called IGF2 is able to make its protein. That is because marks in the epigenome keep the mother’s IGF2 copy switched off in every cell of the body.

Some diseases are caused by abnormal imprinting. They include Beckwith-Wiedmann syndrome, a disorder associated with body overgrowth and increased risk of cancer; and Prader-Willi and Angelman syndromes, which are disorders associated with obesity and MENTAL RETARDATION.

How do changes in the epigenome contribute to cancer?

Cancers are caused by a combination of changes to the genome and the epigenome.

Adding or removing methyl groups can switch genes involved in cell growth off or on. If such changes occur at the wrong time or in the wrong cell, they can wreak havoc, converting normal cells into cancer cells that grow wildly out of control.

For example, in a type of brain tumor called glioblastoma, doctors have had some success in treating patients with a drug, called temozolomide, that kills cancer cells by adding methyl groups to DNA. But that’s only part of a very complex picture. Cells also contain a gene, called MGMT, that produces a protein that subtracts methyl groups – an action that counteracts the effects of temozolomide. In some glioblastomas, however, the switch for the MGMT gene has itself been turned off by methylation, which blocks production of the protein that counteracts temozolomide. Consequently, glioblastoma patients whose tumors have methylated MGMT genes are far more likely to respond to temozolomide than those with unmethylated MGMT genes.

Changes in the epigenome also activate growth-promoting genes in stomach cancer, colon cancer and the most common type of kidney cancer. In other cancers, changes in the epigenome silence genes that normally serve to keep cell growth in check.

To come up with a complete list of all the possible changes that can lead to cancer, the National Institutes of Health (NIH) has started a project called The Cancer Genome Atlas. Beginning with glioblastoma, these researchers are comparing the genomes and epigenomes of normal cells to those of cancer cells. They are looking for any changes in the DNA sequence, called mutations; changes in the number and structure of chromosomes; changes in the amounts of proteins produced by genes; and changes in the number of methyl groups on the DNA.

Understanding all the changes that turn a normal cell into a cancer cell will speed efforts to develop new and better ways of diagnosing, treating and preventing cancer. To learn more about this effort, go to http://cancergenome.nih.gov.

How are researchers exploring the epigenome?

Researchers are exploring the epigenome through a field called epigenomics, which is the study of all the chemical tags on the genome that control the activities of genes. This is different from genomics, which is the study of all the changes that occur in the order, or sequence, of the DNA building blocks that make up the genome.

Experts once thought that diseases were caused mainly by changes, or mutations, in DNA sequence – changes that either disrupt protein production or lead to abnormal proteins. Recently, researchers have learned that changes in the epigenome may cause or contribute to many diseases, making epigenomics a vital part of efforts to better understand the human body and improve human health.

As part of its Roadmap for Medical Research, the NIH plans to develop a map of the epigenomic marks that occur on the human genome. The effort will require the development of better technologies to quickly and efficiently detect epigenomic marks, as well as improved understanding of the factors that drive these changes. To learn more about this effort, go to http://commonfund.nih.gov/epigenomics.

Human Epigenome Pilot Project

The Human Epigenome Consortium is a public/private collaboration that aims to identify and catalogue Methylation Variable Positions (MVPs) in the human genome. As a prelude to the full-scale Human Epigenome Project (HEP), we have recently completed a pilot study of the methylation patterns within the Major Histocompatibility Complex (MHC) – a region of chromosome 6 that is associated with more diseases than any other region in the human genome.

We have identified MVPs in the vicinity of the promoter and other relevant regions of approximately 150 loci within the MHC in tissues from a range of individuals. This will provide an unprecedented insight into the complex relationship between genetics and epigenetics that underlies both normal cellular homeostasis and disease states, in particular autoimmune diseases.

For the pilot project, we developed an integrated genomics-based technology platform. The pipeline involves the automated bisulphite treatment of DNA from minute tissue biopsies, gene-specific bisulphite PCR and large-scale sequencing of PCR amplicons. Analysis and quantification of methylation patterns is achieved by mass spectrometric and microarray assays.  http://www.epigenome.org/index.php?page=pilotproject

Human Epigenome Consortium

Updated February 19, 2015: 23andMe provides ancestry-related genetic reports and uninterpreted raw genetic data only. We intend to add some health-related genetic reports in the future once we have a comprehensive product offering. At this time, we do not know which health reports might be available or when they might be available. For more information, please go to the health page. https://www.23andme.com/

ScienceDaily. ScienceDaily, 24 February 2014. <www.sciencedaily.com/releases/2014/02/140224171145.htm>.

[2] IBID

[3] IBID

[4] IBIDA. P. M. Finch, J. Lubinski, P. Moller, C. F. Singer, B. Karlan, L. Senter, B. Rosen, L. Maehle, P. Ghadirian, C. Cybulski, T. Huzarski, A. Eisen, W. D. Foulkes, C. Kim-Sing, P. Ainsworth, N. Tung, H. T. Lynch, S. Neuhausen, K. A. Metcalfe, I. Thompson, J. Murphy, P. Sun, S. A. Narod. Impact of Oophorectomy on Cancer Incidence and Mortality in Women With a BRCA1 or BRCA2 Mutation. Journal of Clinical Oncology, 2014; DOI: 10.1200/JCO.2013.53.2820

[5] IBID

[6] IBID

[7] IBID

[8] IBID






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