NYCRA NEWS- Genetic Predisposition (Vol. 1- Spring Issue 2024)
When a specific cancer type is prevalent in one side of the family, the cancer is recognized as a FAMILIAL cancer. Most of them are caused by genetic mutation in a gene related to cancer susceptibility. In addition, a term called "family cancer syndrome" (or "hereditary cancer syndrome") is a rare disorder in which family members have an above-average chance of developing a certain type or types of cancer. Family cancer syndromes are caused by inherited genetic variants in certain cancer-related genes. [1]
It is reported that up to 10% of all cancer cases may be caused by inherited genetic mutation or changes. These are called CANCER PREDISPOSITION genes. Individuals who carry a mutant allele of these genes have an increased susceptibility to cancer. It is now widely identified that an accumulation of genetic or epigenetic alterations affect the conversion of normal cells to cancer cells. [2]
GETETIC MUTATIONS
Oftentimes, researchers of hereditary cancers will reference breast cancer gene 1 (BRCA1) and breast cancer gene 2 (BRCA2). Specific alterations in these genes disable their function such that, inheriting such mutations may preclude you to contract breast (and other) cancers. Having a strong history of breast cancer may often be linked to acquiring a BRCA1 or BRCA2 mutation. Family members with BRCA1 or BRCA2 mutations often share the same mutation. [3]
Another predisposition scenario is Lynch syndrome; according to the CDC, carrying this condition holds a 1 in 2 (50%) heredity chance of your children also having Lynch syndrome. Genetic testing for Lynch syndrome can be considered once your children reach adulthood. Similarly, the most common are hereditary breast and ovarian cancer (HBOC) syndrome. Anyone with HBOC syndrome holds a higher risk for breast and ovarian as well as advanced and pancreatic cancers. [4]
Today's advancements in genetic tests can determine the possibility of an elevated risk of cancer. For those who come from a family with a history of breast and ovarian cancer make screening and treatment decisions. Not everyone needs to get genetic testing for cancer risk. Your doctor or health care provider can help you decide if you should get tested for genetic changes that increase cancer risk. They will likely ask if you have certain patterns in your personal or family medical history, such as cancer at an unusually young age or several relatives with the same kind of cancer.
Physicians may recommend genetic testing. It is advised to start with a genetic counselor who presents the potential risks, benefits, and drawbacks of genetic testing in your situation. Genetic counselors are also trained to review genetic test results with patients and/or their families and provide guidance in decision-making from those results. There are at-home genetic tests that one can order directly. Thanks to Dr. Google, there's more information on the types of consumer-accessible tests on the market- but these tests may have drawbacks or limitations when it comes to the prospect of genetic predisposition and genetic changes that increases cancer risk. Genetic counselors may be a helpful resource for identifying these test products as well.
For more information on what tests are available and who may want to consider them, visit the NIH/NCA Genetic Testing for Inherited Cancer Susceptibility Syndromes. https://www.cancer.gov/about-cancer/causes-prevention/genetics/genetic-testing-fact-sheet
REFERENCES
1) The Genetics of Cancer: NIH- https://www.cancer.gov/about-cancer/causes-prevention/genetics#:~:text=A%20family%20cancer%20syndrome%2C%20also,in%20certain%20cancer%2Drelated%20genes. The Genetics of Cancer | 2) Cancer predisposition genes: molecular mechanisms and clinical impact on personalized cancer care: examples of Lynch and HBOC syndromes - Published online 2015 Nov 30. doi: 10.1038/aps.2015.89 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4753377/#:~:text=Up%20to%2010%25%20of%20cancers,an%20increased%20susceptibility%20to%20cancer. | 3) Family Health History and the BRCA1 and BRCA2 genes/ CDC Centers for Disease Control and Prevention- https://www.cdc.gov/genomics/disease/breast_ovarian_cancer/fam_hist_genes.htm#:~:text=Normally%2C%20the%20BRCA1%20and%20BRCA2,%2C%20ovarian%2C%20and%20other%20cancers. | 4) Family Health History and Cancer: Which Hereditary Conditions Raise My Chances of Getting Cancer? / CDC Centers for Disease Control and Prevention- https://www.cdc.gov/cancer/family-health-history/index.htm#:~:text=Several%20hereditary%20conditions%20can%20raise,advanced%20prostate%2C%20and%20pancreatic%20cancers.
Part 2: CANCER PREDISPOSITION & THE ROLE OF GENETIC TESTING
By: Roberta Kline, MD
Especially with breast cancer, we know that 90% of the cases are not due to known inherited genetic mutations like BRCA1. The majority of them are due to very small changes in your DNA that interact with your environment over your lifetime that predispose you to developing breast cancer. But if you don't know that you have these predispositions, you can unknowingly be exacerbating the problem. If you've been tested and you know what your genes are doing, you can proactively create a plan to minimize your risk throughout your lifetime.
"INHERITING CANCER & GETTING THE RIGHT TEST"
We understand genetic mutations to cause severe diseases, predominantly causing certain types of cancers. But rather than living in fear of what you may or may not have inherited from your parents, and whether you may or may not develop the same diseases that they carried- get tested, so you won't find yourself guessing. Through gene testing protocols, you can precisely identify where you need to focus your resources, your attention- and when you can let go of that (unnecessary) fear.
Because genetic testing can be very specific, one of the biggest challenges for proactive people about their health is to know WHAT to test for. What test do you use? Is there a test that's better for you than others? These are important questions and the amount of information available (while great) can be quite overwhelming. The best suggestion is to speak to a trained medical professional or a genetic specialist who can help you navigate through the vast collection of available tests to find what is right for you. What you want is a test that has value. And in order to have value, it needs to answer your questions and provide you a roadmap for what you can do proactively for your health for the future.
So when you look at the issue of breast cancer in Long Island and how it is tied to these environmental toxins, what you're seeing is these environmental toxins can potentially, if it's a large enough dose, create mutations in somebody's DNA, but what is most likely happening (and this I do have to check on,) what is most likely happening is it's overwhelming the body's ability to process these toxins. When your body processes any kind of chemical, including these toxins, it produces oxidative stress. When you have too much oxidative stress for your body to handle, this has a tendency of creating DNA breaks. So it's not the toxin directly causing DNA breaks necessarily, it's that your body can't get rid of that toxin fast enough or efficiently enough. And so its own biological processes that are supposed to deal with this are the ones that actually cause the DNA breaks (mutation) and the changes in the DNA that increase the risk of breast cancer.
This is the second part of that pathway by which estrogen as well as other chemicals can cause breast cancer. Conventional medicine pays attention to the binding of estrogen to the estrogen receptor causing proliferation. Excessive proliferation can lead to a higher chance of DNA breaks. Every time that DNA replicates, (which is what happens when you create proliferation) when the cells grow, every time that DNA replicates, there's a chance that it will cause an error in that replication and leave a mutation in the DNA. Now, we have lots of processes that are built in to safeguard against that. We have DNA repair mechanisms, we have all sorts of machinery that is designed to catch breaks in the DNA before they get integrated into the person's biology. If you overwhelm that, those breaks stay.
To note, estrogen itself is a toxin, even though we produce it ourselves. Studying the other part of estrogen metabolism, which is the same process that happens with all of these toxins is that it goes through what we call DETOXIFICATION or BIOTRANSFORMATION. You're transforming something that's potentially toxic, ultimately into a molecule or a chemical that is non-toxic and gets eliminated from the body. Within that process, you are often creating even more toxic chemicals in the intermediary stages, and that's what requires a high level of antioxidant defense as well as other biological systems to keep those contained and keep them in check and funnel them quickly into the benign molecules out of the body. This is the second way that you can create DNA damage that you can create cancer because you are overwhelming the body's ability to neutralize those toxic compounds that your body is creating as a result of whatever it's taking in. This has to do with oxidative stress, which is linked to INFLAMMATION, which we know underlies almost every cancer process.
ABOUT THE AUTHOR
NON-INVASIVE IMAGING: REAL-TIME SCREENING OF DENSE BREAST TISSUE
(Special thanks to: Dr. Robert L. Bard, Cancer Imaging Specialist)
Between 2009 and 2019, 37 other states and D.C. passed legislation requiring notification of breast density, one of the last being my new home state of New Mexico. In 2019 a federal law was passed to require both clinician and patient reports contain plain language around the woman’s breast density, and to discuss with her provider. The FDA then created standard language that has now been implemented, requiring reporting on a woman’s individual breast density, and recommendation to discuss with her provider.
There is still much to be learned about what causes dense breasts and why women with dense breasts have an increased risk of breast cancer, and our ongoing study is one of many that are seeking to answer these questions at the molecular and genetic level. But the evidence that supplementing mammograms with other imaging modalities can increase the rate of early detection is substantial, and provides us with tools we can use right now to make a difference. [3,4] Despite this progress, there are still significant hurdles in changing the standard of care. A recent experience with my routine breast cancer screening highlighted the ongoing challenges. When I had asked to schedule an ultrasound with my screening mammogram, I was informed that it was not done this way – I could only get a mammogram. After my mammogram, I had to wait to receive my letter in the mail approximately one week later to be able to take any additional steps. The interpretation included a description of breast density and recommended to discuss any additional care with my physician.
Fortunately all was fine, but had I not been a physician that was fully aware of this issue, I would very likely have had only a mammogram and walked away with a dangerously false sense of security. This experience highlighted for me how much still needed to be done more than 20 years after my first experience. Legislation is only part of the solution. Clinician education and public awareness are the keys to changing how the intention behind these laws gets translated into actual change in health care. As I experienced, many clinicians are ill-informed about the nature of dense breasts, and options for adjunctive screening including ultrasound or MRI. This means that many of these reports end up being filed away with no further action being taken that could make a significant difference in early detection and saving lives.
Dense Breast Ultrasound Study
 |
| Molloy University Labs, NY. Dr. Noelle Cutter works with live breast cancer cells in dense breast tissue (Adenocarcinoma, breast, epithelial ER+ -estrogen receptor expressed). |
3/6-3/8/2024 – This observational study explores the functional phenotypic differences that make dense breast tissue. Because it is widely noted that women with dense breasts have a greater likelihood of developing cancer, understanding the pathways and changes in gene expression may offer the first avenue for the enzymes enrolled and drug targets for personalized medicine in pursuit of developing better treatment options.
Day 1: Dr. Cutter is establishing the effectiveness of the tissue culture methods, indicating the capability of growing the cells. Working with epithelial cells that are growing at the expected density rate, she is able to start extracting DNA, RNA and proteins. By running functional analysis, the study allows for the observation of cell reaction from oxidative stress in the cell line. Additional information gathered include apoptosis (to monitor the cellular death) vs. general growth rate to understand their growth properties.
Day 2: Part of the functional analysis include the induction of environmental stress to provoke oxidative stress response to record cell endurance within breast cancer cell lines. Over 36 trials showed response to oxidative stress which could mimic inflammatory response from environmental stresses. Reports indicate continued cellular survival and that “they're happy to keep growing… without any change in cellular deaths”. Activating oxidative stress included: physically adding stressors such as hydrogen peroxide, serum-starving and glucose-starving the cells- all presenting the same response.
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