Have you heard about ‘Lynch Syndrome’?
Thank you for reading another issue of myStrand, your digest of the world of genetics and cancer. This month we are turning our focus towards a lesser known type of hereditary cancer, one of hereditary breast and ovarian cancer’s country cousins if you like, when it comes to the public spotlight and general awareness: Colorectal Cancer. Just like many other cancers, colorectal cancer comes in many disguises and does not discriminate by age or gender. Women and men of all ages are diagnosed, often much too late because symptoms are written off as digestive problems and ill-effects of a stressful lifestyle. However, late diagnosis means fewer treatment options, so being aware of the symptoms and knowing if your genes put you at a higher risk of getting colorectal cancer are essential. Read on to hear a patient’s story that spans the realms of colorectal and gynecological cancers as well as sarcoma, finally diagnosed as ‘Lynch Syndrome’ and to learn more about hereditary colorectal cancer and what to look out for to prevent it.
Please write to us with any questions about genetic testing or counselling as well as suggestions for topics that you would like to see covered in myStrand. You can reach us at email@example.com or through any of the communication channels of our #StayAheadOfCancer campaign.
The myStrand team!
When ‘Lynch Syndrome’ calls
This is a story about a large Indian family whose tragic tryst with cancer remained unexplained over several decades: brothers, sisters, parents, daughters, cousins, and nieces all afflicted with colon, breast, or ovarian cancers, some diagnosed as young as 32 years of age. Unfortunately, nobody joined the dots until 65-year-old Saraswathi started noticing a change in her bowel movements. She had to go more frequently and also started feeling pain in the lower abdomen occasionally. Keenly aware of the symptoms from her own daughter’s diagnosis of colon cancer several years earlier, she sought a consultation with a specialist.
Asking the right questions
A series of medical investigations later, Saraswathi (not her real name) was diagnosed with Stage 2 colon cancer. As part of the consultations, Saraswathi’s doctor also asked about any other instances of colon cancer, or any other cancers in her family. Surprised by the question at first, Saraswathi started to investigate her family’s unfortunate tryst with cancer a little more closely and unearthed several instances of cancer: In addition to her daughter’s colon cancer diagnosis at 32 years of age, her brother had suffered and died from sarcoma (a cancer in connective tissue or bones) in his early 40s, his now 48-year-old daughter (Saraswathi’s niece) had recently been diagnosed with a gynecological cancer; Saraswathi’s sister had been diagnosed with a gynecological cancer at the age of 48 years and unfortunately succumbed to the disease within a year; two of Saraswathi’s younger brothers were diagnosed with colon cancer at 42 years (he sadly passed away within a year) and 38 years (he still fights the disease), respectively, and Saraswathi’s father had died of colon cancer at the age of 50.
Acknowledging this extensive history of several cancers in Saraswathi’s family, the doctor recommended a genetic test to determine whether an inherited gene mutation might be to blame. Saraswathi was referred to the Strand Center for Genomics and Personalized Medicine for a genetic test that looks for inherited mutations in 19 genes known to increase hereditary cancer risk. The test identified a ‘pathogenic’ mutation (this means a mutation that is known to cause a disease) in a gene called MLH1. This gene is part of a group of genes responsible for repairing mistakes in our DNA that happened when our cells divide. When MLH1 is mutated it can no longer perform this repair function and random mistakes start accumulating in tissues where MLH1 would normally be most active. Hence, mutations in this gene increase the lifetime risk of getting several types of cancer, including colorectal (52-82%), endometrial (25-60%), gastric (6-13%), and ovarian (4-12%) cancers, compared to the average population risk of just around 1-5% for most cancers.
Having a mutation in the MLH1 gene, or in medical jargon ‘being a carrier of a MLH1 mutation’, means Saraswathi was diagnosed with ‘Lynch Syndrome’ (also known as hereditary nonpolyposis colorectal cancer or HNPCC). Lynch Syndrome is diagnosed when someone carries a mutation in at least one of several genes, including MLH1, MSH2, MSH6, and EPCAM. However, the key take away message from this diagnosis is, that considering Saraswathi’s family history, ‘Lynch Syndrome’ could potentially have been diagnosed much earlier and family members could have been warned about their higher cancer risk and advised genetic testing to confirm the presence of the same mutation. Especially, her daughter’s diagnosis of colon cancer at just 32 years of age should have been a red flag and prompted an investigation into any hereditary aspects to her cancer.
As always, the question in such cases is: Would knowing the hereditary status of her daughter’s or any of her other relatives’ cancer have made a difference? Is there anything Saraswathi could have done to avoid cancer altogether had she known of her higher risk status? The answer to both questions is a resounding ‘YES!’. Just like there are many preventive and screening options for hereditary breast and ovarian cancer, there are specific cancer screening and preventive options for Lynch Syndrome, too. Doctors and pathologists have clearly mapped out the journey that colon cells make from being benign growths (medical jargon for being harmless, like polyps for example) to becoming cancerous. Enter ‘The Adventure Colon’ – a tunnel you can walk through to discover what your colon looks like on the inside when it is healthy and observe the changes when its cells slowly become cancerous https://www.youtube.com/watch?v=vWaY-3O7ahk).
The light at the end of the tunnel
So does it make sense for everyone to get tested to assess his or her risk? Not really! Even in situations where more than one member of a family develops cancer, the culprit is most often exposure to a common toxin, such as cigarette smoke. Inherited forms of cancer are suspected under rarer circumstances, such as when cancers occur at a young age in a family – as in the case of Ashok, or when a person has more than one type of cancer, or if unusual forms of cancer are seen, such as breast cancer in men. The right person to help you decide whether the test is appropriate for you is a genetic counselor, who will recommend the test based on your medical and family history. Genetic counselors can also help you with understanding the test results and formulating the next steps. If you are a person with a high-risk for developing hereditary cancer, vigilance is essential to catch the disease early with regular check-ups and screens. The greatest success in cancer treatment arises when the disease is caught and treated early.
Saraswathi’s story is just one of many hereditary cancer cases that have come to light thanks to Strand’s genetic tests. Like Saraswathi, many have chosen to share their stories in the hope that another family might benefit, too. You can read their stories on our website.
Disclaimer: The information provided in this article is in no way intended to replace expert medical advice. Always discuss the best possible course of action for your situation with your doctor.
Impacting Lives with Precision Medicine
At Strand, genetic testing is available for rare diseases, hereditary cancer predisposition, tumor profiling (somatic cancer testing) for targeted treatment decisions, as well as liquid biopsy for monitoring cancer, knowing drug effectiveness, detecting drug resistance, and knowing cancer status after surgery or treatment. We are very conscious of the work we do here at Strand because of the impact our tests can have on a patient’s quality of life. We are extremely grateful to the patients (like Dimple Bawa pictured here) and doctors who choose to share their gene stories, so more patients and families can benefit from the knowledge that precision medicine has indeed arrived in India and is available to everyone. Read their stories on our website.
Gene Talk – with Dr. Gurdeep Sethi
Dr. Gurdeep Sethi is the Founder of Millennium Cancer Center, Gurgaon, India. Dr. Sethi brings with him more than 26 years of expertise in cancer care and disease management including palliative care, pain management and patient advocacy. He is an active member of the American College of Physicians, American Society of Clinical Oncology, American Society of Hematology, Indian American Cancer Association, Texas Medical Association, Harris County Medical Association, Punjab Medical Council, Delhi Medical Council and Thai Medical Council. He has also served as the Director of Medical Oncology for Pan International Oncology cancer centers in India for the last 16 months after having practiced for over 26 years in the United States of America.
In this short interview, Dr. Sethi shares his views on the clinical utility and implementation of genetic analyses in cancer care in India.
Strand LS: How do you see genomics and genetic analyses playing a role in cancer therapy, in India?
Dr. Sethi: Genomics and genetic analysis is the most effective way to manage cancer not only in India, but also across the globe. This is already being routinely implemented in the U.S. Cracking the human genome code was a gigantic task that took over 10 years, with billions of dollars spent on it. It is our duty to make it useful for everyone. Currently hereditary cancers are seen in approximately 10% of the population. These are cancers that occur in patients less than 50 years age group. We see a very strong shift in the trend of an increased incidence of cancer in the younger population in India. I truly believe that there is a greater prevalence of hereditary cancers in this country as compared to the rest of world. The section of the population that is at risk for hereditary cancer will certainly benefit from germline genetic analysis. Ad hoc genetic testing, done before the actual incidence of cancer can help to increase surveillance. This is expected to lead to early detection of cancers as well as personalized treatment.
Strand LS: Dr. Sethi, In your clinical practice, how has your experience with targeted therapeutics been? Do patients experience a better quality of life with targeted therapeutics than with generic chemotherapy?
Dr. Sethi: With genetic testing we can understand the genetic profile of the cancer. This knowledge leads to choice of targeted drugs that are designed to counter the cellular functions of the mutant proteins. Many patients are already on active chemotherapy sessions. These patients are then reassured in their minds that they Do have alternative directed treatments, if they do not respond to the current treatment regimen. Some patients do shift to the targeted therapy right away due to intolerance to the side effects of chemotherapy. Overall, in the long run I do see targeted therapeutics replacing generic chemotherapy.
Strand LS: Genetic analyses can provide suggestions for off-label uses of targeted therapeutics, based on the identification of genes that they are approved for, although in a different tissue. This is intended to extend therapeutic benefit to patients. What are your views on this matter?
Dr. Sethi: I do believe that there is a great potential for this. However, due to our basic training, we have been conditioned to prescribe medication that has been clinically confirmed to provide therapeutic benefit, as judged from randomized clinical trials. Cancer medicine however is evolving every day. There is much research and data to process and we still do not understand the full potential of genetic analysis and the benefits of targeted therapy based on the gene mutation. In such a scenario, if there is a targeted protein identified with effective medication available, then I would volunteer to treat the patient based on any literature available after they’ve failed conventional treatment options. The process will be explained to the patient in detail and they will be given the choice.
Strand LS: What has been your experience in terms of savings of time and cost to a patient, between targeted and generic chemotherapy?
Dr. Sethi: Chemotherapy has been used in oncology for 50 years. New therapeutic drugs are being developed every year. The side effects are better controlled. Patients are managed better and stay out of the hospital most of the time. The cost of chemotherapy has gone down drastically, over time. Targeted therapy has fewer side effects and lesser collateral damage to normal tissue. The cost, however, is a significant deterrent. It is almost 4 to 5 times the cost of current chemotherapy regimens. As time progresses and these medications become generic, they would replace chemotherapy in the long run.
Strand LS: Dr. Sethi, in your opinion, is a genetic analysis of the tumor essential for therapy choices at the stage of initial diagnosis of cancer or does it work well throughout the course of cancer treatment as well?
Dr. Sethi: Genetic analysis of a tumor can support the choice of therapy at the initial stages of diagnosis as well as throughout the course of cancer treatment. This is absolutely true!! Cancer cells can mutate (change) and present as a disease in multiple variant forms. This essentially means that we need a fresh ‘snapshot’ of the genetic profile of each patient’s cancer, at every stage of the disease. New target proteins are produced due to these mutations. In order to introduce new drugs to target these changes, an understanding of the genetic profile of a cancer – quite like time-lapse photography to capture a sequence of events – is absolutely vital. Liquid biopsy is precisely the technique to use, in order to achieve this. Follow-up liquid biopsy is now becoming a norm as soon as resistance to any current chemotherapy or disease progression are noted.
Strand LS: Liquid biopsy has the potential to provide personalized, longitudinal cancer care to each and every patient. Do you foresee any hurdles or challenges in the inclusion of this new technique for monitoring the progression of cancer, in the Indian scenario?
Dr. Sethi:The challenge I see in this setting is getting the patient to understand the concept in the first place and then accepting increasing cost with the recurring tests. This process of longitudinal cancer care with follow-up liquid biopsies is already a normal practice in the United States. This is because it makes sense, scientifically, and insurance companies cover the cost. In the long run, I agree that liquid biopsy-based personalized cancer therapy will become the norm in India as well.
Stay Ahead of Cancer – Because there is no Time Machine
Cancer, including colon and colorectal cancer, is an ever more present disease in India with the number of cases increasing over the last few years. A key factor in treating and curing cancer is early diagnosis! Unfortunately, we cannot go back in time to undo a cancer diagnosis, but what many don’t realize is that there are regular screening measures and preventive options available today to everyone, but especially so in cases where the risk of disease is higher because of family history. Watch now!