Of hidden cancer and inherited disorders
Welcome to the first issue of myStrand in 2018! We start the new year reflecting on the silence and stigma in India surrounding January’s cancer on the health awareness calendar and the why a genetic diagnosis is so important when facing inherited disorders. Write to us at firstname.lastname@example.org with your questions and topic suggestions. We would like to hear from you!
The myStrand Team!
What is this month’s cancer?
Dedicating a month to raising awareness for a particular health issue has been a very nice social trend for a while and some countries use the strategy more than others. For example, October is Breast Cancer Awareness Month and many activities, including our own ‘Spread Pink. Spread Courage’ campaign focused on organized events in that month only. So, I ask you, which cancer is the focus of attention at the start of a new year in the Gregorian calendar, January that is? Well, I’ll be honest, even we had to look it up for a distinct lack of reporting and social media coverage in India made sure it wasn’t obvious.
January is dedicated to HPV and cervical cancer awareness. HPV stands for Human Papilloma Virus and this virus is what makes cervical cancer (and the other cancers that can be caused by the same virus, including penile cancer in men, and cancer of the anus, mouth and throat in both men and women) stand out from other cancers. While there are other risk factors for all these cancers, the strongest predictor for getting cervical cancer is being infected with HPV, which an estimated 10% of Indian women are. That makes it a fairly common infection and this is true not just in India, but across the world.
What is different in India though is that a large number of women still die from cervical cancer despite the fact that in today’s world, this particular cancer is entirely preventable and completely treatable when detected in the early stages through one of the many screening options. According to GLOBOCAN 2012 data, one quarter of all cervical cancers globally are registered in India (and that does not factor in the known issue of under-reporting in India). Cervical cancer is one of the leading causes of cancer mortality in Indian women aged 30-69 years accounting for 17% of all cancer deaths in that age group. In real numbers, this means up to an estimated 150,000 Indian women are diagnosed with cervical cancer every year and around half, some 75,000 women die of the disease.
So, we know that cervical cancer is a killer and we know it can be prevented through regular screening. This begs the question, why are so many women still diagnosed at the later stages of disease and therefore still dying in such large numbers? For one, most Western countries have achieved the much lower incidence rate of 1 in 100 women, compared to India’s 1 in 53 women through national screening programmes. India’s lack of public healthcare infrastructure, especially in rural areas, and a lack of centralized health policy make it close to impossible to implement such a screening programme. Localized efforts by non-governmental agencies or corporate sponsored foundations, like Strand Life Foundation in co-operation with Cancer Care India or the Biocon Foundation offer free low tech screening, sometimes even with follow-up testing and treatment, but their reach is far too small to make a nationwide impact.
More critical still, even in urban areas, where screening is routinely offered by hospitals and clinics, the lack of awareness of what causes cervical cancer and that screening is very effective at preventing the cancer in the first place, means many women who have access to screening still don’t get it done. A culture of taboo and silence surrounding most female issues, including breast, ovarian, and cervical cancer, prevents even many an educated woman from seeking advice and going for their check-ups at the recommended intervals. For cervical cancer, the screening procedure really isn’t a big deal. A simple Pap smear done every 3 years is all it takes to stay ahead of this cancer. For rural areas, where even a Pap smear would be considered hi-tech and too expensive, there are other effective screening methods that can be taught to primary healthcare providers. These health workers can identify women bearing pre-cancerous lesions and refer them to urban centers for treatment. An even newer method to detect the presence of HPV itself, before any changes have occurred in the cervical tissue, is also available in major cities, albeit at a higher cost. However, a negative result can increase the screening interval to 5 years, while a positive result can keep you and your healthcare team on alert to follow up with more frequent Pap smears and encourage you to minimize other risk factors.
However, it is important to bear in mind that not all women who are infected with HPV go on to develop cervical cancer. There are many other risk factors that increase the chances of getting cervical cancer, including smoking, long term use of oral contraceptives, obesity, poor diet lacking fresh fruits and vegetables, a weakened immune system caused by HIV infection or medication that suppresses the immune system, among others.
If you would like to find out more about cervical cancer causes, screening, and treatment, we recommend the following online sources:
National Cervical Cancer Coalition – 10 Things to know about HPV and Cervical Cancer: http://www.nccc-online.org/images/pdfs/10ThingsHPV_CCAM.pdf
American Cancer Society – Cervical Cancer: https://www.cancer.org/cancer/cervical-cancer.html
Web MD – What increases your risk for cervical cancer?: https://www.webmd.com/cancer/cervical-cancer/cervical-cancer-what-increases-your-risk
Disclaimer: The information provided in this article is in no way intended to replace expert medical advice. Always discuss any concerns with your doctor.
Clinical Exome vs Whole Exome Testing
Talking about all the different ‘omes’ has left the scientific circles and entered the mainstream with the genome, the microbiome, and maybe even the proteome doing the rounds in social circles. The genome is what lies at the heart of genetic testing and the so-called reference genome is what an average healthy organism’s genome looks like. So when we are looking for the culprit in a particular genetic disease, we sequence the patient’s genome and compare it with that reference genome to identify so-called genetic mutations that are attributed to causing the disease. This is where we enter the ‘looking for a needle in a hay stack’ analogy and that is also where the ‘exome’ takes center stage.
The human exome refers to the roughly 1% of the human genome that is responsible for making the proteins that our body needs to function. Now, that may sound like a huge reduction in the size of our haystack, but we are still looking at a very large haystack when it comes to the cost of sequencing this ‘whole exome’ and analyzing the information gleaned from it. However, modern computer technology has allowed us to build databases of all the research and clinical observations of relationships between our genes and diseases. Such databases have enabled us to narrow down the list of genes we could investigate when looking for a culprit in the large majority of genetic diseases a doctor might be presented with. This, now much smaller, portion of our genome is called the ‘clinical exome’. Such smaller ‘clinical exome’ tests are much more economical for patients and typically enable accurate differential diagnoses between conditions with multiple overlapping symptoms. You can read more about just such a case in the second article of this issue of myStrand.
Why a genetic diagnosis for inherited disorders matters
No two people are the same, not even twins, thanks to the healthy variety nature has created over the years in our genomes. The vast majority of this variation contributes to our survival as a race and has only a minor impact on our health and lifespan. Yet, every now and then, a mutation in the ‘recipe book’ that is our genome, be it a single letter or a whole ‘ingredient’, causes serious health concerns that can manifest in newborns, young children, and sometimes only in adulthood. Such diseases are commonly known as ‘Inherited Disorders’ because, more often than not, the mutation was inherited from one or both parents.
Example of dominant inheritanceThere are several types of inheritance seen in nature. The type of inheritance depends on which chromosomes bear the new mutation (genetic variation) as well as on whether one or both copies of a gene need to be mutated to be effective in the person. Now, if we go back to our school biology classes, we learnt that we have two copies each of 21 chromosomes and two sex chromosomes: two X chromosomes for girls, one X and one Y chromosome for boys. If a condition is caused by a genetic mutation sitting on one of the 21 chromosomes, the mode of inheritance is referred to as Autosomal and if the mutation is located on one of the sex chromosomes, it is called either X-linked or Y-linked inheritance. So, with the exception of genes on the sex chromosomes, we all have two copies (a pair) of each gene. Next, geneticists distinguish between dominant and recessive inheritance. If a condition is inherited in a dominant fashion, a variant (or mutated) gene present on one of the chromosomes is sufficient to trigger the onset of an inherited disorder. If a condition is inherited in a recessive mode, then the same gene mutation has to be present on both copies of the chromosome to cause any health problems. Depending on which type of inheritance a disorder follows, it is either inherited only from the father, only from the mother, or both parents. Furthermore, some disorders are caused by genetic mutations in mitochondrial DNA, which can only be passed on by the mother.
Pattern of inheritance (partially reproduced from Genetics Home Reference)
|Autosomal dominant||One mutated copy of the gene in each cell is sufficient for a person to be affected by an autosomal dominant disorder. In some cases, an affected person inherits the condition from an affected parent.||Huntington disease, Marfan syndrome|
|Autosomal recessive||In autosomal recessive inheritance, both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. Autosomal recessive disorders are typically not seen in every generation of an affected family.||cystic fibrosis, sickle cell disease|
|X-linked dominant||X-linked dominant disorders are caused by mutations in genes on the X chromosome, one of the two sex chromosomes in each cell. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell is sufficient to cause the disorder. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes the disorder. In most cases, males experience more severe symptoms of the disorder than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons (no male-to-male transmission).||fragile X syndrome|
|X-linked recessive||X-linked recessive disorders are also caused by mutations in genes on the X chromosome. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons (no male-to-male transmission).||hemophilia, Fabry disease|
|Y-linked||A condition is considered Y-linked if the mutated gene that causes the disorder is located on the Y chromosome, one of the two sex chromosomes in each of a male’s cells. Because only males have a Y chromosome, in Y-linked inheritance, a mutation can only be passed from father to son.||Y chromosome infertility, some cases of Swyer syndrome|
|Codominant||In codominant inheritance, two different versions (alleles) of a gene are expressed, and each version makes a slightly different protein. Both alleles influence the genetic trait or determine the characteristics of the genetic condition.||ABO blood group, alpha-1 antitrypsin deficiency|
|Mitochondrial||Mitochondrial inheritance, also known as maternal inheritance, applies to genes in mitochondrial DNA. Mitochondria, which are structures in each cell that convert molecules into energy, each contain a small amount of DNA. Because only egg cells contribute mitochondria to the developing embryo, only females can pass on mitochondrial mutations to their children. Conditions resulting from mutations in mitochondrial DNA can appear in every generation of a family and can affect both males and females, but fathers do not pass these disorders to their daughters or sons.||Leber hereditary optic neuropathy (LHON)|
These inheritance patterns became known through Gregor Mendel’s experiments with peas and other organisms (hence inherited disorders are sometimes also referred to as Mendelian disorders) in the 18th century and later, in the early 19th century, widely accepted by science and society. As a result, marrying within the same family (especially first- and second-degree cousins) was actively discouraged or even legally forbidden because it increased the chances of bearing children with such often devastating and fatal disorders. However, inter-family or consanguineous marriage is still practiced in many communities across the world and remains prevalent in some Indian states. This fact explains the continued high burden of such disorders in some parts of India.
So why should we be aware of all this? Why is it so important? Well, ever since the advent of next-generation sequencing and the decoding of the whole human genome, we are now able to look at our genes in much greater detail than ever before. With the dwindling cost of sequencing and hence genetic testing, getting a genetic test is going to be a routine affair, much like going in for annual health checkups. Knowing what exactly went wrong at the gene level, rather than arriving at a diagnosis based on symptoms, experience, and recent or anecdotal family history alone, helps doctors today to create effective treatment options for some of these diseases. Genetic tests also give parents the information and tools to plan future pregnancies and help families and young people choose a life partner accordingly.
Genetic testing for inherited disorders is not only possible in children and adults, but can also be performed on DNA from an unborn baby through mother’s blood, amniocentesis, or chorionic villus sampling (CVS) in the early stages of an ongoing pregnancy, depending on the suspected genetic disorder. At Strand we have tested the DNA of many children and their parents to identify the culprits for much heartache and, let’s face it, financial burden due to the ill health of multiple children caused by an inherited condition. You can find some of their stories on our website at http://strandls.com/strand-patient-stories/
If you are in the family way or planning a family and you know of or suspect a genetic condition in your family, discuss this with your doctor who will be able to advise you on the best course of action and refer you for the appropriate tests.
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
The Life in Tech – A short history of Strand in Forbes India
“While not nearly in the billion-dollar league, one Indian biotech venture that did successfully reach the stage where it was ready for a public listing is Strand Life Sciences. It was started in 2000 by scientists from the Indian Institute of Science. One of them, Professor Vijay Chandru, remains Chairman and Managing Director, while another, Dr. Ramesh Hariharan, is now CEO.
“Biotech, with Artificial Intelligence and quantum computing, will redefine human society in the 21st century,” Chandru said while moderating a discussion on biotech as part of a conference organized by Carnegie Endowment in December.”
The company started out with bioinformatics, a meeting point of biology and data analytics, and became a specialist in human gene sequencing technologies. Today, Strand Life Sciences provides genetic testing-based diagnostics in cancer detection and treatment. The company has over 200 scientists and works with more than 300 large hospitals and hospital chains in India. Read more
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