The importance of genetic testing4 min read . Updated: 28 Dec 2017, 02:03 AM IST
With genetic analysis, a person can benefit from timely interventions and gene-targeted treatments.
On all counts, tobacco smoke is a killer. It contains over 60 carcinogenic chemicals, which makes smoking the most important risk factor for lung cancer. Smoking can also cause various other cancers, including those of the tongue, mouth, throat, nose, nasal sinus, voice box, stomach, liver, and the bone marrow. Yet, Winston Churchill lived a fulfilling life of 91 years—in spite of smoking 10 cigars a day and even led England through World War II successfully. Churchill seems to be one of those to have been spared the deleterious and carcinogenic effect of smoking. But why?
The case of Churchill and other similar instances make us question the genetic component in the reduced risk and protective association to cancers in heavy smokers.
Certain genetic variations in the GPX1 (Glutathione peroxidase) and EPHX1 (Epoxide hydrolase) genes are among the few that have been studied by researchers.
In fact, most cancers known to mankind have already been genetically mapped and exploited for developing new forms of treatment and targeted therapies—Angelina Jolie’s example being a case in point.
Disease mapping and associations
Most diseases involve complex interactions of the involved genes, in addition to environmental stimuli. It is possible that a healthy-born individual runs a high risk of acquiring a deadly disease. This is known as genetic predisposition or susceptibility. Even though genetically predisposed individuals may lead a healthy lifestyle, they have an inherent risk of contracting a disease, independent of environmental factor, unless the risk factors are properly addressed. Advancement in genetic research and testing have aided our understanding and helped us in mapping the disease at the molecular level through genetic associations.
Consider diabetes, for one. Accounting for almost 90% of all diabetes-affected individuals, Type II Diabetes Mellitus (T2DM) is partly known to be inherited. According to studies by the World Health Organization (WHO), first degree relatives of T2DM patients are about three times more susceptible to T2DM than individuals without a positive family history of the disease. Thus, the first step in identifying the disease-susceptibility genes should involve identification of candidate genes. Candidate genes for T2DM include genes responsible for pancreatic cell (Beta cell), insulin action/glucose metabolism, or other metabolic conditions that increase T2DM risk (eg, energy intake/expenditure, lipid metabolism). More than 50 candidate genes for T2DM have been studied worldwide.
Role of population genetics and epigenetics
Genetic mapping has proved to be effective in disease-risk prediction. It is a stepping stone to advanced diagnostics and targeted treatments. Studies show that variations which are pathogenic in one ethnic group are not so in others. This makes the role of population genetics extremely vital. Simply put, population genetics is the study of genetic variation within populations and assessment of changes in the frequencies of genetic variations and alleles in populations. Alleles are nucleotide bases (A, T, G and C) found in the DNA in different combinations and demonstrate genetic variations. These alleles collectively form a cluster known as the gene pool of a certain population. The genetic composition of a population’s gene pool changes over time owing to mutation and other factors.
Today, we are well-equipped with cost-effective technology, combined with increased awareness about the role of heredity and genetics in our lives. The increase in genomic data in recent years has enabled us to conduct more association studies, thus fortifying genetic research.
Studies have also directed us towards epigenetics, which has become popular in recent years. Although we inherit genetic material from our parents, it is at times reshaped by certain epigenetic alterations—influencing (silencing or over-expressing) the activity of certain genes. Epigenetics is the study of the effect of environmental factors on the modification of gene expression and the subsequent changes in organisms. It describes the factors controlling genetic expression, apart from an individual’s DNA sequence.
A relatively new reckoning
The term ‘epigenetics’ has garnered a lot of attention only recently, in spite of having surfaced almost a century ago. In the past year or two, evidence from epigenetic studies has been very conclusive, and some might even say that rapidly growing acceptance of epigenetics is a big step forward. According to Toshikazu Ushijima from the carcinogenesis division of Japan’s National Cancer Centre Research Institute, epigenetic mechanisms—which account for one-third to one-half of known genetic alterations—are among the five most important considerations in the field of cancer research and treatment.
However, many researchers believe we are far away from getting any real answers. According to Randy Jirtle, professor of radiation oncology at Duke University Medical Centre, “We’ve done virtually nothing so far. I’m biased, but the tip of the iceberg is genomics and single-nucleotide polymorphisms. The bottom of the iceberg is epigenetics."
Epigenetic changes are responsible for normal development and health, and many diseases, too. This makes epigenetics a promising field of research for further data and applications in the near future.
Why do we need genetic testing
Numerous disease conditions still cannot be properly diagnosed with contemporary methods. With genetic analysis, a person can benefit from timely interventions and gene-targeted treatments. Precision medicine is also emerging to provide better and effective treatment. Further, reducing the trial-and-error in lifestyle choices—nutrition plans and fitness regimes—are among the key benefits of genetic assessments.
I’m against the over-promise that people are going to see healthcare becoming completely different in a few years in India. But it will be fundamentally different. We will have diagnostics and treatments that are far more effective—resulting in people living normal lifespans with enhanced quality.
Pranav Anam is co-founder of The Gene Box, a genetics-based healthcare platform.