Pre-emptive Germline Testing for Cancer

With over 1.4 million new cancer cases diagnosed each year, India faces a staggering cancer burden. This staggering figure underscores the critical need for robust strategies to tackle cancer comprehensively. In the realm of cancer management, pre-emptive germline testing emerges as a pivotal tool as early detection and diagnosis remain a linchpin in the fight against cancer. As the nation grapples with the scale of cancer incidence, pre-emptive germline paves the way through the transformative pillars of early detection, carrier screening, cascade testing, and pharmacogenomics.

• Early Detection

A significant proportion of people in India carry germline mutations that increase the risk of cancer. These ‘high-risk’ individuals traditionally undergo a battery of tests to identify the culprit genetic cause, involving multiple molecular assays including analyzing chromosomal abnormalities, structural changes, and various mutations – a time-consuming approach. Encompassing all genetic testing in a single comprehensive analysis, whole-genome sequencing (WGS) offers a paradigm shift, promising quicker and more precise results compared to the traditional cascade of tests. By identifying patients harboring high-penetrance mutations associated with certain cancers, we can activate proactive screening and prevention measures. This early detection can potentially save lives by catching malignancies in their earliest stages before they wreak havoc.

Beyond direct testing, genomic analysis helps reveal incidental findings with clinical implications. Around 2-3% of individuals in the general population are estimated to carry such actionable insights, as reported in studies worldwide. The American College of Medical Genetics offers guidelines for reporting these findings, focusing on evidence, actionability, and patient benefit. Currently, they encompass 19 inherited cancer syndromes mapped to 28 genes. 

• Carrier Risk and Cascade Testing

Pre-emptive testing isn’t just about understanding the present; it empowers us to anticipate the future. It reveals if we carry a hidden mutation, silent within ourselves but potentially dangerous for our offspring. Carrying the mutation doesn’t guarantee our own illness, but it can raise the curtain on a higher risk for our children. This is where cascade germline testing also steps in, tracing the genetic domino effect within families. Through cascade germline testing, identifying a specific genetic anomaly in one family member can prompt targeted testing for the same in close relatives. The initial diagnosis triggers targeted assays in blood relatives, pinpointing those who inherited the pathogenic variant. Germline testing in cancer thus unlocks a wealth of possibilities including early detection and prevention, genetic counseling, and informed family planning, thus transforming passive acceptance into proactive control. 

• Prognosis and Treatment

Traditional cancer treatment often resembled throwing darts in the dark. Pre-emptive genomic testing sheds light on this darkness, fuelling the field of pharmacogenomics – the science of how your genes dictate drug response. By aligning treatment with a patient’s genetic signature, we can maximise efficacy while minimizing the often debilitating side effects. This individualised approach promises not only improved survival rates but also a higher quality of life for cancer patients. For instance, before blasting tumours with fluoropyrimidines, a quick check for germline mutations in the DPYD gene can be a lifesaver. This helps identify patients at risk for severe drug toxicity, allowing doctors to adjust doses or choose alternative therapies. It’s a shining example of how pharmacogenomics empowers personalised cancer care, maximizing treatment effectiveness while minimizing harsh side effects.