Genetic biomarker tests shift colorectal cancer screening toward DNA changes in India

Recent advances in genetic science are shifting the focus from detecting indirect signs of cancer, like blood in the stool, to identifying DNA changes directly linked to cancer development in colorectal cancer (CRC). In India, CRC is growing rapidly and is now the fourth most common cancer overall, with more than 64,000 new cases and over 38,000 deaths reported in 2022. CRC cases and mortality have been increasing over the past decade, while many people remain unscreened until late stages.

Genetic screening for early detection of CRC matters for India as the country faces unique challenges in detection and care. There are low screening rates, and accessibility and awareness remain barriers for many communities. A large proportion of CRC patients in India are under the age of 40 years, potentially pointing to lifestyle, genetic, and environmental influences.

Advanced genetic tests include blood-based genetic tests that analyze small fragments of DNA that tumours shed into the bloodstream. These include epigenetic markers, which are chemical changes in DNA that signal abnormal cell behavior of specific genes often present in CRC cells. Stool DNA testing is another approach, because CRC and precancerous polyps shed cells into the digestive tract, allowing molecular tests to detect cancer-associated genetic mutations and methylation patterns in feces.

These tests have higher sensitivity than older stool blood tests and can detect cancer earlier. Standard tools like colonoscopy and fecal occult blood tests have long been the backbone of CRC screening, but colonoscopy requires bowel preparation, a clinic visit, and sedation, which can be barriers for many people. Stool-based tests are easier, but they look for blood, which may not always be present in early-stage disease. Due to these limitations, participation in screening remains low even among at-risk groups in India, with colonoscopy uptake estimated below 10% in real-world settings.

Personalized screening for genetic risk profiling is now available. While most CRCs occur sporadically, a portion are influenced by inherited genetic factors, and certain individuals may carry gene variants that increase their lifetime risk of developing CRC even if they have no symptoms. Advances in genomics are enabling the development of risk scores that combine information from many gene variants to estimate a person’s likelihood of developing CRC.

Today, genetic risk can be evaluated using targeted hereditary cancer gene panels that analyze genes known to be associated with colorectal cancer susceptibility, such as those involved in DNA repair pathways. Multigene panels linked to hereditary colorectal cancer syndromes include APC, MLH1, MSH2, MSH6, PMS2, MUTYH, PTEN, SMAD4, and STK11, and can be used to guide screening and treatment.

Early detection can make treatment easier and less costly. With CRC detected at a local stage, survival rates can be as high as 90%, compared to much lower survival when cancer is found late. Bringing genetic screening into broader public health efforts could also support data initiatives like the Bharat Cancer Genome Atlas and Indian Cancer Genome Atlas (ICGA), which aim to better understand genetic patterns specific to Indian populations and enable population-specific early detection strategies.