Approved Research

Prioritization of predictive gene candidates for selected phenotypes in Indian ethnic population for prospective evaluation in a genetic association study in children with acute lymphoblastic leukemia

Lay summary

Acute lymphoblastic leukemia is the most commonly type of cancer in children. In high income countries, affected children have a good chance of recovering. However, in countries such as India, the probability of long-term survival is much lower. The reasons for this difference are multi-factorial including poorer health care access resulting in later diagnosis, treatment interruption, relapse and death resulting from adverse drug reactions or infections. Indeed, drugs used to treat leukemia are often harsh and responsible for a wide range of negative or adverse effects called treatment related toxicities.

The gap between a sufficient drug exposure to avoid disease recurrence and an excessive dosage resulting in toxicity is narrow and treatment success depends on many different parameters including inherited genetic characteristics. Pharmacology is the study of how drugs act on biological systems and how the body responds to the treatment, both in terms of efficacy and safety. Sometimes, large inter-individual differences in treatment response can be observed resulting from a combination of environmental, clinical, and genetic characteristics specific to each patient. Since genetic variants segregate at various frequencies in different human populations, genetic markers of drug response and adverse effect susceptibility might be specific to the Indian population.

We are currently participating in an observational study, aiming to identify genetic determinants of acute lymphoblastic leukemia treatment response and toxicity in Indian children. The fundamental goal of the study is to optimize treatment selection and dosage according to the intrinsic characteristics of each patient, formulate population-specific therapeutic recommendations and identify the most relevant risk factors for various treatment related outcomes.

There is a large dataset in the UK biobank repository representing the Indian community living in the United Kingdom. We plan to use this dataset to describe the genetic profile of the Indian population with respect to drug pharmacology and explore the relationship between genetic polymorphisms present in the Indian population and clinical or biological parameters used to assess treatment-related toxicities.