PEACOCC: Pan-India EArly-onset COlorectal Cancer Consortium

Despite overall decline in annual colorectal cancer (CRC) cases, the incidence of early-onset CRC (EOCRC) has exhibited a significant increase worldwide.

CRC is a well understood cancer; but our learnings are based mainly on studies performed in the West on late-onset CRC (LOCRC).

Genomic profiling of LOCRC has revealed actionable genetic aberrations that are being evaluated for developing targeted therapies. In contrast, EOCRC remains poorly understood, even in the West.

Based on this insight, we commenced genomic profiling of a limited number of EOCRC samples restricted to patient population in Hyderabad, Telangana, more than a decade ago.

Our work did reveal cardinal differences from LOCRC, including reduced Wnt activation, enrichment of Ca2+/NFAT signalling and high frequency of mutations targeting SWI/SNF components.

In this proposal, we propose comprehensive molecular profiling of EOCRC samples collected from various geographical regions of India where incidence and etiology are expected to differ.

We shall catalogue and functionally validate somatic mutations and gene fusions, determine primary de-regulated signalling pathways, identify molecular subtypes, evaluate possible links with microbiome dysbiosis and generate reagents in the form of tumor organoids. The project will likely improve our understanding of EOCRC besides revealing possible therapeutic options.