title: Evidence for possible non-canonical pathway(s) driven early-onset colorectal cancer in India.
abstract: Two genetic instability pathways viz. chromosomal instability, driven primarily by APC mutation induced deregulated Wnt signaling, and microsatellite instability (MSI) caused by mismatch repair (MMR) inactivation, together account for >90% of late-onset colorectal cancer (CRC). Our understanding of early-onset sporadic CRC is however comparatively limited. In addition, most seminal studies have been performed in the western population and analyses of tumorigenesis pathway(s) causing CRC in developing nations have been rare. We performed a comparative analysis of early and late-onset CRC from India with respect to common genetic aberrations including Wnt, KRAS, and p53 (constituting the classical CRC progression sequence) in addition to MSI. Our results revealed the absence of Wnt and MSI in a significant proportion of early-onset as against late-onset CRC in India. In addition, KRAS mutation frequency was significantly lower in early-onset CRC indicating that a significant proportion of CRC in India may follow tumorigenesis pathways distinct from the classical CRC progression sequence. Our study has therefore revealed the possible existence of non-canonical tumorigenesis pathways in early-onset CRC in India.
authors.affiliation: Laboratory of Molecular Oncology, Centre for DNA Fingerprinting and Diagnostics (CDFD), Nampally, Hyderabad, India.
authors.forename: Ratheesh
authors.initials: R
authors.lastname: Raman
authors.forename: Viswakalyan
authors.initials: V
authors.lastname: Kotapalli
authors.forename: Raju
authors.initials: R
authors.lastname: Adduri
authors.forename: Swarnalata
authors.initials: S
authors.lastname: Gowrishankar
authors.forename: Leena
authors.initials: L
authors.lastname: Bashyam
authors.forename: Ajay
authors.initials: A
authors.lastname: Chaudhary
authors.forename: Mohana
authors.initials: M
authors.lastname: Vamsy
authors.forename: Sujith
authors.initials: S
authors.lastname: Patnaik
authors.forename: Mukta
authors.initials: M
authors.lastname: Srinivasulu
authors.forename: Regulagadda
authors.initials: R
authors.lastname: Sastry
authors.forename: Subramanyeshwar
authors.initials: S
authors.lastname: Rao
authors.forename: Anjayneyulu
authors.initials: A
authors.lastname: Vasala
authors.forename: NarasimhaRaju
authors.initials: N
authors.lastname: Kalidindi
authors.forename: Jonathan
authors.initials: J
authors.lastname: Pollack
authors.forename: Sudha
authors.initials: S
authors.lastname: Murthy
authors.forename: Murali
authors.initials: M
authors.lastname: Bashyam
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002471:Cell Transformation, Neoplastic; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D042241:Early Diagnosis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D007194:India; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D051153:Wnt Proteins / Q000378:metabolism*; D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins