Spectrum of mutations in genes associated with familial colorectal cancer syndrome (MLH1, MSH2, PMS2, MSH6, and APC): A not so common hereditary cancer syndrome in Indian population

Indian J Gastroenterol. 2020 Dec;39(6):599-607. doi: 10.1007/s12664-020-01096-x. Epub 2020 Nov 16.

Abstract

Incidence of colorectal cancer (CRC) is lower in India than in other parts of the world. Approximately 5% to 10% of CRC is inherited. Hereditary non-polyposis colorectal cancer (HNPCC) syndrome and familial adenomatous polyposis (FAP) syndrome are the two known familial cancer syndromes of gastrointestinal tract, which occur due to inherited genetic predisposition. Not much is known about the molecular profile of families with inherited CRC syndromes seen in Indian population. At our institute, we have been providing genetic testing and counseling service to all the families referred to us with suspicion of inherited cancer predisposition syndrome. We analyzed 36 suspected families at our clinic. Personal and family history of cancer was obtained from the proband and appropriate genetic testing was performed in 19 patients (13 with HNPCC, 5 with FAP, and 1 with Cowden syndrome). We present here our experience and spectrum of pathogenic variants observed in this patient cohort and review on published studies describing molecular profile of Indian patients with CRC syndromes.

Keywords: Cancer surveillance; Colonic polyp; Colorectal cancer; Familial adenomatous polyposis; Hereditary cancer syndrome; Hereditary non-polyposis colorectal cancer; India.

MeSH terms

  • Adenomatous Polyposis Coli Protein / genetics*
  • Asian People / genetics
  • Cohort Studies
  • Colorectal Neoplasms / diagnosis
  • Colorectal Neoplasms / epidemiology
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / prevention & control
  • DNA-Binding Proteins / genetics*
  • Female
  • Genetic Counseling
  • Genetic Predisposition to Disease / genetics*
  • Genetic Testing
  • Humans
  • Incidence
  • India / epidemiology
  • Male
  • Mismatch Repair Endonuclease PMS2 / genetics*
  • MutL Protein Homolog 1 / genetics*
  • MutS Homolog 2 Protein / genetics*
  • Mutation / genetics*
  • Syndrome

Substances

  • APC protein, human
  • Adenomatous Polyposis Coli Protein
  • DNA-Binding Proteins
  • G-T mismatch-binding protein
  • MLH1 protein, human
  • PMS2 protein, human
  • MSH2 protein, human
  • Mismatch Repair Endonuclease PMS2
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein