title: Distinct involvement of 9p21-24 and 13q14.1-14.3 chromosomal regions in raw betel-nut induced esophageal cancers in the state of Meghalaya, India.
abstract: BACKGROUND
  Raw betel nut (RBN) chewing is an important contributing factor for esophageal squamous cell carcinoma (ESCC), although associated genomic changes remain unclear. One difficulty in assessing the effects of exclusively RBN induced genetic alterations has been that earlier studies were performed with samples of patients commonly using tobacco and alcohol, in addition to betel-quid. Both CDKN2A (at 9p21) and Rb1 gene (at 13q14.2) are regarded as tumor suppressors involved in the development of ESCC. Therefore, the present study aimed to verify the RBN's ability to induce ESCC and assess the involvement of CDKN2A and Rb1 genes.
  
  
  METHODS
  A panel of dinucelotide polymorphic markers were chosen for loss of heterozygosity studies in 93 samples of which 34 were collected from patients with only RBN-chewing habit. Promoter hypermethylation was also investigated.
  
  
  RESULTS
  Loss in microsatellite markers D9S1748 and D9S1749, located close to exon 1β of CDKN2A/ARF gene at 9p21, was noted in 40% ESCC samples with the habit of RBN-chewing alone. Involvement of a novel site in the 9p23 region was also observed. Promoter hypermethylation of CDKN2A gene in the samples with the habit of only RBN-chewing alone was significantly higher (p=0.01) than Rb1 gene, also from the samples having the habit of use both RBN and tobacco (p=0.047).
  
  
  CONCLUSIONS
  The data indicate that the disruption of 9p21 where CDKN2A gene resides, is the most frequent critical genetic event in RBN-associated carcinogenesis. The involvement of 9p23 as well as 13q14.2 could be required in later stages in RBN-mediated carcinogenesis.
authors.affiliation: Molecular Genetics Laboratory, Department of Biotechnology and Bioinformatics, North-Eastern Hill University, Shillong, India.
authors.forename: Avdhesh K
authors.initials: AK
authors.lastname: Rai
authors.forename: Allen J
authors.initials: AJ
authors.lastname: Freddy
authors.forename: Atanu
authors.initials: A
authors.lastname: Banerjee
authors.forename: Sillarine
authors.initials: S
authors.lastname: Kurkalang
authors.forename: Gordon M
authors.initials: GM
authors.lastname: Rangad
authors.forename: Mohammad
authors.initials: M
authors.lastname: Islam
authors.forename: Henry B
authors.initials: HB
authors.lastname: Nongrum
authors.forename: Hughbert
authors.initials: H
authors.lastname: Dkhar
authors.forename: Anupam
authors.initials: A
authors.lastname: Chatterjee
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001114:Areca / Q000009:adverse effects*; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000235:genetics*; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D019175:DNA Methylation; D004938:Esophageal Neoplasms / Q000209:etiology* / Q000235:genetics*; D019942:Genes, p16; D006801:Humans; D007194:India; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D016160:Retinoblastoma Protein / Q000235:genetics*
chemical_list: D016160:Retinoblastoma Protein