title: Influence of genetic polymorphisms on frequency of micronucleated buccal epithelial cells in leukoplakia patients.
abstract: Micronuclei (MN) are extensively used as an indicator of chromosomal damage and early biomarker of cancer risk. The genetic host factors are known to influence the level of chromosomal alterations consequently affecting MN frequencies. Hence, in the present study, we investigated the extent of chromosomal damage by analyzing micronucleated cell (MNC) frequency in exfoliated buccal epithelial cells (BEC) and its possible relationship with genetic polymorphisms in patients with oral leukoplakia (OL). The study group comprised of habit-free (NHC, n=39), habit controls (HC, n=62) and OL patients (n=66). Micronucleus assay was carried out to determine the MNC frequency and the genotyping was performed by PCR-RFLP for metabolizing (CYP1A1, GSTM1, GSTT1, GSTP1) and DNA repair (hOGG1, XRCC1, XPD) genes. The correlation between MNC frequency and genetic polymorphisms was analyzed. We found significant increase in overall MNC frequency in OL patients as compared to habit-matched controls (p=0.01). The higher proportion of multiple micronucleated cells (>5 MN per cell) indicate increased DNA damage in the buccal mucosa of OL patients than the controls (p=0.004). The polymorphic alleles of XPD751 and hOGG1 showed significant association with total MNC frequency in OLs (p=0.034 and p=0.03 respectively). In conclusion, the extent of chromosomal damage in target tissues is higher in patients with OL. MNC frequency in combination with genetic polymorphisms in DNA repair genes may serve as better predicator of risk.
authors.affiliation: Cancer Research Institute, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai-410210, India. mmahimkar@actrec.gov.in
authors.forename: Manoj B
authors.initials: MB
authors.lastname: Mahimkar
authors.forename: Tanuja A
authors.initials: TA
authors.lastname: Samant
authors.forename: Sadhana
authors.initials: S
authors.lastname: Kannan
authors.forename: Tejas
authors.initials: T
authors.lastname: Patil
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D004249:DNA Damage; D004260:DNA Repair; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D007972:Leukoplakia, Oral / Q000235:genetics* / Q000473:pathology; D008297:Male; D048629:Micronuclei, Chromosome-Defective; D015162:Micronucleus Tests; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology; D011110:Polymorphism, Genetic / Q000235:genetics; D011237:Predictive Value of Tests; D055815:Young Adult
chemical_list: D005982:Glutathione Transferase