title: COX-2 overexpression and -8473 T/C polymorphism in 3' UTR in non-small cell lung cancer.
abstract: A new class of compounds targeting cyclooxygenase 2 (COX-2) together with other different clinically used therapeutic strategies has recently shown a promise for the chemoprevention of several solid tumors including lung cancer. The aim was to study the possible role of COX-2 -8473 T/C NP and its expression in the pathogenesis of non-small cell lung cancer. One hundred ninety non-small cell lung cancer (NSCLC) patients and 200 healthy age-, sex-, and smoking-matched controls were used for polymorphic analysis, and 48 histopathologically confirmed NSCLC patients were analyzed for COX-2 messenger RNA (mRNA) and protein expression. Our results showed that the frequencies of variant genotypes 8473 CT/CC were significantly less common in the cases (30.0%) than in the controls (36%), suggesting that the 8473 C variant allele is related with lower susceptibility in NSCLC (OR = 0.79, 95% CI 0.54-1.4). However, the frequency of COX-2 -8473 TC and CC genotypes were significantly associated with age in NSCLC (P = 0.02). Quantitative real-time expression analysis showed a significant increase in the COX-2 mRNA in tumor tissues as compared to their adjacent normal tissues [delta cycle threshold (ΔCT) = 9.25 ± 4.67 vs 5.63 ± 3.85, P = 0.0001]. Multivariate logistic regression analyses revealed that the COX-2 expression was associated significantly with age (P = 0.044). Also, an increasing trend was observed in stages I and II and in female patients compared to stages III and IV and male patients, respectively, but no statistical significance was observed. However, COX-2 mRNA expression shown no association with the -8473 C variant allele. Our findings indicate that the COX-2 T8473C polymorphism may contribute to NSCLC cancer susceptibility in the Kashmiri population, while our expression analysis revealed a significant increase of COX-2 in tumor tissues as compared to their adjacent normal tissues, suggesting that it could become an important therapeutic marker in NSCLC in the future.
authors.affiliation: Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir, 190011, India, imty82@gmail.com.
authors.forename: Imtiyaz A
authors.initials: IA
authors.lastname: Bhat
authors.forename: Roohi
authors.initials: R
authors.lastname: Rasool
authors.forename: Iqbal
authors.initials: I
authors.lastname: Qasim
authors.forename: Khalid Z
authors.initials: KZ
authors.lastname: Masoodi
authors.forename: Shabeer A
authors.initials: SA
authors.lastname: Paul
authors.forename: Bashir A
authors.initials: BA
authors.lastname: Bhat
authors.forename: Farooq A
authors.initials: FA
authors.lastname: Ganaie
authors.forename: Sheikh A
authors.initials: SA
authors.lastname: Aziz
authors.forename: Zafar A
authors.initials: ZA
authors.lastname: Shah
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics*; D015153:Blotting, Western; D018287:Carcinoma, Large Cell / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D016022:Case-Control Studies; D015331:Cohort Studies; D051546:Cyclooxygenase 2 / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D020413:3' Untranslated Regions; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human
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