Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.679140
Title: COX-2 inhibitors in oesophageal cancer
Author: Ranka, Satish
ISNI:       0000 0004 5371 2925
Awarding Body: University of East Anglia
Current Institution: University of East Anglia
Date of Award: 2014
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Abstract:
Introduction and Aims: The incidence of Oesophageal cancer (OC) has doubled in the last three decades and is increasing. Due to their poor outcome, strategies are being devised to prevent this disease and look into any association between pre-existing risk factors and medications which may aggravate them. Non-steroidal anti-inflammatory drugs (NSAIDs) may be protective by inhibiting Cycloxygenase-2 (COX-2), an enzyme known to induce malignant transformation in cells. Bronchodilators and Calcium channel blockers (CCB's) that relax the Lower oesophageal sphincter (LOS) may increase Gastro-Oesophageal reflux (GORD) and the risk of Oesophageal adenocarcinoma (OAC). Hence I carried out a case control study looking into any association between ingestion of NSAIDs and drugs which may relax the lower oesophageal sphincter and oesophageal cancer. Case-control study: Methods: 411 patients in Norfolk, with a primary neoplasm of the oesophagus or cardia were matched with 1644 controls with non-melanotic skin lesions. Data on the use of NSAIDs, bronchodilators and CCB's was collected. Results: Compared to nonusers, individuals who used NSAIDs had a significantly reduced risk of oesophageal cancer. Use of NSAIDs was associated with approximately 60-70% reduction in OC. The odds ratios (OR) and 95% Confidence Intervals (CI) for different NSAIDs are as follows Aspirin: 0.38, (0.27-0.54); other NSAIDs: 0.29, (0.19-0.41) and COX-2 Blockers (Coxibs) 0.35, (0.16-0.78). LOS relaxing drugs were consumed more frequently in cases of OC as compared to the controls. Other NSAIDs include propionic acid, acetic acid, enolic acid and fenamic acid derivatives. The OR for LOS relaxing drugs are: Inhaled bronchodilators 3.2 (95% CI 2.2 to 4.7), Theophylline 1.9 (95% CI 1.3 to 5.1) and Calcium channel 12 blockers 2.4 (95% CI 1.2 to 5.0). Data was adjusted for confounding factors like smoking and alcohol consumption. Unadjusted data showed lower negative association with NSAIDs and positive association with drugs which relax the LOS. Conclusion: NSAIDs were protective against OC development while drugs that relax LOS were associated with increased risk in this case-control study. Furthermore, data unadjusted for smoking and alcohol show reduced effect implying smoking and alcohol consumption may be confounding factors. However, due to the undesirable side effects of synthetic COX-2 inhibitors, efforts are now directed towards finding natural compounds which have COX-2 inhibiting or antioxidant properties. Hence I conducted another study of validating a food frequency questionnaire with urinary excretion of quercetin, a naturally occurring Cox-2 inhibitor and naringenin, an antioxidant. With this validation, it would be possible to measure the dietary intake of these compounds in an individual’s diet and recommend dietary changes by conducting further studies. Flavonoid study: Methods: A food frequency questionnaire (FFQ) was used to estimate daily intake of quercetin and naringenin in 49 healthy volunteers. They also provided five 24-hour urine samples over a 2 week period while completing the FFQ. Urinary excretion of quercetin and naringenin was determined by solid phase extraction and high-pressure liquid chromatography. Results: The estimated mean intake of quercetin and naringenin was 29.4 mg (SD 15.0) and 58.08 mg (SD 62.76) per day respectively. Mean urinary excretion of quercetin was 60.1 g (SD 33.1) and naringenin was 0.56 mg (SD 0.42) per 24hrs. The correlation between FFQ-estimated intake and levels excreted in the 24hr urines 13 for quercetin was r = 0.82 (p< 0.0001) and for naringenin was r = 0.251 (p=0.05) respectively. Conclusion: There was a statistically significant correlation between intake and excretion of quercetin and naringenin. Hence, a FFQ may be used as a tool in epidemiological studies requiring an estimate of naturally occurring COX-2 inhibitors or other chemicals following its validation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.679140  DOI: Not available
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