A case-control study on the combined effects of p53 and p73 polymorphisms on head and neck cancer risk in an Italian population.

BACKGROUND: The purpose of this study is to analyze the combined effects of selected p53 and p73 polymorphisms and their interaction with lifestyle habits on squamous cell carcinoma of the head and neck (SCCHN) risk and progression in an Italian population. METHODS: Two hundred and eighty-three cases and 295 hospital controls were genotyped for p53 polymorphisms on exon 4 (Arg72Pro), intron 3 and 6, and p73 G4C14-to-A4T14. Their association with SCCHN was estimated using a logistic regression analysis, while a multinomial logistic regression approach was applied to calculate the effect of the selected polymorphisms on SCCHN different sites (oral cavity, oropharynx, hypopharynx and larynx). We performed an haplotype analysis of the p53 polymorphisms, and a gene-gene interaction analysis for the combined effects of p73 G4C14-to-A4T14 and p53 polymorphisms. RESULTS: We found a significant increased risk of SCCHN among individuals with combined p73 exon 2 G4A and p53 intron 3 variant alleles (OR = 2.22, 95% CI: 1.08-4.56), and a protective effect for those carrying the p53 exon 4-p53 intron 6 diplotype combination (OR = 0.67; 95% CI: 0.47-0.92). From the gene-environment interaction analysis we found that individuals aged < 45 years carrying p73 exon 2 G4A variant allele have a 12.85-increased risk of SCCHN (95% CI: 2.10-78.74) compared with persons of the same age with the homozygous wild type genotype. Improved survival rate was observed among p53 intron 6 variant allele carriers (Hazard Ratio = 0.51 (95% CI: 0.23-1.16). CONCLUSION: Our study provides for the first time evidence that individuals carrying p53 exon 4 and p53 intron 6 variant alleles are significantly protected against SCCHN, and also shows that an additional risk is conferred by the combination of p73 exon 2 G4C14-to-A4T14 and p53 intron 3 variant allele. Larger studies are required to confirm these findings.

A case-control study investigating the role of sulfotransferase 1A1 polymorphism in head and neck cancer.

PURPOSE: Sulfotransferases (SULT) 1A1 detoxify and bio-activate a broad spectrum of substrates including xenobiotics. The SULT1A1 gene possesses a G-->A polymorphism that results in an Arg to His substitution at codon 213, with the His allele having a low activity. The purpose of this study was to evaluate whether SULT1A1 Arg213His polymorphisms are risk factors for head and neck squamous cell carcinoma (SCCHN). METHODS: A total of 124 consecutive primary SCCHN patients and 249 age- and sex-matched hospital controls were enrolled in this study. Genomic DNA was isolated from peripheral blood lymphocytes and genotyping was performed by PCR-RFLP. A comprehensive epidemiological interview was conducted on all participants to collect their lifestyle data. RESULTS: The His/His frequencies in cases and controls were 6.5% (8/123) and 3.6% (9/247), respectively (P=0.049). Multivariate logistic regression analysis showed a significant association of SCCHN and His/His genotype (OR=3.60; 95% CI=1.01-12.88). This association was stronger amongst older people, alcohol and low fruit consumers. The resulted SULT1A1 His/His genotype also associated with a higher risk of neck node positive status (OR=5.82; 95% CI=1.10-30.68). CONCLUSIONS: These preliminary findings show for the first time that the SULT1A1 His (213) allele is a possible risk factor for head and neck cancer development.

Oropharyngoesophageal scintigraphy in the diagnostic algorithm of laryngopharyngeal reflux disease: a useful exam?

OBJECTIVE: To evaluate the role of oropharyngoesophageal scintigraphy in the diagnostic approach to patients with laryngopharyngeal reflux (LPR). STUDY DESIGN: Forty-one patients with chronic laryngopharyngeal symptoms and a control group of 15 healthy volunteers were examined. All subjects underwent standard oropharyngoesophageal scintigraphy. The following parameters were considered: activity-time curves, presence of double peaks and reduced slope in oropharyngeal phase, presence of accelerated or slowed esophagogastric transit, persistence of radioactive material on the pharyngeal or esophageal mucosa, and presence of gastroesophageal reflux (GER) under exercise. RESULTS: There were objective signs of laryngeal reflux in 80.5% of the patients. In 82.9%, scintigraphy documented several associated morphofunctional pathologic patterns: positive GER test (61.0%), presence of double peaks (36.6%), indirect signs of pharyngoesophageal inflammation (31.7%), hypotonic lower esophageal sphincter (17.1%), and slowed esophageal clearance (9.8%). CONCLUSIONS: Oropharyngoesophageal scintigraphy may be used as preliminary examination in outpatients with signs and symptoms of LPR. Cases of classic gastroesophageal reflux disease could be separated from those of LPR disease and therefore submitted to more invasive instrumental examinations.

Postlaryngectomy pharyngocutaneous fistula: incidence, predisposing factors, and therapy.

OBJECTIVE: The pharyngocutaneous fistula (PCF) is a serious complication after total laryngectomy, and its etiology is not well understood yet. The aim of our study was to evaluate predisposing factors, incidence, and management of this complication. STUDY DESIGN AND SETTING: This was a retrospective study of 268 patients who underwent total laryngectomy in our clinic (January 1990-December 2001). A number of factors potentially predisposing to PCF formation were evaluated. RESULTS: A PCF was observed in 16% of patients. Systemic diseases, previous radiotherapy, supraglottic origin of tumor, and concurrent radical neck dissection were significantly associated with PCF. Spontaneous closure was noted in 28 patients, whereas a surgical closure was necessary in 15 patients. CONCLUSIONS: In presence of a specific risk factor, PCF can be expected; nevertheless, its prevention remains very difficult. Moreover, given the high percentage of spontaneous closure, we suggest the "wait and see" approach for 28 days before proceeding with a surgical approach. EBM RATING: C.

CYP1A1, CYP2E1, GSTM1, GSTT1, EPHX1 exons 3 and 4, and NAT2 polymorphisms, smoking, consumption of alcohol and fruit and vegetables and risk of head and neck cancer.

PURPOSE: As risk-modifiers of alcohol and tobacco effects, metabolic genes polymorphisms were investigated as susceptibility candidates for squamous cell carcinoma of the head and neck (SCCHN). METHODS: A total of 210 cases and 245 hospital controls, age and gender matched, were genotyped for CYP1A1, CYP2E1, GSTM1, GSTT1, EPHX1 exons 3 and 4, and NAT2 polymorphisms. A measurement of the biological interaction among two risk factors was estimated by the attributable proportion (AP) due to interaction and its 95% confidence interval (CI). RESULTS: SCCHN risk was associated with high-levels of alcohol intake [OR = 3.50 (95%CI: 1.93-6.35) and OR = 6.47 (95%CI: 2.92-14.35) for 19-30 g/day and >30 g/day, respectively], cigarette smoking [OR = 3.47 (95%CI: 1.88-6.41) and OR = 7.65 (95%CI: 4.20-13.90) for 1-25 and >25 pack-years of smoking, respectively] and low-fruit and vegetables consumption (OR = 2.45; 95%CI: 1.53-3.92). No differences were observed for the genotypes or haplotypes distributions among cases and controls, and no biological interaction emerged from gene-gene and gene-environment interaction analyses. An attributable proportion (AP) due to biological interaction of 0.65 (95%CI: 0.40-0.90) was detected for heavy drinkers with a low intake of fruit and vegetables, and an AP of 0.40 (95%CI: 0.10-0.72) resulted forever smokers with low fruit and vegetables consumption. CONCLUSIONS: Even in presence of high alcohol consumption or cigarette smoking, a high intake of fruit and vegetables might prevent the development of around one quarter of SCCHN cases. The lack of interaction between the studied polymorphisms and the environmental exposures suggests that chronic consumption of tobacco and alcohol overwhelm enzyme defences, irrespective of genotype.