RESUMEN
AIMS: Cholinergic signaling, particularly in response to non-physiological ligands like nicotine, stimulates carcinogenesis of a variety of tissue types including epithelia of the cervix uteri. Cholinergic signaling is mediated by nicotinic acetylcholine receptors (nAChRs), which are pentamers formed by subsets of 16 nAChR subunits. Recent literature suggests that single nucleotide polymorphisms (SNPs) of some of these subunits, notably alpha5, are risk factors for developing lung cancer in smokers as well as in non-smokers. MAIN METHODS: We have studied the prevalence of four SNPs in the alpha5, alpha9, and beta1 subunits, which are expressed in cervical cells, in 456 patients with cervical cancers, precursor lesions, and healthy controls from two cohorts in Mexico. KEY FINDINGS: A SNP in the alpha9 subunit, the G allele of rs10009228 (alpha9, A>G) shows a significant trend in the combined cohort, indicating that this allele constitutes a risk factor for neoplastic progression. The A allele of the SNP rs16969968 (alpha5, G>A), which correlates with the development of lung cancer, shows a non-significant trend to be associated with cervical lesions. Two other SNPs, rs55633891 (alpha9, C>T) and rs17856697 (beta1, A>G), did not exhibit a significant trend. SIGNIFICANCE: Our study points to a potential risk factor of cervical carcinogenesis with importance for DNA diagnosis and as a target for intervention.
Asunto(s)
Polimorfismo de Nucleótido Simple , Receptores Nicotínicos/genética , Neoplasias del Cuello Uterino/genética , Cuello del Útero/metabolismo , Femenino , Humanos , México/epidemiología , Neoplasias del Cuello Uterino/epidemiologíaRESUMEN
BACKGROUND AND OBJECTIVE: Competency-based training and assessment are increasingly replacing the traditional structure- and process-based model of medical education. The web-based Essential Bronchoscopist (EB) is an open access, laddered, competency-based curriculum of question-answer sets pertaining to basic bronchoscopic knowledge, accessible in five languages. The purpose of this study was to use consensus to evaluate whether question-answer sets (items) from the EB could provide material from which to devise competency-based tests of bronchoscopic knowledge that could be used in countries with different health-care environments. METHODS: Ten junior and five senior bronchoscopists in Argentina and the USA were asked to identify the material in each of the 186 items of the EB as either 'not necessary', 'necessary' or 'absolutely necessary' for inclusion in a competency-based test of bronchoscopic knowledge. The kappa statistic was used to analyse inter-rater agreement. RESULTS: More than 80% of the 30 participants rated 150 of 186 items as necessary or absolutely necessary. Seventy items were rated as absolutely necessary by more than 50% of participants and as necessary or absolutely necessary by more than 90%. There was no statistically significant difference between items selected, based on level of training or environment of practice. CONCLUSION: Consensus among junior and senior bronchoscopists from two culturally different health-care environments demonstrated that question-answer sets from the EB can be used to provide material for competency-based tests of bronchoscopic knowledge.