Chromosome aberrations in peripheral blood lymphocytes of high-risk HPV-infected women with HGSIL.

Genomic instability is one of the main characteristics of malignant tumors, including HPV-induced cervical cancer. The aim of this study was to explore the use of assessing chromosome aberrations (CA) in peripheral blood lymphocytes as a biomarker for genomic instability in high-risk HPV-infected women with high-grade squamous intraepithelial lesions (HGSIL). A total of 120 women were recruited for this study, following cytology/colposcopy evaluation and HPV DNA detection. The study groups consisted of 30 HPV(+) women with histologically confirmed cervical intraepithelial neoplasia grade 2/3 and 30 HPV(+) women with carcinoma in situ (CIS). Two control groups, including 30 women HPV(-) and 30 women HPV(+), were recruited among women who were reported as cytology negative. Lymphocyte cell cultures were established for 52 hr, and 100 complete metaphase cells were evaluated per subject for CA analysis. The results show that women with CIS had significantly higher frequencies of both aneuploidy (0.67 +/- 0.20 vs. 0.14 +/- 0.08, P = 0.020) and tetraploidy (0.88 +/- 0.23 vs. 0.17 +/- 0.08, P = 0.013) in comparison with HPV(-) controls. These findings suggest the usefulness of peripheral blood lymphocytes to detect genomic instability associated with HPV-induced HGSIL.

Exposure to wood smoke, HPV infection, and genetic susceptibility for cervical neoplasia among women in Colombia.

Cervical cancer is the second leading cause of death from cancer among women in Colombia (16/100,000). Infection with high-risk human papillomavirus (HPV) plays a major role in the etiology of high-grade squamous intraepithelial lesions (HSILs). Exposure to chemical agents may be a cofactor for tumor induction, and individual genetic differences in the metabolism of these chemical agents may affect the susceptibility of individuals towards the development of HSIL. In this case-control study, a total of 91 cases with HSIL and 92 healthy controls, frequency-matched by age and place of origin, were recruited, and their frequencies of CYP2E1, GSTM1, and GSTT1 polymorphism were determined. We then evaluated the association of these polymorphisms, by themselves and in combination with wood smoke exposure and HPV-infection status, with the risk of HSIL. The results indicate that GSTM1 and GSTT1 polymorphism were not associated with HSIL, although a small increase in risk was observed for individuals who were GSTT1 null (OR = 1.4, 95% CI = 0.57-3.44). Contrary to other investigations, the c2/c2 variant of the CYP2E1 gene was associated with a significant increase in risk after adjusting for wood smoke exposure (OR = 6.3, 95% CI = 1.10-36.38) or wood smoke exposure and HPV-infection status (OR = 10.7, 95% CI = 1.76-65.58). Wood smoke exposure also increased the risk of HSIL among CYP2E1 c2/c2 HPV-positive women (OR = 3.3, CI = 0.50-22.50); however, the increase did not achieve statistical significance. Our study provides tantalizing evidence that genetic differences in the metabolism of wood smoke carcinogens, particularly metabolism by CYP2E1, may confer susceptibility for HSIL development. Further investigations with larger populations will be needed to confirm this association, which may provide important information for improving cervical cancer prevention programs.

Chromosome aberrations among cigarette smokers in Colombia.

Worldwide, the annual morbimortality caused by cigarette smoking is a major public health concern. In Colombia, up to 33% of the adult population has smoked at some point in life, raising important national issues on the disease burden from tobacco. The aim of this study was to establish whether cigarette smoking increases the frequency of chromosome aberrations (CA) in peripheral blood lymphocytes of smokers (n = 52) compared with non-smokers (n = 52) in Popayán, Colombia. After signing a consent form, volunteers provided a blood sample (20 ml) to establish cell cultures at 52 h. For CA analysis, 100 complete metaphase cells from each subject were evaluated. The CA frequency was significantly higher in smokers (8.38 +/- 0.61) than in non-smokers (3.13 +/- 0.29), showing the highest number of CA (14.83 +/- 1.01) among heavy smokers (>20 pack-years). Interestingly, light smokers (< or =10 pack-years) also showed a significant increase in CA when compared to non-smokers (6.62 +/- 0.53 versus 3.13 +/- 0.29, P < 0.01, respectively). In addition, a significant positive correlation was found between the frequency of CA and the intensity of smoking in pack-years (R2 = 0.60). Our study indicates that the genotoxic effects in lymphocytes from smokers are most likely caused by cigarette smoke constituents, providing scientific evidence to encourage national campaigns to prevent tobacco consumption.

[Genotoxicity from exposure to cigarettes in young smokers in Colombia]. / Genotoxicidad por exposición a cigarrillos en fumadores jóvenes en Colombia

OBJECTIVE: To evaluate the frequency of chromosome aberrations (CAs) in the peripheral blood lymphocytes of young cigarette smokers in the city of Popayán, Colombia. METHODS: In this cytogenetic case-control study there were 32 young cigarette smokers and 32 nonsmokers. All of them were between 19 and 29 years old and none used psychoactive drugs, suffered from chronic or infectious diseases, or had been exposed to chemotherapy or radiation therapy or to chemical agents in their work. A survey was used to obtain demographic information, occupational information (type of employment, type of and length of exposure to chemical agents), lifestyle information (consumption of alcoholic beverages and psychoactive drugs), and information on smoking (current or former smoker, number of cigarettes smoked daily, length of time smoking, and type of cigarettes smoked). The cases were matched with the controls by age (+/- 5 years) and sex. The microscopic study of the CAs using lymphocyte cultures was carried out under the light microscope with 100X magnification. For each study participant, 100 complete metaphase cells (2n = 46 chromosomes) were analyzed, counting the structural CAs (chromatid breaks and chromosome breaks) and numerical CAs (change in the number of chromosomes). The frequency of CAs was adjusted for alcohol consumption, using a univariate linear model. RESULTS: The frequency of total CAs was significantly greater in the young cigarettes smokers (6.02 +/- 0.52) than in the nonsmokers (3.04 +/- 0.50), and the greatest number of CAs (7.77 +/- 0.88) was found in those who had a pack-year value of more than 3.0. In addition, there was a dose-effect relationship, shown by the increase in the frequency of CAs with an increase in the pack-years of consumption (coefficient of determination = 0.2257). CONCLUSION: We confirmed the association between cigarette consumption and CAs in young people who smoked relatively little. These results should be taken into account in order to formulate national smoking prevention policies and to evaluate their outcomes, from both the social, economic, and environmental standpoint and the standpoint of the health of future generations.

Genotoxicidad por exposición a cigarrillos en fumadores jóvenes en Colombia / Genotoxicity from exposure to cigarettes in young smokers in Colombia

OBJETIVO: Evaluar la frecuencia de aberraciones cromosómicas (AC) en los linfocitos de sangre periférica de jóvenes fumadores de cigarrillos de la ciudad de Popayán, Colombia. MÉTODOS: En este estudio citogenético de casos y testigos participaron 32 jóvenes fumadores de cigarrillos y 32 jóvenes no fumadores. Todos se encontraban entre los 19 y 29 años de edad y ninguno consumía drogas psicoactivas, padecía de enfermedades crónicas o infecciosas o había estado expuesto a quimioterapia, radioterapia o a agentes químicos en el ámbito ocupacional. Se aplicó una encuesta a fin de obtener información demográfica, ocupacional (tipo de empleo, tipo y tiempo de exposición a agentes químicos), estilo de vida (consumo de bebidas alcohólicas y de drogas psicoactivas) y hábitos tabáquicos (fumador actual o previo, número de cigarrillos que fumaba diariamente, tiempo que llevaba fumando y tipo de cigarrillos que fumaba). Se parearon los casos con los testigos según la edad (± 5 años) y el sexo. El estudio microscópico de las AC a partir de cultivos de linfocitos se realizó bajo el microscopio óptico con un aumento de 100X. Se analizaron 100 células en metafase completa (2n= 46 cromosomas) por persona y se contaron las AC estructurales (quiebres cromatídicos y cromosómicos) y numéricas (cambio en el número de cromosomas). Se ajustó la frecuencia de AC en función del consumo de alcohol mediante un modelo lineal unifactorial. RESULTADOS: La frecuencia de AC totales fue significativamente mayor en los jóvenes fumadores de cigarrillos (6,02 ± 0,52) que en los que no fumaban (3,04 ± 0,50) y el mayor número de AC (7,77 ± 0,88) se encontró en los que fumaban más de 3,0 años-cajetilla. Además, se observó una relación entre dosis y efecto, demostrada por el aumento de la frecuencia de AC al aumentar la intensidad del consumo (r² = 0,2257). CONCLUSION: Se confirmó la presencia de una asociación entre el consumo de cigarrillos y las AC en jóvenes que fumaban poco. Estos resultados se deben tomar en cuenta para formular las políticas nacionales de prevención del tabaquismo y para evaluar las consecuencias del hábito de fumar, tanto desde el punto de vista social, económico y ambiental, como desde el punto de vista de la salud de las generaciones futuras.