Gustavo Hernández

Clinical manifestations of colorectal cancer patients from a large multicenter study in Colombia

AbstractColorectal cancer (CRC) is a major public health problem, and its incidence is rising in developing countries. However, studies characterizing CRC clinicopathological features in cases from developing countries are still lacking. The goal of this study was to evaluate clinicopathological and demographic features in one of the largest CRC studies in Latin America.The study involved over 1525 CRC cases recruited in a multicenter study in Colombia between 2005 and 2014 as part of ongoing genetic and epidemiological studies. We gathered clinicopathological data such as age at diagnosis, sex, body mass index, tobacco and alcohol consumption, family history of cancer, and tumor features including location, histological type, and stage. Statistical analyses were performed to test the association between age of onset, sex, and clinical manifestations.The average age at CRC diagnosis was 57.4 years, with 26.5% of cases having early-onset CRC (diagnosed by age 50 years). Most cases were women (53.2%; P = 0.009), 49.2% were overweight or obese, 49.1% were regular alcohol drinkers, 52% were smokers/former smokers, and 12.2% reported relatives with cancer. Most tumors in the study were located in the rectum (42.7%), were adenocarcinomas (91.5%), and had advanced stage (T3–T4, 79.8%). Comparisons by sex found that male cases were more likely to be obese (36.5% vs 31.1%; P = 0.001), less likely to have a family history of cancer (9.7% vs 15.3%; P = 0.016), and more likely to have advanced-stage tumors (83.9% vs 76.1%; P = 0.036). Comparisons by age of onset found that early-onset cases were more likely to be women (59.3% vs 51.0%; P = 0.005) and report a family history of cancer (17.4% vs 10.2%; P = 0.001).To our knowledge, our study is the largest report of clinicopathological characterization of Hispanic CRC cases, and we suggest that further studies are needed to understand CRC etiology in diverse Hispanic populations.

Telomerase activity in cervical scrapes of women with high‑grade cervical disease: A nested case-control study

Epidemiological information on telomerase activity (TA) and development of cervical lesions is scarce. A nested case-control study was carried out within a cohort of Colombian women tested for Human Papillomavirus (HPV). Measurement of TA was done in cervical scrapes of 25 women who developed High Grade Squamous Intraepithelial Lesion (HGSIL) during the first 6 years of follow-up and was compared with that of 104 control women who maintained normal cytology during the entire follow-up. TA was measured by a telomerase repeat amplification protocol-ELISA. TA and HPV infections were significantly more frequent in cases than in controls. Likewise, 68% of the cases were positive for both TA and HPV compared with only 7.7% of the controls (P<0.0001). Factors independently associated with increased odds of HGSIL included TA, high risk HPV (hrHPV) infections and multiple parities. When restricted to hrHPV positive women, TA was strongly associated with increased odds of HGSIL (adjusted odds ratio=37.94, 95% confidence interval, 1.64–678.1). In addition to an infection with hrHPV, TA appears to be a significant cofactor for HGSIL.

Abstract C22: Telomerase activity and HR‐HPV infection frequently are present before detection of high grade cervical lesions

Telomerase activation have been considered as a fundamental step in the immortalization process because majority nonmalignant somatic tissue shows undetectable or no telomerase activity. A few numbers of studies in cervical cancer have showed an increase in the telomerase activity with grade of lesion, and Human Papillomavirus (HPV) infection has been associated in some studies with telomerase activation. However until now there are not follow up studies that measure the telomerase activity along the time. We describe here results about telomerase activity and HPV infection during 7 years of follow up in women that belong to the Bogota cohort. Samples were obtained every six months during follow up and we had in average four samples by woman. Telomerase activity was analyzed in 58 samples of 17 women that during follow up developed High Grade Squamous Intraepithelial Lesions (HGSIL) and 149 samples of 34 women that during follow up had normal cytology using a TeloTAGGG Telomerase PCR ELISA kit (Roche Applied Science). The HPV infection was previously tested using a GP5+/GP6+mediated PCR‐EIA and typing using a Reverse Line Blot assay (RLB). Of the 17 women that developed HGSIL along follow up; 12 (70.5%) had HPV infection and telomerase activity at the same time of HGSIL diagnosis or in a previous visit, these women had infections with high risk types (HR) principally with those belong to the alpha 9 specie, 2 (17.7%) showed only transitory events of HPV infection and 2 (11.8%) had normal cytology without HPV infection or telomerase activity. Average time to develop HGSIL was 13.5 months. In normal women we observed diverse results. Of the 34 women; 21 (61.8%) had HPV transitory infections with high risk and/or low risk types sometime during follow up and only 12 (35.2%) of them were positive for telomerase activity sometime in follow up independently of HPV infection. Interestingly, 8 (23.5%) women had HPV‐HR infection during follow up and they were never positive for telomerase activity and 5 (14.7%) women didn9t have HPV infection and telomerase activity. Detection of HR‐HPV infection and telomerase activity at the same time likes to predict the risk of HGSIL. Our results support the idea that telomerase activity and HR‐HPV infection can be used as progression markers for the development of HGSIL. Citation Information: Cancer Res 2009;69(23 Suppl):C22.