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Balboa E.,Grupo Medicina Xenomica CIBERER | Duran G.,Complejo Hospitalario de Santiago de Compostela CHUS | Lamas M.J.,Complejo Hospitalario de Santiago de Compostela CHUS | Gomez-Caamano A.,Complejo Hospitalario de Santiago de Compostela CHUS | And 5 more authors.
Pharmacogenomics | Year: 2010

Aims: The identification of predictive markers of response to chemoradiotherapy treatment remains a promising approach for patient management in order to obtain the best response with minor side effects. Initially, we investigated whether the analysis of several markers previously studied and others not yet evaluated could predict response to 5-fluorouracil-and capecitabine-based neoadjuvant treatment in locally advanced rectal cancer. Methods & materials: We studied germline and tumoral samples of 65 stage II/III rectal patients. A panel of pharmacogenetic markers was genotyped in paired peripheral blood samples and rectal cancer tumors. Results: Our results seem to confirm the previously described association of thymidylate synthase and the prediction of chemoradiotherapy response in rectal cancer. However, it failed to confirm the clinical utility proposed for XRCC1, ERCC1, ERCC2, MTHFR and EGFR polymorphisms in blood/germline samples. Subsequently, with the aim of improving prediction of individual response and assessing the role of studied polymorphisms in response to treatment, we determined if changes in tumor response to these markers could predict clinical outcome. We found a high degree of changes between germline and tumor samples, mainly somatic mutations without microsatellite instability, and a minor frequency of loss-of-heterozygosity events. In tumoral samples, XRCC1 appeared to be significantly associated (p = 0.006) with downstaging of the tumor (odds ratio: 7.93; 95% CI: 1.03-60.83), but the increasing of TYMS low-expression alleles contradict the previous results observed in germline samples. Conclusion: The detection of somatic mutations in rectal cancer tumors led us to re-evaluate the utility of the tests performed in blood samples for these polymorphisms in rectal cancer. Furthermore, studies aimed at assessing the influence of pharmacogenetic markers in treatment response performed in blood samples should take into account the particular pattern of hypermutability present in each tumor type. We hypothesize that different patterns of hypermutability present in each tumor type would be related to the different results in association studies related to response to the treatment. © 2010 Future Medicine Ltd. Source


Crujeiras A.B.,Institute Investigacion Sanitaria IDIS | Crujeiras A.B.,CIBER ISCIII | Cueva J.,Complejo Hospitalario de Santiago de Compostela CHUS | Vieito M.,Complejo Hospitalario de Santiago de Compostela CHUS | And 6 more authors.
Journal of Endocrinological Investigation | Year: 2012

Objective: To evaluate for the first time in Spain if the association between obesity and breast cancer prognosis is similar to that reported in other countries with non Mediterranean dietary patterns. Methods: Weight and height and other variables of interest, tumor characteristics and current clinical status 3 yr after diagnosis were retrieved from medical files of breast cancer women diagnosed during 2006. A total of 159 cases with complete information were studied and categorized according to the World Health Organization criteria in normal-/under-weight, overweight, and obese. Results: Among breast cancer patients, 70.4% were classified as overweight/ obese and 29.6% as normal weight. Prevalence of obesity was high (38.4%) in comparison with information reported for healthy women of the same region (27.11%) and was higher among post-menopausal patients and in women with low level of alcohol and tobacco consumption. Moreover, overweight/ obese cases (79.5%) tended to have more often human epidermal growth factor receptor 2 status negative when compared with those with normal weight (70.2%; p=0.097) and the survival curves tended to be influenced by body mass index although without statistical significance. Conclusions: Overweight/obesity in a Mediterranean country is highly prevalent among breast cancer patients. Our results support a putative influence of obesity per se and not the alimentary patterns as a prognostic factor in breast cancer patients justifying the need to perform larger prospective studies. ©2012, Editrice Kurtis. Source

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