Heritable genomic diversity in breast cancer driver genes and associations with risk in a Chilean population

BACKGROUND: Driver mutations are the genetic components responsible for tumor initiation and progression. These variants, which may be inherited, influence cancer risk and therefore underlie many familial cancers. The present study examines the potential association between SNPs in driver genes SF3B1 (rs4685), TBX3 (rs12366395, rs8853, and rs1061651) and MAP3K1 (rs72758040) and BC in BRCA1/2-negative Chilean families. METHODS: The SNPs were genotyped in 486 BC cases and 1258 controls by TaqMan Assay. RESULTS: Our data do not support an association between rs4685:C > T, rs8853:T > C, or rs1061651:T > C and BC risk. However, the rs12366395-G allele (A/G + G/G) was associated with risk in families with a strong history of BC (OR = 1.2 [95% CI 1.0-1.6] p = 0.02 and OR = 1.5 [95% CI 1.0-2.2] p = 0.02, respectively). Moreover, rs72758040-C was associated with increased risk in cases with a moderate-to-strong family history of BC (OR = 1.3 [95% CI 1.0-1.7] p = 0.02 and OR = 1.3 [95% CI 1.0-1.8] p = 0.03 respectively). Finally, risk was significantly higher in homozygous C/C cases from families with a moderate-to-strong BC history (OR = 1.8 [95% CI 1.0-3.1] p = 0.03 and OR = 1.9 [95% CI 1.1-3.4] p = 0.01, respectively). We also evaluated the combined impact of rs12366395-G and rs72758040-C. Familial BC risk increased in a dose-dependent manner with risk allele count, reflecting an additive effect (p-trend = 0.0002). CONCLUSIONS: Our study suggests that germline variants in driver genes TBX3 (rs12366395) and MAP3K1 (rs72758040) may influence BC risk in BRCA1/2-negative Chilean families. Moreover, the presence of rs12366395-G and rs72758040-C could increase BC risk in a Chilean population.

Cáncer sincrónico y metacrónico detectado con PET/CT en población oncológica / Multiple primary malignant neoplasms detected by PET/CT in cancer patients

Background Imaging with F18-fluorodeoxyglucose PET/CT is used to determine sites of abnormal glucose metabolism and can be used to characterize and localize many types of tumors. Aim To assess the prevalence of multiple primary malignant neoplasms (MPMN) detected by PET/CT in cancer patients. Material and Methods F18-fluorodeoxyglucose PET/CT scans performed to 800 patients with a newly diagnosed cancer or with already treated tumors were retrospectively reviewed. In patients whose examination described incidental findings not related to the primary tumor, a research was done about further laboratory, imaging or pathological studies. Results In 188 PET/CT scans (23%) an incidental finding was found. Of these, 66 (35%) were considered as MPMN, 12 as atypical metastases of a known primary tumor, 14 as false positive images (inflammatory or physiologic uptake) and 29 as benign or low grade tumors. In 67 cases (36% of all incidental tumors), the finding was not confirmed. Seven percent of patients with a newly diagnosed tumor had a synchronic MPMN detected by PET/CT. Nine percent of patients with treated tumors developed a metachronous MPMN during their follow up. The most common incidental tumors were thyroid cancer in 15 cases, kidney cancer in 13, lung cancer in 10, colorectal carcinoma in 9, breast cancer in 6, prostate cancer in 4, non-Hodgkin lymphoma in 3 and pancreatic cancer in 2. Conclusions A MPMN is detected by PET/CT in a significant number of cancer patients.

Manejo paliativo del cáncer de vesícula biliar irresecable o metastásico: Conclusiones del Consenso Latinoamericano de Manejo del Cáncer de Vesícula Biliar / Palliative treatment for locally advanced or metastatic gallbladder cancer: conclusions of the Latin American Consensus meeting for the management of gallbladder cancer

Gallbladder cancer is a rare disease in Western developed countries, but it is a highly prevalent and lethal disease in Chile and other countries in Latin America. No randomized controlled trials have been performed in gallbladder cancer to establish standard treatments. We therefore performed the first Latin American consensus meeting for the management of gallbladder cancer. In this article we present the conclusions of the panel of experts for the palliative treatment of unresectable or metastatic gallbladder cancer based on a review of the literature, the discussion of the participating experts and the opinion of the assistants. The topics reviewed included: 1.- Gallbladder Cancer and Cholangiocarcinoma -are they the same disease?; 2. - Palliative Chemotherapy: Indications, Drugs and Schedules; 3. - Palliative Radiotherapy; 4.- Palliative Surgery; 5.-Management of Malignant Biliary Obstruction.

Molecular analysis of the eighteen most frequent mutations in the BRCA1 gene in 63 Chilean breast cancer families

BRCA1 gene mutations account for nearly all families with multiple cases of both early onset breast and/or ovarian cancer and about 30% of hereditary breast cancer. Although to date more than 1,237 distinct mutations, polymorphisms, and variants have been described, several mutations have been found to be recurrent in this gene. We have analyzed 63 Chilean breast/ovarian cancer families for eighteen frequent BRCA1 mutations. The analysis of the five exons and two introns in which these mutations are located was made using mismatch PCR assay, ASO hybridization assay, restriction fragment analysis, allele specific PCR assay and direct sequentiation techniques. Two BRCA1 mutations (185delAG and C61G) and one variant of unknown significance (E1250K) were found in four of these families. Also, a new mutation (4185delCAAG) and one previously described polymorphism (E1038G) were found in two other families. The 185delAG was found in a 3.17 % of the families and the others were present only in one of the families of this cohort. Therefore these mutations are not prominent in the Chilean population. The variant of unknown significance and the polymorphism detected could represent a founder effect of Spanish origin.

Transfusión de granulocitos en pacientes neutropénicos febriles / Granulocyte transfusion in febrile neutropenic patients

Desde 1996 a la fecha hemos transfundido con granulocitos a 20 pacientes con 21 episodios de neutropenia febril con criterios de extrema gravedad. 14 episodios correspondieron a sepsis con germen conocido y 7 neutropenia febril sin germen aislado. Los pacientes recibieron un promedio de 3.7 aféresis, con 2.17(potencia 10) granulocitos por cada una. Los donantes fueron seleccionados entre familiares directos con estudios rutinarios para la donaci¢n de sangre, los que fueron condicionados con factor estimulante de colonias granulocíticas previa al procedimiento aferético. 15 pacientes sobrevivieron al episodio neutropénico con resolución de cuadro infeccioso. Las reacciones adversas transfucionales en los receptores fueron leves y no hubo complicaciones clínicas en los donantes. Las transfusiones de granulocitos parecen ser efectivas en pacientes con neutropenia febril sin respuesta a antibióticos