Lilian Jara is a Geneticist with a PhD in Biomedical Sciences and the Head of the Human Genetic Program at University of Chile. She is an expert in cancer genetics, with a research focus on familial breast cancer. She has focused her research in search for new genetic factors involved in the development of familial breast cancer in patients without point mutation in BRCA1/2 genes. She has published several articles with novel findings on Chilean familial breast cancer.
Breast Cancer (BC) is one of the most frequent cancers affecting women worldwide. In Chile, BC has the highest mortality rate among cancers (15.69/100,000 women). Recent evidence supports a role for microRNAs (miRNAs) in BC development and progression. Single-Nucleotide Polymorphisms (SNPs) are the most common type of variation in the human genome. SNPs in miRNA genes can alter expression, maturation or target binding affinity, thus contributing to the development of cancer. Studies have documented that SNPs in miRNA(s) targeting BRCA1/2 genes alter BRCA gene expression levels. MiR-1245a targets the BRCA2 gene. Sequencing pre-miR-1245a in 107 BRCA1/2-negative BC probands from high-risk families resulted in the identification of rs60611793, which corresponds to a 1-bp deletion. This variant was detected in an early-onset (Diagnosis at 30 years of age), Triple-Negative (TN) BC case without a family history of BC. Given the clinic-pathological features of the patient carrying the deletion, we used Sanger sequencing to screen for rs60611793 in another 181 early-onset and TN BC cases and 192 healthy individuals. The deletion was detected in another four BC cases and 3 of 192 controls. The five cases with the deletion had early-onset BC. However, there was no correlation between rs60611793 and histological BC type. Two of the five cases were poorly-differentiated ductal carcinomas, one was a medullary carcinoma, one was an in-situ carcinoma and the histopathological report for the fifth case was unavailable. Therefore, this deletion could be related to the development of early-onset BC and high-grade malignant neoplasms, with no predominant ER/PR/Her2/Neu status.
Sebastian Morales Pison is a Biotechnology Engineer, completed his Masters in Biotechnology and currently pursuing his PhD in Biomedical Sciences at the University of Chile. He has expertise in cancer genetics, with a research focus on genetic variants in microRNA genes associated with familial breast cancer. He has published original scientific articles with novel findings on Chilean familial breast cancer patients.
Breast Cancer (BC) is one of the most frequent tumors affecting women worldwide. Single-Nucleotide Polymorphisms (SNPs) in microRNAs (miRNAs) likely contribute to BC susceptibility. Using Sanger sequencing, we detected rs4541843: C>T (pre-miR-182 boundaries) in 99 BRCA1/2-negative BC patients from high-risk families. While mir-182 is known to be involved in breast carcinogenesis, there are no association studies in the literature regarding the contribution of rs4541843 to BC susceptibility. Therefore, we evaluated the association of the SNP rs4541843: C>T with BC risk in non-carriers of BRCA1/2 mutations from a South American population. The SNP was genotyped in 440 BRCA1/2-negative Chilean BC cases and 1048 controls. The frequency of rs4541843-T was higher in cases than controls (0.46 vs. 0.31, p=0.01). Furthermore, homozygous T/T- and T-allele carriers (C/T + T/T) had a significantly increased BC risk (OR=1.5 [95% CI 1.0-2.2] p=0.03 and OR=1.2 [95% CI 1.0-1-5] p=0.01, respectively), indicating that the T allele is positively associated with BC susceptibility. This the first association study on rs454183 and BC risk. In our previous work, we showed that TOX3-rs3803662: C>T was significantly associated with familial BC risk. Given that TOX3 is a target of miR-182 and that both the TOX3 rs3803662-T and pri-miR-182 rs454183-T alleles are associated with elevated BC risk, we evaluated their combined effect. Risk of familial BC increased in a dose-dependent manner with the number of risk alleles (p-trend=0.0005), indicating an additive effect.