Dados do Trabalho

Título

GERMLINE MUTATIONS IN PANCREATIC CARCINOMA PATIENTS WITH MISCEGENATED ETHNIC BACKGROUND

Introdução

Hereditary factors in pancreatic cancer was mainly investigated in caucasian people. In Brazil, around 47% of the population are self-reported “pardos”, according to IBGE–PNAD, with miscegenated European, African and Indigenous ethnic backgrounds.

Objetivo

Our aim was to evaluate the spectrum and frequency of germline variants in cancer predisposing genes in pancreatic cancer patients, self-reported “pardos”, due to scarce data.

Método

Patients with histopathological diagnosis of non-endocrine pancreatic carcinoma were included, regardless of family history and clinical stage and answered a questionnaire of family history and habits. Genomic DNA was obtained from peripheral blood for Next Generation Sequencing, using the Illumina TruSight Hereditary Cancer panel, comprising 113 cancer predisposing genes. Reported variants are exonic or cannonical splicing, coverage ≥30x and variant allele frequency (VAF) ≥0.4.

Resultado

In the 2018-2021 period, 48 patients were evaluated, with mean age 60 years (34-86), among whom, 23% with young age (≤50 years) and 27 women (56%). Twenty-four (50%) reported cases of any cancer in first-degree relatives. Regarding risk factors, 25 patients (52%) reported smoking and 15 (31%) were previously obese. Twenty-one (44%) were diagnosed with T4 or metastatic disease. Six (12,5%) patients presented pathogenic/likely pathogenic variants in the following genes: BRCA1, BRCA2 (new frameshift), CHEK2, FH, MRE11 and RAD51C. Only two mutation carriers reported positive family history.

Conclusão

In this group of miscegenated patients with pancreatic carcinoma, half of the patients reported positive family history of cancer in first degree relatives and a considerable fraction 13% were carriers of pathogenic germline variants in cancer predisposing genes, mainly genes related to homologous recombination DNA repair. Future analyzes in a larger number of patients will allow a better understanding of the hereditary mutational profile of pancreatic carcinoma, especially in non-Caucasian populations.

Palavras-chave

pancreatic carcinoma; germline; pardos.