Correction: Earl et al. Somatic Mutation Profiling in the Liquid Biopsy and Clinical Analysis of Hereditary and Familial Pancreatic Cancer Cases Reveals KRAS Negativity and a Longer Overall Survival. Cancers 2021, 13, 1612

The authors wish to make the following corrections to this paper [...]

Susceptibility loci for pancreatic cancer in the Brazilian population

Background Pancreatic adenocarcinoma (PA) is a very aggressive cancer and has one of the poorest prognoses. Usually, the diagnosis is late and resistant to conventional treatment. Environmental and genetic factors contribute to the etiology, such as tobacco and alcohol consumption, chronic pancreatitis, diabetes and obesity. Somatic mutation in pancreatic cancer cells are known and SNP profile by GWAS could access novel genetic risk factors for this disease in different population context. Here we describe a SNP panel for Brazilian pancreatic cancer, together with clinical and epidemiological data. Methods 78 pancreatic adenocarcinoma and 256 non-pancreatic cancer subjects had 25 SNPs genotyped by real-time PCR. Unconditional logistic regression methods were used to assess the main effects on PA risk, using allelic, co-dominant and dominant inheritance models. Results 9 SNPs were nominally associated with pancreatic adenocarcinoma risk, with 5 of the minor alleles conferring protective effect while 4 related as risk factor. In epidemiological and clinical data, tobacco smoking, diabetes and pancreatitis history were significantly related to pancreatic adenocarcinoma risk. Polygenic risk scores computed using the SNPs in the study showed strong associations with PA risk. Conclusion We could assess for the first time some SNPs related with PA in Brazilian populations, a result that could be used for genetic screening in risk population such as familial pancreatic cancer, smokers, alcohol users and diabetes patients.

Long-term yield of pancreatic cancer surveillance in high-risk individuals

ObjectiveWe aimed to determine the long-term yield of pancreatic cancer surveillance in hereditary predisposed high-risk individuals.DesignFrom 2006 to 2019, we prospectively enrolled asymptomatic individuals with an estimated 10% or greater lifetime risk of pancreatic ductal adenocarcinoma (PDAC) after obligatory evaluation by a clinical geneticist and genetic testing, and subjected them to annual surveillance with both endoscopic ultrasonography (EUS) and MRI/cholangiopancreatography (MRI/MRCP) at each visit.Results366 individuals (201 mutation-negative familial pancreatic cancer (FPC) kindreds and 165 PDAC susceptibility gene mutation carriers; mean age 54 years, SD 9.9) were followed for 63 months on average (SD 43.2). Ten individuals developed PDAC, of which four presented with a symptomatic interval carcinoma and six underwent resection. The cumulative PDAC incidence was 9.3% in the mutation carriers and 0% in the FPC kindreds (p<0.001). Median PDAC survival was 18 months (range 1–32). Surgery was performed in 17 individuals (4.6%), whose pathology revealed 6 PDACs (3 T1N0M0), 7 low-grade precursor lesions, 2 neuroendocrine tumours <2 cm, 1 autoimmune pancreatitis and in 1 individual no abnormality. There was no surgery-related mortality. EUS detected more solid lesions than MRI/MRCP (100% vs 22%, p<0.001), but less cystic lesions (42% vs 83%, p<0.001).ConclusionThe diagnostic yield of PDAC was substantial in established high-risk mutation carriers, but non-existent in the mutation-negative proven FPC kindreds. Nevertheless, timely identification of resectable lesions proved challenging despite the concurrent use of two imaging modalities, with EUS outperforming MRI/MRCP. Overall, surveillance by imaging yields suboptimal results with a clear need for more sensitive diagnostic markers, including biomarkers.

Somatic Mutation Profiling in the Liquid Biopsy and Clinical Analysis of Hereditary and Familial Pancreatic Cancer Cases Reveals KRAS Negativity and a Longer Overall Survival

Pancreatic ductal adenocarcinoma (PDAC) presents many challenges in the clinic and there are many areas for improvement in diagnostics and patient management. The five-year survival rate is around 7.2% as the majority of patients present with advanced disease at diagnosis that is treatment resistant. Approximately 10–15% of PDAC cases have a hereditary basis or Familial Pancreatic Cancer (FPC). Here we demonstrate the use of circulating free DNA (cfDNA) in plasma as a prognostic biomarker in PDAC. The levels of cfDNA correlated with disease status, disease stage, and overall survival. Furthermore, we show for the first time via BEAMing that the majority of hereditary or familial PDAC cases (around 84%) are negative for a KRAS somatic mutation. In addition, KRAS mutation negative cases harbor somatic mutations in potentially druggable genes such as KIT, PDGFR, MET, BRAF, and PIK3CA that could be exploited in the clinic. Finally, familial or hereditary cases have a longer overall survival compared to sporadic cases (10.2 vs. 21.7 months, respectively). Currently, all patients are treated the same in the clinic with cytotoxic agents, although here we demonstrate that there are different subtypes of tumors at the genetic level that could pave the way to personalized treatment.