Lack of association of CD44-rs353630 and CHI3L2-rs684559 with pancreatic ductal adenocarcinoma survival.

Published on Apr 7, 2021in Scientific Reports3.998
· DOI :10.1038/S41598-021-87130-0
Manuel Gentiluomo6
Estimated H-index: 6
(UniPi: University of Pisa),
C. Corradi1
Estimated H-index: 1
(UniPi: University of Pisa)
+ 28 AuthorsGabriele Capurso56
Estimated H-index: 56
(UniSR: Vita-Salute San Raffaele University)
Although pancreatic ductal adenocarcinoma (PDAC) survival is poor, there are differences in patients' response to the treatments. Detection of predictive biomarkers explaining these differences is of the utmost importance. In a recent study two genetic markers (CD44-rs353630 and CHI3L2-rs684559) were reported to be associated with survival after PDAC resection. We attempted to replicate the associations in 1856 PDAC patients (685 resected with stage I/II) from the PANcreatic Disease ReseArch (PANDoRA) consortium. We also analysed the combined effect of the two genotypes in order to compare our results with what was previously reported. Additional stratified analyses considering TNM stage of the disease and whether the patients received surgery were also performed. We observed no statistically significant associations, except for the heterozygous carriers of CD44-rs353630, who were associated with worse OS (HR = 5.01; 95% CI 1.58-15.88; p = 0.006) among patients with stage I disease. This association is in the opposite direction of those reported previously, suggesting that data obtained in such small subgroups are hardly replicable and should be considered cautiously. The two polymorphisms combined did not show any statistically significant association. Our results suggest that the effect of CD44-rs353630 and CHI3L2-rs684559 cannot be generalized to all PDAC patients.
#1C. Corradi (UniPi: University of Pisa)H-Index: 1
#2Manuel Gentiluomo (UniPi: University of Pisa)H-Index: 6
Last. Daniele Campa (UniPi: University of Pisa)H-Index: 34
view all 54 authors...
Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second cancer-related cause of death by 2030. Identifying novel risk factors, including genetic risk loci, could be instrumental in risk stratification and implementation of prevention strategies. Long noncoding RNAs (lncRNAs) are involved in regulation of key biological processes, and the possible role of their genetic variability has been unexplored so far. Combining genome wide association studies and functional data, we inves...
1 CitationsSource
#1Manuel Gentiluomo (UniPi: University of Pisa)H-Index: 6
#2Federico Canzian (DKFZ: German Cancer Research Center)H-Index: 82
Last. Daniele Campa (UniPi: University of Pisa)H-Index: 34
view all 6 authors...
Pancreatic cancer (PC), particularly its most common form, pancreatic ductal adenocarcinoma (PDAC), is relatively rare but highly lethal. Knowledge about PC risk factors could in the long term contribute to early diagnosis and mortality reduction. We review the current status of research on germline genetic factors for PC risk. Genome-wide association studies (GWAS) successfully identified common loci convincingly associated with PC risk, an endeavor that is still ongoing. The function of only a...
2 CitationsSource
#2Manuel Gentiluomo (UniPi: University of Pisa)H-Index: 6
Last. Daniele Campa (UniPi: University of Pisa)H-Index: 34
view all 66 authors...
Background Most cases of pancreatic ductal adenocarcinoma (PDAC) are asymptomatic in early stages, and the disease is typically diagnosed in advanced phases, resulting in very high mortality. Tools to identify individuals at high risk of developing PDAC would be useful to improve chances of early detection. Objective We generated a polygenic risk score (PRS) for PDAC risk prediction, combining the effect of known risk SNPs, and carried out an exploratory analysis of a multifactorial score. Metho...
5 CitationsSource
#1Daniele Campa (UniPi: University of Pisa)H-Index: 34
#2Manuel Gentiluomo (UniPi: University of Pisa)H-Index: 6
Last. Federico Canzian (DKFZ: German Cancer Research Center)H-Index: 82
view all 59 authors...
Early onset pancreatic cancer (EOPC) is a rare disease with a very high mortality rate. Almost nothing is known on the genetic susceptibility of EOPC, therefore we performed a genome-wide association study (GWAS) to identify novel genetic variants specific for patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) at younger ages. In the first phase, conducted on 821 cases with age of onset
2 CitationsSource
#1Rebecca L. Siegel (ACS: American Cancer Society)H-Index: 67
#2Kimberly D. Miller (ACS: American Cancer Society)H-Index: 28
Last. Ahmedin Jemal (ACS: American Cancer Society)H-Index: 139
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Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data on population-based cancer occurrence. Incidence data (through 2016) were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2017) were collected by the National Center for Health Statis...
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#1Ofure Obazee (DKFZ: German Cancer Research Center)H-Index: 9
#2Livia ArchibugiH-Index: 13
Last. Federico Canzian (DKFZ: German Cancer Research Center)H-Index: 82
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: Rare truncating BRCA2 K3326X (rs11571833) and pathogenic CHEK2 I157T (rs17879961) variants have previously been implicated in familial pancreatic ductal adenocarcinoma (PDAC), but not in sporadic cases. The effect of both mutations in important DNA repair genes on sporadic PDAC risk may shed light on the genetic architecture of this disease. Both mutations were genotyped in germline DNA from 2,935 sporadic PDAC cases and 5,626 control subjects within the PANcreatic Disease ReseArch (PANDoRA) c...
11 CitationsSource
#1Manuel Gentiluomo (DKFZ: German Cancer Research Center)H-Index: 6
#2Paula Puchalt García (Polytechnic University of Valencia)H-Index: 1
Last. Daniele Campa (UniPi: University of Pisa)H-Index: 34
view all 24 authors...
: Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis, caused by various factors, such as the aggressiveness of the disease, the limited therapeutic options and the lack of early detection and risk markers. The ATP binding cassette subfamily C member 2 (ABCC2) protein plays a critical role in response to various drugs and is differentially expressed in gemcitabine sensitive and resistant cells. Moreover, single nucleotide polymorphisms (SNPs) in the gene have been associated ...
4 CitationsSource
#1Christos Dimitrakopoulos (Swiss Institute of Bioinformatics)H-Index: 8
#2Bart Vrugt (UZH: University of Zurich)H-Index: 16
Last. Lukasz Filip Grochola (UZH: University of Zurich)H-Index: 3
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Importance Surgery currently offers the only chance for a cure in pancreatic ductal adenocarcinoma (PDAC), but it carries a significant morbidity and mortality risk and results in varying oncologic outcomes. At present, to our knowledge, there are no tests available before surgical resection to identify tumors with an aggressive biological phenotype that could guide personalized treatment strategies. Objective Identification of noninvasive genetic biomarkers that could direct therapy in patients...
12 CitationsSource
#1Maria Escala-Garcia (NKI-AVL: Netherlands Cancer Institute)H-Index: 3
#2Qi Guo (University of Cambridge)H-Index: 10
Last. Marjanka K. Schmidt (NKI-AVL: Netherlands Cancer Institute)H-Index: 67
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Background: We examined the associations between germline variants and breast cancer mortality using a large meta-analysis of women of European ancestry. Methods: Meta-analyses included summary estimates based on Cox models of twelve datasets using ~10.4 million variants for 96,661 women with breast cancer and 7697 events (breast cancer-specific deaths). Oestrogen receptor (ER)-specific analyses were based on 64,171 ER-positive (4116) and 16,172 ER-negative (2125) patients. We evaluated the prob...
16 CitationsSource
#1Weiqiang Li (ISMMS: Icahn School of Medicine at Mount Sinai)H-Index: 1
#2Mridu Middha (ISMMS: Icahn School of Medicine at Mount Sinai)H-Index: 4
Last. Robert J. Klein (ISMMS: Icahn School of Medicine at Mount Sinai)H-Index: 37
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Background: Most men diagnosed with prostate cancer have low-risk cancers. How to predict prostate cancer progression at the time of diagnosis remains challenging.Objective: To identify single nucl ...
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