@article{3029921,
    title = "Associations between pancreatic expression quantitative traits and risk
of pancreatic ductal adenocarcinoma",
    author = "Pistoni, Laura and Gentiluomo, Manuel and Lu, Ye and de Maturana, and Evangelina Lopez and Hlavac, Viktor and Vanella, Giuseppe and Darvasi, and Erika and Milanetto, Anna Caterina and Oliverius, Martin and Vashist, and Yogesh and Di Leo, Milena and Mohelnikova-Duchonova, Beatrice and and Talar-Wojnarowska, Renata and Gheorghe, Cristian and Petrone, Maria and Chiara and Strobel, Oliver and Arcidiacono, Paolo Giorgio and Vodickova, and Ludmila and Szentesi, Andrea and Capurso, Gabriele and Gajdan, Laszlo and and Malleo, Giuseppe and Theodoropoulos, George E. and Basso, Daniela and and Soucek, Pavel and Brenner, Hermann and Lawlor, Rita T. and Morelli, and Luca and Ivanauskas, Audrius and Kauffmann, Emanuele Federico and and Macauda, Angelica and Gazouli, Maria and Archibugi, Livia and Nentwich, and Michael and Cavestro, Giulia Martina and Vodicka, Pavel and Landi, and Stefano and Tavano, Francesca and Sperti, Cosimo and Hackert, Thilo and and Kupcinskas, Juozas and Pezzilli, Raffaele and Andriulli, Angelo and and Pollina, Luca and Kreivenaite, Edita and Gioffreda, Domenica and and Jamroziak, Krzysztof and Hegyi, Peter and Izbicki, Jakob R. and Testoni, and Sabrina Gloria Giulia and Zuppardo, Raffaella Alessia and Bozzato, Dania and and Neoptolemos, John P. and Malats, Nuria and Canzian, Federico and and Campa, Daniele and Lovecek, Martin",
    journal = "Journal of Carcinogenesis",
    year = "2021",
    volume = "42",
    number = "8",
    pages = "1037-1045",
    publisher = "Oxford University Press",
    issn = "1477-3163",
    doi = "10.1093/carcin/bgab057",
    abstract = "Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal
cancers. Its poor prognosis is predominantly due to the fact that most
patients remain asymptomatic until the disease reaches an advanced
stage, alongside the lack of early markers and screening strategies. A
better understanding of PDAC risk factors is essential for the
identification of groups at high risk in the population. Genome-wide
association studies (GWAS) have been a powerful tool for detecting
genetic variants associated with complex traits, including pancreatic
cancer. By exploiting functional and GWAS data, we investigated the
associations between polymorphisms affecting gene function in the
pancreas (expression quantitative trait loci, eQTLs) and PDAC risk. In a
two-phase approach, we analysed 13 713 PDAC cases and 43 784 controls
and identified a genome-wide significant association between the A
allele of the rs2035875 polymorphism and increased PDAC risk (P = 7.14 x
10(-10)). This allele is known to be associated with increased
expression in the pancreas of the keratin genes KRT8 and KRT18, whose
increased levels have been reported to correlate with various tumour
cell characteristics. Additionally, the A allele of the rs789744 variant
was associated with decreased risk of developing PDAC (P = 3.56 x
10(-6)). This single nucleotide polymorphism is situated in the SRGAP1
gene and the A allele is associated with higher expression of the gene,
which in turn inactivates the cyclin-dependent protein 42 (CDC42) gene
expression, thus decreasing the risk of PDAC. In conclusion, we present
here a functional-based novel PDAC risk locus and an additional strong
candidate supported by significant associations and plausible biological
mechanisms."
}