@article{3077719,
    title = "Germline BRCA2 K3326X and CHEK2 I157T mutations increase risk for sporadic pancreatic ductal adenocarcinoma",
    author = "Obazee, O. and Archibugi, L. and Andriulli, A. and Soucek, P. and Małecka-Panas, E. and Ivanauskas, A. and Johnson, T. and Gazouli, M. and Pausch, T. and Lawlor, R.T. and Cavestro, G.M. and Milanetto, A.C. and Di Leo, M. and Pasquali, C. and Hegyi, P. and Szentesi, A. and Radu, C.E. and Gheorghe, C. and Theodoropoulos, G.E. and Bergmann, F. and Brenner, H. and Vodickova, L. and Katzke, V. and Campa, D. and Strobel, O. and Kaiser, J. and Pezzilli, R. and Federici, F. and Mohelnikova-Duchonova, B. and Boggi, U. and Lemstrova, R. and Johansen, J.S. and Bojesen, S.E. and Chen, I. and Jensen, B.V. and Capurso, G. and Pazienza, V. and Dervenis, C. and Sperti, C. and Mambrini, A. and Hackert, T. and Kaaks, R. and Basso, D. and Talar-Wojnarowska, R. and Maiello, E. and Izbicki, J.R. and Cuk, K. and Saum, K.U. and Cantore, M. and Kupcinskas, J. and Palmieri, O. and Delle Fave, G. and Landi, S. and Salvia, R. and Fogar, P. and Vashist, Y.K. and Scarpa, A. and Vodicka, P. and Tjaden, C. and Iskierka-Jazdzewska, E. and Canzian, F.",
    journal = "International Journal  of Cancer",
    year = "2019",
    volume = "145",
    number = "3",
    pages = "686-693",
    publisher = "Wiley-Liss, Inc.",
    issn = "0020-7136",
    doi = "10.1002/ijc.32127",
    keywords = "checkpoint kinase 2;  DNA;  lysine;  threonine;  BRCA2 protein;  BRCA2 protein, human;  checkpoint kinase 2;  CHEK2 protein, human, adult;  age;  aged;  Article;  cancer risk;  CHEK2 gene;  controlled study;  female;  gene mutation;  genetic association;  genetic risk;  genotype;  germ line;  human;  major clinical study;  male;  pancreas adenocarcinoma;  population research;  priority journal;  risk factor;  sex;  tumor suppressor gene;  case control study;  genetic predisposition;  genetics;  germline mutation;  middle aged;  pancreas carcinoma;  pancreas tumor;  single nucleotide polymorphism, Aged;  BRCA2 Protein;  Carcinoma, Pancreatic Ductal;  Case-Control Studies;  Checkpoint Kinase 2;  Female;  Genes, BRCA2;  Genetic Predisposition to Disease;  Germ-Line Mutation;  Humans;  Male;  Middle Aged;  Pancreatic Neoplasms;  Polymorphism, Single Nucleotide",
    abstract = "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) consortium. Risk estimates were evaluated using multivariate unconditional logistic regression with adjustment for possible confounders such as sex, age and country of origin. Statistical analyses were two-sided with p values <0.05 considered significant. K3326X and I157T were associated with increased risk of developing sporadic PDAC (odds ratio (ORdom) = 1.78, 95% confidence interval (CI) = 1.26–2.52, p = 1.19 × 10−3 and ORdom = 1.74, 95% CI = 1.15–2.63, p = 8.57 × 10−3, respectively). Neither mutation was significantly associated with risk of developing early-onset PDAC. This retrospective study demonstrates novel risk estimates of K3326X and I157T in sporadic PDAC which suggest that upon validation and in combination with other established genetic and non-genetic risk factors, these mutations may be used to improve pancreatic cancer risk assessment in European populations. Identification of carriers of these risk alleles as high-risk groups may also facilitate screening or prevention strategies for such individuals, regardless of family history. © 2019 UICC"
}