The screening protocol includes genetic counselling, transcutaneous abdominal ultrasound, magnetic resonance imaging, and blood collection and eligible participants included individuals with a family history of pancreatic cancer or BRCA2 mutation carriers.
We found that the TP53 Pro/Pro genotype compared to the Arg/Arg genotype had a profound effect on pancreatic cancer risk among males, particularly among heavy smokers and excessive alcohol drinkers.
These data support a role for p53 gene alterations in human pancreatic cancer, and suggest that loss of its regulatory functions may constitute one of the differences between pancreatic cancer and chronic pancreatitis.
Targeting defects in the DNA repair machinery of neoplastic cells, for example, those due to inactivating BRCA1 and/or BRCA2 mutations, has been used for developing new therapies in certain types of breast, ovarian and pancreatic cancers.
Through the biopsy histopathological examination, imaging examination, and genetic testing, the patient was diagnosed as metastatic PC with BRCA2 mutation.
Germline mutations of BRCA2 are predicted to account for approximately 35% of families with multiple case, early onset female breast cancer, and they are also associated with an increased risk of male breast cancer, ovarian cancer, prostate cancer and pancreatic cancer.
We found that the combination of AZD7762 and olaparib produced significant radiosensitization in p53 mutant pancreatic cancer cells and in all of the isogenic cancer cell lines.
Germline BRCA2 mutations predispose to ovarian, breast and pancreatic cancer, while a germline MRE11 mutation is associated with an ataxia telangiectasia-like disorder.
Since carriers of germline BRCA2 gene mutations have an increased risk of developing pancreatic cancer, the FA pathway has been investigated as a tumor suppressor pathway in pancreatic cancer.Recently van der Heijden et al. identified FANCC and FANCG gene mutations in patients with young-onset pancreatic cancer.
Using the whole-cell recording mode of the patch-clamp technique, functional ion channels were electrophysiologically characterized in PANC-1 (K-ras G12D (+/-), p53R273C, Deltap16), BxPC-3 (smad4-, p53 Y220C, Deltap16), and MiaPaCa-2 [transforming growth factor-beta receptor type II defect, K-ras G12C(-/-), p53R248W, Deltap16] human pancreatic cancer cell lines.
Our case is the first clinical piece of evidence that demonstrates an increased sensitivity to camptothecin-11 and a reduced topoisomerase I relaxation activity in BRCA2 associated pancreatic cancer.
Other factors which predicted the presence of a BRCA2 mutation included a case of breast cancer diagnosed at age 35 or below (P = 0.01) and a family history of pancreatic cancer (P = 0.03).
Germline mutations in the BRCA2, CDKN2A/p16, hMSH2, hMLH1, hPMS1, hPMS2, LKB1/STK1, and PRSS1 genes have been associated with increased risk for pancreatic cancer.
In particular, the relative risk to male BRCA2 mutation carriers is high before age 65 years, largely attributable to breast, prostate, and pancreatic cancers.
Therefore, we asked whether radiation sensitivity of pancreatic cancers developing in individuals with germline BRCA2 mutations can be enhanced by agents that inhibit poly (ADP-ribose) polymerase (PARP).
Previous small scale studies reported that deleterious BRCA2 and CDKN2a germline mutations contribute to a subset of families with inherited pancreatic cancer.