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Ataxia Telangiectasia Mutated (ATM) gene helps to repair DNA damage and that increased cancer risks are associated with having a mutation in an ATM gene. ATM gene is newer compared to other known hereditary cancer genes. We present a rare care of 66-year-old female with extensive personal and family history of breast and pancreatic cancer had negative imaging surveillance until recent systemic imaging showed new pancreatic head 2.5x2.5 cm mass. Endoscopic ultrasound confirmed invasion of superior mesenteric vein with near confluence. No regional adenopathy was seen. She was felt to be borderline resectable and neoadjuavant chemotherapy was planned. She had a personal history of right breast cancer diagnosed in 1998 status post lumpectomy and axillary lymph node dissection and adjuvant chemotherapy with CMF regimen x 5 cycles and radiation therapy and endocrine therapy with tamoxifen for 5 years. In 2011 she was also diagnosed with rectal well to moderately differentiated adenocarcinoma status post abdominoperitoneal resection on 3/15/2011, 36 lymph nodes were negative, but the surgical circumferential radial margin was positive. She underwent adjuvant radiation therapy with total dose of 45 Gy. There was recurrence in vaginal and bladder wall adenocarcinoma in 2014 for which patient underwent an anterior exenteration. Pathology felt this was endocervical origin of malignancy and patient received megace therapy for 3 years based on hormone receptor positive status. For new diagnosis of pancreatic adenocarcinoma, she was started on Gemcitabine and Abraxane chemotherapy. Given extensive personal and family history of malignancy, she was referred to genetic counsellor. Hereditary cancers panel at invitae laboratory was positive for a heterozygous pathological variant in the ATM gene deletion (exons 62-63). ATM gene is associated with an increased risk for autosomal dominant breast, pancreatic and prostate cancer. Close relatives (children, siblings, and each parent) have up to a 50% chance of being a carrier of this variant. It is essential for treating physicians to educate patients and family members on the risk for subsequent malignancies.

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Background: Complications related to peritoneal dialysis (PD) in patients with autosomal-dominant polycystic kidney disease (ADPKD), including intraperitoneal rupture of renal cyst, hernia, membrane failure and peritonitis, have been reported. However, long-term clinical outcomes of ADPKD patients on PD remain unclear. We performed this meta-analysis to assess the risks of death, technique failure and peritonitis in ADPKD patients on PD. Methods: A systematic review was conducted using MEDLINE, EMBASE and Cochrane databases from inception to October 2017 to identify studies that evaluated the outcomes of ADPKD patients on PD, including the risks of death, technique failure and peritonitis. Non-ADPKD patients on PD were used as controls. Effect estimates from the individual study were extracted and combined using the random-effect, generic inverse variance method of DerSimonian and Laird. Results: Twelve cohort studies with a total of 14 673 patients on PD (931 ADPKD and 13 742 non-ADPKD patients) were enrolled. Compared with non-ADPKD status, ADPKD was associated with significantly decreased mortality risk with pooled odds ratio (OR) of 0.68 (95% confidence interval (CI), 0.53–0.86; I 2 = 0). There were no associations of ADPKD with the risks of technique failure of PD and peritonitis with pooled OR of 0.93 (95% CI, 0.79–1.10; I 2 = 0) and 0.88 (95% CI, 0.75–1.05; I 2 = 0), respectively. We found no publication bias as assessed by Egger's regression asymmetry test, with P = 0.90, 0.28 and 0.60 for the risks of mortality, technique failure and peritonitis in ADPKD patients on PD, respectively. Conclusion: Compared with non-ADPKD patients on PD, our study demonstrates that ADPKD patients on PD have 0.68-fold decreased mortality risk. There are no associations of ADPKD status with the risks of technique failure or peritonitis.

Gardner's syndrome is an autosomal dominant disease presenting multiple colonic polyps with a predisposition for malignant change. In addition to colonic polyp formation by early adolescence, extracolonic lesions appear often prior to polyp formation. One theoretical mechanism for the origin of polyps and malignancies in Gardner's syndrome is a genetic defect in the natural killer cell activity of patients with this disease. Natural killer cells are a of lymphocytes that spontaneously lyse tumor cells subpopulation and virally transformed cells. A study was undertaken to determine the natural killer activity of patients with Gardner's syndrome .

Polycystic kidney disease is an inherited degenerative disease in which the uriniferous tubules are replaced by expanding fluid-filled cysts that ultimately destroy organ function. Autosomal dominant polycystic kidney disease (ADPKD) is the most common form, afflicting approximately 1 in 1,000 people. It primarily is caused by mutations in the transmembrane proteins Polycystin-1 (PKD1) and Polycystin-2 (PKD2). The most proximal effects of polycystin mutations leading to cyst formation are not known, but pro-proliferative signaling must be involved for the tubule epithelial cells to increase in number over time. The stress-activated mitogen-activated protein kinase (MAPK) pathway c-Jun N-terminal kinase (JNK) promotes proliferation in specific contexts and is activated in acute and chronic kidney disease. Previous work found evidence of JNK activation in cystic tissues (Le et al., 2005) and others showed that JNK signaling is activated by aberrant expression of PKD1 and PKD2 in cell culture (Arnould et al., 1998; Arnould et al., 1999; Parnell et al., 2002; Yu et al., 2010) but the contribution of JNK signaling to cystic disease in vivo has not been investigated. This body of work describes the use of conditional and germline deletion of Pkd2, Jnk1 and Jnk2 to model ADPKD and JNK signaling inhibition in juvenile and adult mice. Immunoblots and histological staining were used to measure JNK activation and evaluate the effect of JNK deletion on cystic disease. Results show that Pkd2 deletion activated JNK signaling in juvenile and adult mice. Reduction of JNK activity significantly reduced cystic burden in kidneys of juvenile Pkd2 mutant mice. This correlated with reduced tubule cell proliferation and reduced kidney fibrosis. The improvement in cystic phenotype was driven primarily by Jnk1 deletion rather than Jnk2. JNK signaling inhibition in adult Pkd2 mutants significantly reduced liver cysts when mice were aged six months. JNK inhibition reduces the severity of cystic disease caused by the loss of Pkd2 suggesting that the JNK pathway should be explored as a potential therapeutic target for ADPKD.