The risk of developing papillary thyroid carcinoma (PTC), the most frequent form of thyroid malignancy, is elevated up to 8.6-fold in first-degree relatives of PTC patients. The familial risk could be explained by high-penetrance mutations in yet unidentified genes, or polygenic action of low-penetrance alleles. Since the DNA-damaging exposure to ionizing radiation is a known risk factor for thyroid cancer, polymorphisms in DNA repair genes are likely to affect this risk. In a search for low-penetrance susceptibility alleles we employed Sequenom technology to genotype deleterious polymorphisms in ATM, CHEK2, and BRCA1 in 1,781 PTC patients and 2,081 healthy controls. As a result of the study, we identified CHEK2 rs17879961 (OR = 2.2, P = 2.37e-10) and BRCA1 rs16941 (odds ratio [OR] = 1.16, P = 0.005) as risk alleles for PTC. The ATM rs1801516 variant modifies the risk associated with the BRCA1 variant by 0.78 (P = 0.02). Both the ATM and BRCA1 variants modify the impact of male gender on clinical variables: T status (P = 0.007), N status (P = 0.05), and stage (P = 0.035). Our findings implicate an important role of variants in the ATM- CHEK2- BRCA1 axis in modification of the genetic predisposition to PTC and its clinical manifestations.

<50 3269 (70.79%) First operator, n (%) Specialist 2589 (56.06%) Resident 2029 (43.94%) Median operative time, min (IQR) 55 (40-70) Technique, n (%) Clipping 2841 (61.64%) Suturing/ligature 453 (9.79%) Stapler 313 (6.75%) Endoloop 606 (13.11%) Röder loop 403 (8.71%) Complicated appendicitis, n (%) 1269 (27.48%) Uncomplicated appendicitis, n (%) 3349 (72.52%) Intraoperative adverse events, n (%) 104 (2.25%) Drainage, n (%) 3493 (75.64%) Postoperative morbidity, n (%) 310 (6.71%) Clavien-Dindo classification of surgical complications, n (%) I 146 (3.16%) II 80 (1.73%) III 77 (1.67%) IV 4 (0.09%) V 3 (0.06%) Conversions, n (%) 294 (6.37%) Reinterventions after primary procedure, n (%) 98 (2.12%) LOS 3 (2-4) Readmissions, n (%) 118 (2.56%)

Purpose: Five germline genetic variants (rs116909374, rs965513, rs944289, rs966423, and rs2439302) have been associated in genome-wide association studies (GWAS) with increased risk of differentiated thyroid cancer (DTC), but their role in mortality of patients has not been established. Also, no preoperative marker of the clinical outcome of thyroid cancer had yet been identified. The aim of the study was to investigate the relationship between the variants and overall mortality in patients with DTC.Experimental Design: Retrospective study of 1,836 patients (1,643 women, 193 men) with median age at diagnosis of 49 years and overall median follow-up time of 8.7 years after initial treatment at a single comprehensive cancer center between 1990 and 2013.Results: Among 5 variants, rs966423 was associated with increased mortality, which was 6.4% (33 of 518) versus 3.7% (47 of 1,259) in TT carriers versus CC/CT carriers (P ¼ 0.017). The HR of TT versus TC/CC carriers was 1.6 [95% confidence interval (CI), 1.02-2.49; P ¼ 0.038] after adjustment for age at diagnosis and sex. Importantly, the association of rs966423 with mortality remained valid when clinicopathologic risk factors were included in the model (HR, 1.89; 95% CI, 1.14-3.13; P ¼ 0.014). Higher rs966423-associated patient mortality of TT versus CC/CT carriers was also observed in interaction with angioinvasion (adjusted HR, 3.48; 95% CI, 1.67-7.22; P < 0.001), lymph node metastasis (adjusted HR, 3.47; 95% CI, 1.16-10.4; P ¼ 0.018), extrathyroidal invasion (adjusted HR, 2.07; 95% CI, 1.15-3.73; P ¼ 0.013).Conclusions: The presence of the rs966423-TT genotype was associated with a significant increase in overall mortality of patients with DTC. Contrary to BRAF mutation and other somatic changes, the status of germline rs966423 is known before the treatment and might be used in the management of mortality risk by means of modification of therapy.

The risk of developing papillary thyroid carcinoma (PTC), the most frequent form of thyroid malignancy, is elevated up to 8.6-fold in first-degree relatives of PTC patients. The familial risk could be explained by high-penetrance mutations in yet unidentified genes, or polygenic action of low-penetrance alleles. Since the DNA-damaging exposure to ionizing radiation is a known risk factor for thyroid cancer, polymorphisms in DNA repair genes are likely to affect this risk. In a search for low-penetrance susceptibility alleles we employed Sequenom technology to genotype deleterious polymorphisms in ATM, CHEK2, and BRCA1 in 1,781 PTC patients and 2,081 healthy controls. As a result of the study, we identified CHEK2 rs17879961 (OR 5 2.2, P 5 2.37e-10) and BRCA1 rs16941 (odds ratio [OR] 5 1.16, P 5 0.005) as risk alleles for PTC. The ATM rs1801516 variant modifies the risk associated with the BRCA1 variant by 0.78 (P 5 0.02). Both the ATM and BRCA1 variants modify the impact of male gender on clinical variables: T status (P 5 0.007), N status (P 5 0.05), and stage (P 5 0.035). Our findings implicate an important role of variants in the ATM-CHEK2-BRCA1 axis in modification of the genetic predisposition to PTC and its clinical manifestations.

In a New Keynesian model with asymmetric information we show that publication of macroeconomic projections and of the future interest rate path by the central bank can improve macroeconomic outcomes. However, the gains from publishing interest rate paths are small relative to those from publishing macroeconomic projections. Given that most inflation targeting central banks are already publishing macroeconomic projections this means that most gains from increasing transparency in this area may already have been reaped. This, together with the potential costs, may explain the relative reluctance of central banks to publish interest rate paths.JEL: E52, E58, E43 Keywords: interest rate path, monetary policy, adaptive learning * We would like to thank P.Soderlind, J.Suda, P.Welz and J.C.Williams as well as participants of the WIEM 2008 conference for helpful comments. The views expressed in this paper are our own and do not necessarily reflect the position of the National Bank of Poland.