PTEN as a Prognostic and Predictive Marker in Postoperative Radiotherapy for Squamous Cell Cancer of the Head and Neck

BACKGROUND: Tumor suppressor PTEN is known to control a variety of processes related to cell survival, proliferation, and growth. PTEN expression is considered as a prognostic factor in some human neoplasms like breast, prostate, and thyroid cancer. METHODOLOGY/PRINCIPAL FINDINGS: In this study we analyzed the influence of PTEN expression on the outcome of a randomized clinical trial of conventional versus 7-days-a-week postoperative radiotherapy for squamous cell cancer of the head and neck. The patients with cancer of the oral cavity, oropharynx, and larynx were randomized to receive 63 Gy in fractions of 1.8 Gy given 5 days a week (CF) or 7 days a week (p-CAIR). Out of 279 patients enrolled in the study, 147 paraffin blocks were available for an immunohistochemical assessment of PTEN. To evaluate the prognostic value of PTEN expression and the effect of fractionation relative to PTEN, the data on the outcome of a randomized clinical trial were analyzed. Tumors with a high intensity of PTEN staining had significant gain in the loco-regional control (LRC) from p-CAIR (5-year LRC 92.7% vs. 70.8%, for p-CAIR vs. CF, p = 0.016, RR = 0.26). By contrast, tumors with low intensity of PTEN did not gain from p-CAIR (5-year LRC 56.2% vs. 47.2%, p = 0.49, RR = 0.94). The intensity of PTEN highly affected the LRC in a whole group of 147 patients (5-year LRC 80.9% vs. 52.3% for high vs. low PTEN, p = 0.0007, RR = 0.32). In multivariate Cox analysis, including neck node involvement, EGFR, nm23, Ki-67, p53, cyclin D1, tumor site and margins, PTEN remained an independent predictor of LRC (RR = 2.8 p = 0.004). CONCLUSIONS/SIGNIFICANCE: These results suggest that PTEN may serve as a potent prognostic and predictive marker in postoperative radiotherapy for high-risk squamous cell cancer of the head and neck

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

Comparison of 6q25 Breast Cancer Hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC)

Peer reviewe

Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers

Abstract Introduction Several common alleles have been shown to be associated with breast and/or ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Recent genome-wide association studies of breast cancer have identified eight additional breast cancer susceptibility loci: rs1011970 (9p21, CDKN2A/B), rs10995190 (ZNF365), rs704010 (ZMIZ1), rs2380205 (10p15), rs614367 (11q13), rs1292011 (12q24), rs10771399 (12p11 near PTHLH) and rs865686 (9q31.2). Methods To evaluate whether these single nucleotide polymorphisms (SNPs) are associated with breast cancer risk for BRCA1 and BRCA2 carriers, we genotyped these SNPs in 12,599 BRCA1 and 7,132 BRCA2 mutation carriers and analysed the associations with breast cancer risk within a retrospective likelihood framework. Results Only SNP rs10771399 near PTHLH was associated with breast cancer risk for BRCA1 mutation carriers (per-allele hazard ratio (HR) = 0.87, 95% CI: 0.81 to 0.94, P-trend = 3 × 10-4). The association was restricted to mutations proven or predicted to lead to absence of protein expression (HR = 0.82, 95% CI: 0.74 to 0.90, P-trend = 3.1 × 10-5, P-difference = 0.03). Four SNPs were associated with the risk of breast cancer for BRCA2 mutation carriers: rs10995190, P-trend = 0.015; rs1011970, P-trend = 0.048; rs865686, 2df-P = 0.007; rs1292011 2df-P = 0.03. rs10771399 (PTHLH) was predominantly associated with estrogen receptor (ER)-negative breast cancer for BRCA1 mutation carriers (HR = 0.81, 95% CI: 0.74 to 0.90, P-trend = 4 × 10-5) and there was marginal evidence of association with ER-negative breast cancer for BRCA2 mutation carriers (HR = 0.78, 95% CI: 0.62 to 1.00, P-trend = 0.049). Conclusions The present findings, in combination with previously identified modifiers of risk, will ultimately lead to more accurate risk prediction and an improved understanding of the disease etiology in BRCA1 and BRCA2 mutation carriers

Analysis of variability of plasma leptin and lipids concentration in relations to glycolytic potential, intramuscular fat and meat quality in P76 pigs

International audienceThe aim of the study was the analyse of the variability and relationship between plasma leptin and lipids concentration, glycolytic potential, intramuscular fat and meat quality in P76-PenArLan hybrids pigs. The research was carried out on 30 pigs (18 boars and 12 gilts). In blood plasma, taken in vivo, leptin, triglycerides, total and HDL cholesterol were measured. Slaughter value of carcass was evaluated by CGM apparatus. On the basis of pH value, meat colour and natural drip loss, meat quality was estimated. Intramuscular fat and glycolytic potential was also determined. Obtained results showed a signifi cant inversely relationship between: a. plasma leptin level and backfat thickness and b. between intramuscular fat and glycolytic potential in muscle. Cluster analysis showed that studied pigs had been divided into three metabolic type groups differed signifi cantly in plasma leptin, triglycerides, total and LDL cholesterol concentration, backfat thickness, glycolytic potential and drip loss

Analysis of variability of plasma leptin and lipids concentration in relations to glycolytic potential, intramuscular fat and meat quality in P76 pigs

International audienceThe aim of the study was the analyse of the variability and relationship between plasma leptin and lipids concentration, glycolytic potential, intramuscular fat and meat quality in P76-PenArLan hybrids pigs. The research was carried out on 30 pigs (18 boars and 12 gilts). In blood plasma, taken in vivo, leptin, triglycerides, total and HDL cholesterol were measured. Slaughter value of carcass was evaluated by CGM apparatus. On the basis of pH value, meat colour and natural drip loss, meat quality was estimated. Intramuscular fat and glycolytic potential was also determined. Obtained results showed a signifi cant inversely relationship between: a. plasma leptin level and backfat thickness and b. between intramuscular fat and glycolytic potential in muscle. Cluster analysis showed that studied pigs had been divided into three metabolic type groups differed signifi cantly in plasma leptin, triglycerides, total and LDL cholesterol concentration, backfat thickness, glycolytic potential and drip loss

The prototype dosimetry system to protect MPD electronic equipment at the new NICA collider

The Multi-Purpose Detector (MPD) is a main detection system of the new collider located in Dubna, Russia (Nuclotron-based Ion Collider fAcility -NICA). During the work, the Slow Control electronic equipment which is located on the MPD surface and on the special platform near the MPD body, an accidental irradiation caused by the NICA’s failure or its abnormal functioning may occur. Thus, there is a risk of destroying the electronics by a radiation exposure in the platform area, and in the consequence the emergency/fast switch off of the MPD sub-detectors might become impossible. We present the preliminary dosimetry system i.e. the method of prevention of such situation by the continuous monitoring on the Slow Control electronics on the platform. System will be alarming when the radiation levels threshold will be surpassed

The prototype dosimetry system to protect MPD electronic equipment at the new NICA collider

The Multi-Purpose Detector (MPD) is a main detection system of the new collider located in Dubna, Russia (Nuclotron-based Ion Collider fAcility -NICA). During the work, the Slow Control electronic equipment which is located on the MPD surface and on the special platform near the MPD body, an accidental irradiation caused by the NICA’s failure or its abnormal functioning may occur. Thus, there is a risk of destroying the electronics by a radiation exposure in the platform area, and in the consequence the emergency/fast switch off of the MPD sub-detectors might become impossible. We present the preliminary dosimetry system i.e. the method of prevention of such situation by the continuous monitoring on the Slow Control electronics on the platform. System will be alarming when the radiation levels threshold will be surpassed

Trends in incidence and mortality of gynecological and breast cancers in Poland (1980-2018)

BACKGROUND: This study aimed to analyze and determine the incidence and mortality trends in gynecological and breast cancers (BCs) in Poland. The gynecological cancers assessed were cervical cancer (CC), corpus uteri cancer (CUC), ovarian cancer (OC), vaginal cancer (VAC), and vulvar cancer (VUC). PATIENTS AND METHODS: Data concerning the incidence and mortality for the period of 1980–2018 were obtained from the Polish National Cancer Registry (PNCR). Joinpoint regression analysis was performed to identify trends, which were described using the annual percentage change (APC) and the average annual percent change (AAPC). RESULTS: Statistically significant increases were observed in BC incidence (AAPC: 2.3; CI: 1.8 to 2.9; p<0.05), CUC incidence (AAPC: 2.3; CI: 1.9 to 2.7; p<0.05), CUC mortality (AAPC: 0.4; CI: 0.1 to 0.7; p<0.05) and VUC mortality (AAPC: 1.16, CI: 0.1 to 2.2; p<0.05). VAC mortality decreased (AAPC: −3.5, CI: −5.0 to –2.0; p<0.05), as did CC incidence and mortality (AAPC: −2.1, CI: −2.3 to −1.8; p<0.05, AAPC: −2.0, CI: −2.2 to –1.8; p<0.05, respectively). Between 1980 and 1993, OC incidence initially increased and then stabilized (AAPC: 0.9; CI: 0.7 to 1.1; p<0.05). After 2007, OC mortality decreased (AAPC: 0.0; CI: −0.2 to 0.2; p=0.8). Trends in VUC and VAC incidence and BC mortality were not statistically significant. CONCLUSION: The results of this study showed a significant increase in OC, CUC, and BC incidence, and a decrease in the incidence of CC and VAC. The VUC trends were stable. Mortality trends for BC initially fluctuated and, since 2010, has begun to increase. Throughout the observed period, mortality due to VUC and CUC increased, whereas decreased among patients with CC. OC mortality was stable, but not significant. Furthermore, the study showed a correlation between age group and rate of incidence and mortality of each assessed cancer