Expression and Clinicopathologic Significance of Proteolysis-Inducing Factor in Non–Small-Cell Lung Cancer: An Immunohistochemical Analysis

BackgroundProteolysis-inducing factor (PIF) is a 24-kD glycoprotein that has been identified in mice and in humans with cancer cachexia. The PIF is a putative mediator of cancer-associated weight loss, which induces atrophy of skeletal muscle.Materials and MethodsIn this study, we detected the expression of the PIF in 71 patients with non–small-cell lung cancer (NSCLC) and 10 patients with healthy lung tissues as a control group using the immunohistochemical staining method. In addition, weight loss of patients and serum carcinoembryonic antigen (CEA) and cytokeratin fragment antigen 21-1 (CYFRA 21-1) were measured, and an analysis of overall survival was done.ResultsProteolysis-inducing factor was expressed in only 56.3% (40/71) of lung cancers and not in normal tissue. The positive rate of the PIF expression was significantly higher (P < .01) in patients with weight loss than in those without weight loss. There was no significant relationship (P > .05) between the PIF expression and the histology type, degree of differentiation, or tumor clinical stages in lung cancers. The sensitivity of the PIF was better than that of CEA (P < .05), but similar to that of CYFRA 21-1 in NSCLC.ConclusionProteolysis-inducing factor expression was negatively related to the survival of patients with NSCLC in the medium to advanced stages (II-IV). There was a significant correlation between weight loss and survival in the PIF-positive patients.     

Changes over three decades in outcome and the prognostic influence of age-at-diagnosis in young patients with neuroblastoma: a report from the International Neuroblastoma Risk Group Project

Purpose

Increasing age has been an adverse risk factor in children with neuroblastoma (NB) since the 1970’s, with a 12-month age-at-diagnosis cut-off for treatment stratification. Over the last 30 years, treatment intensity for children >12 months with advanced-stage disease has increased; to investigate if this strategy has improved outcome and/or reduced the prognostic influence of age, we analysed the International Neuroblastoma Risk Group (INRG) database.

Patients and methods

Data from 11,037 children with NB (1974-2002) from Australia, Europe, Japan, North America. Cox modelling of event-free survival (EFS) tested if the era and prognostic significance of age-of-diagnosis, adjusted for bone marrow (BM) metastases and MYCN status, effects on outcome had changed.

Results

Outcome improved over time: 3-year EFS 46% (1974-1989) and 71% (1997-2002). The risk for those >18 months against ?12 decreased: hazard ratio (HR); 4.61 and 3.94. For age 13-18 months, EFS increased from 42% to 77%. Outcome was worse if: >18 months (HR 4.47); BM metastases (HR 4.00); and MYCN amplified (HR 3.97). For 1997-2002, the EFS for >18 months with BM involvement and MYCN amplification was 18%, but 89% for 0-12 months with neither BM involvement nor MYCN amplification.

Conclusions

There is clear evidence for improving outcomes for children with NB over calendar time. The adverse influence of increasing age-at-diagnosis has declined but it remains a powerful indicator of unfavourable prognosis. These results support the age-of-diagnosis cut-off of greater than 18 months as a risk criterion in the INRG classification system.     

Parity and the risk of pancreatic cancer: A nested case-control study

Smoking is the only generally accepted risk factor for pancreatic cancer. Reproductive history has in recent studies been associated with pancreatic cancer, but with contradictory results. In order to evaluate a possible association between age at first birth and the number of births and pancreatic cancer, we conducted a nested case-control study by linking 2 Swedish nationwide registries: the Cancer Registry and The Fertility Registry. Among women born between 1925 and 1970, 1,015 patients with pancreatic cancer were compared with 5,073 age-matched controls. No association between pancreatic cancer and number of births was found. Age at first birth was inversely related with the risk of pancreatic cancer (OR per 5 years = 0.90; 95% CI 0.83<0R>–<0B>0.97; p<0B> = 0.01), an association mainly confined to women with a diagnosis of pancreatic cancer before 50 years of age (OR per 5 years = 0.85; 95% CI 0.73<0R>–<0B>1.00; p<0B> = 0.04). This trend remained after adjustment for parity, but was less prominent. Young age at first birth and high parity in Sweden are, however, associated with an increased frequency of smoking, thus at least some of the increased risk for pancreatic cancer in women with young age at first birth is likely to be explained by smoking acting as a confounder. Int. J. Cancer 77:224–227, 1998. © 1998 Wiley-Liss, Inc.     

Reproductive and gynecological complication risks among thyroid cancer survivors

Purpose

Thyroid cancer is the most rapidly increasing cancer in the USA, affects a young, mostly female population, and has high survival. The aim of this study was to determine if there is an increased risk of reproductive system adverse events or pregnancy complications among women diagnosed with thyroid cancer under the age of 50.

Methods

Up to five female cancer-free individuals were matched to each female thyroid cancer survivor diagnosed before the age of 50 based on birth year, birth state, and follow-up time, within the Utah Population Database. Medical records were used to identify disease diagnoses stratified over three time periods: 0–1, >?1–5, and >?5–10 years after cancer diagnosis. Cox proportional hazards models were used to estimate hazard ratios (HR) with adjustment on matching factors, race, BMI, and Charlson Comorbidity Index.

Results

There were 1832 thyroid cancer survivors and 7921 matched individuals. Thyroid cancer survivors had higher rates of having multiple health conditions associated with the gynecological system (15.4% vs. 9.4%) and pregnancy (14.3% vs 9.5%) >?1–5 years after cancer diagnosis. Increased risks persisted >?5–10 years after cancer diagnosis for menopausal disorders (HR?=?1.78, 99% CI?=?1.37, 2.33) and complications related to pregnancy (HR?=?2.13, 99% CI?=?1.14, 3.98). Stratified analyses showed these risks remained increased across different treatment types.

Conclusions

There were significant risk increases in reproductive system and pregnancy complications among female thyroid cancer survivors within this study.

Implications for Cancer Survivors

Although radiation has been linked to reproductive risks in previous studies, we found risks were increased in patients regardless of treatment.

     

A Pharmacokinetic Study Evaluating the Relationship Between Treatment Efficacy and Incidence of Adverse Events with Thalidomide Plasma Concentrations in Patients with Refractory Multiple Myeloma

BackgroundMultiple myeloma (MM) is a clonal disorder of plasma cells, accounting for 10% of hematologic malignancies. Relapsed or refractory MM has a poor prsognosis. Thalidomide has been reported to be effective for these patients; however, high-dose thalidomide has induced many adverse events, including in the nervous, gastrointestinal, and hematopoietic systems in approximately 20%-50% of patients. Recently, low-dose thalidomide therapy has been used in many countries in order to reduce these adverse events. The objective of this study was to determine whether plasma concentration of thalidomide is related to the efficacy and the development of adverse events in patients with refractory MM treated with low-dose thalidomide plus low-dose dexamethasone.Patients and MethodsA total of 66 patients (age range, 40-74 years) presenting with progressive disease after previous treatments were treated with low-dose thalidomide and low-dose dexamethasone. Thalidomide was administered orally at 100 mg/day for the first week. When severe adverse events did not develop, the dose was increased to 200 mg/day in the second week and was continued until progression. Dexamethasone was administered at a dose of 4 mg/day for the first 4 weeks, then decreased by 1 mg every week, and finally maintained at 1 mg/day. Plasma trough concentration of thalidomide 3 days after thalidomide treatment was analyzed by high-performance liquid chromatography in 45 patients (age range, 42-74 years) who agreed to participate in this study of thalidomide concentration analysis.ResultsThe mean concentrations at 100 mg/day and 200 mg/day were 0.343 μg/mL (range, 0.05-1.45 μg/mL) and 0.875 μg/mL (range, 0.19-2.09 μg/mL), respectively. The overall response rate (near-complete response + partial response + minimal response) of this treatment was 73%. Five had stable disease, and 3 patients experienced progressive disease. There was no relationship between the concentration of thalidomide in the plasma and the efficacy (P > .8). Severe adverse events, including grade > 2 nonhematologic and grade > 3 hematologic adverse events, were observed in 21 patients (46.6%). There was no significant difference in the concentration of thalidomide between the patients with and without severe adverse events (P > .843).ConclusionThe thalidomide concentration in the plasma does not predict treatment efficacy and the development of adverse events.     

Correlation between overall survival and growth modulation index in pre-treated sarcoma patients: a study from the French Sarcoma Group

BackgroundGrowth modulation index (GMI), the ratio of two times to progression measured in patients receiving two successive treatments (GMI = TTP2/TTP1), has been proposed as a criterion of phase II clinical trials. Nevertheless, its use has been limited until now.Patients and methodsWe carried out a retrospective multicentre study in soft tissue sarcoma patients receiving a second-line treatment after doxorubicin-based regimens to evaluate the link between overall survival and GMI. Second-line treatments were classified as ‘active’ according to the EORTC-STBSG criteria (3-month progression-free rate >40% or 6-month PFR >14%). Comparisons used chi-squared and log-rank tests.ResultsThe population consisted in 106 men and 121 women, 110 patients (48%) received ‘active drugs’. Median OS from the second-line start was 317 days. Sixty-nine patients experienced GMI >1.33 (30.4%). Treatments with ‘active drug’ were not associated with OS improvement: 490 versus 407 days (P = 0.524). Median OS was highly correlated with GMI: 324, 302 and 710 days with GMI <1, GMI = [1.00–1.33], and GMI >1.33, respectively (P < 0.0001). In logistic regression analysis, the sole predictive factor was the number of doxorubicin-based chemotherapy cycles.ConclusionGMI seems to be an interesting end point that provides additional information compared with classical criteria. GMI >1.33 is associated with significant OS improvement.     

Knowledge and Prevention Practices Before Breast Cancer Diagnosis in a Cross-Sectional Study Among Survivors: Impact on Patients’ Involvement in the Decision Making Process

Disparities exist in breast cancer knowledge and education, which tend to influence symptom interpretation and decision to seek screening/care. The present project describes a cohort of women’s experiences, knowledge, and health behavior prior to and after a diagnosis of breast cancer. It also studies how knowledge and demographic factors are associated with level of involvement participants had in the treatment of their breast cancer. Women >18 years who have been diagnosed and treated for breast cancer within 10 years were recruited in Pittsburgh, PA, through the Healthy People Cohort Registry, a database of volunteers from the community, and Brooklyn, NY, through the American Cancer Society breast cancer survivor database. Subsequent to institutional ethics approval, a questionnaire was administered by mail and through an electronic interactive format. The study included 124 breast cancer survivors, one-quarter of whom were of African ancestry. Roughly half of the women indicated that their overall knowledge of breast cancer was limited before diagnosis; no significant association between overall knowledge before diagnosis and stage at diagnosis or an active role of the patient in treatment choices was observed. Two-third of the women reported using personal research on internet, books, and other media to increase knowledge on breast cancer after diagnosis; the improvement of knowledge was associated with an active role in therapy choice. White women’s self report of breast cancer knowledge prior to diagnosis was higher than that of women of African origin (p?=?0.03); the latter experienced more delays in getting results about the diagnosis (p?=?0.002), in starting treatment (p?=?0.03), and in having treatment available at local facilities (p?=?0.007) than white women. White women were more likely to improve their knowledge through their own research (p?=?0.08) and through the contribution of their physician (p?=?0.06) than women of African origin.There is still a need for addressing breast cancer knowledge among black women, and improvement in physician emotional support and in their contribution to the patient’s knowledge is necessary. These efforts may have a positive impact on breast cancer knowledge among black women in the US.     

Quantitative Analysis of Practice Size Consolidation in Radiation Oncology: A Trend Toward Bigger and Fewer Practices

PurposeThere is evidence of practice consolidation in US health care in recent years. To our knowledge, a detailed quantitative study of recent changes in radiation oncology practice size has not been performed. We aim to evaluate radiation oncology practice size changes between 2012 and 2020 in the United States.Materials and MethodsUsing the Medicare Physician Compare Database, we identified practices employing radiation oncologists using their taxpayer identification number and individual radiation oncologists using their national provider identifier. We grouped individual radiation oncologists into categories by practice size (which includes the number of physicians of all specialties) and compared the number of radiation oncologists in each category between 2012 and 2020. Further analyses by US geographic census region, single-specialty practice, academic practice, and high- and low-population density areas were performed.ResultsBetween 2012 and 2020, the total number of practicing radiation oncologists increased by 9%, and the number of practices employing radiation oncologists decreased by 11.5%. The number of radiation oncologists in practices of size 1 to 2, 3 to 9, 10 to 24, and 25 to 49 decreased by 3.7%, 4.7%, 4.9%, and 2%, respectively, and the number of radiation oncologists in practices of size 50 to 99, 100 to 499, and 500+ increased by 1.4%, 2.1%, and 11.8%, respectively (all 500+ practices are multispecialty groups). The increase in practice size was significant in all regions, for single-specialty and multispecialty practices, academic and nonacademic practices, and for practices in high-, middle-, and low-population density areas (P < .05 for all comparisons). The proportion of single-specialty practices has decreased significantly (P < .001), and the proportion of academic practices increased significantly (P = .004). Additionally, the proportion of practices and physicians in high- and low-population density regions remained stable during this period (P > .05).ConclusionsOur analysis suggests that practice size consolidation has occurred within the US radiation oncology workforce from 2012 to 2020. The impact of this consolidation on quality, cost, and patient access deserves further attention.     

Factors Associated With Local Tumor Control and Complications After Thermal Ablation of Colorectal Cancer Liver Metastases: A 15-year Retrospective Cohort Study

IntroductionThe purpose of this study was to identify risk factors associated with local tumor progression-free survival (LTPFS) and complications after colorectal liver metastases (CLM) thermal ablation (TA).Patients and MethodsThis retrospective analysis included 286 patients with 415 CLM undergoing TA (radiofrequency and microwave ablation) in 378 procedures from January 2003 to July 2017. Prior hepatic artery infusion (HAI), bevacizumab, pre-existing biliary dilatation, ablation modality, minimal ablation margin (MM), prior hepatectomy, CLM number, and size were analyzed as factors influencing complications and LTPFS. Statistical analysis included the Kaplan-Meier method, Cox proportional hazards model, competing risk analysis, univariate/multivariate logistic/exact logistic regressions, and the Fisher exact test. Complications were reported according to modified Society of Interventional Radiology guidelines.ResultsThe median follow-up was 31 months. There was no LTP for MM > 10 mm. Smaller tumor size, increased MM, and prior hepatectomy correlated with longer LTPFS. The major complications occurred following 28 (7%) of 378 procedures. There were no biliary complications in HAI-naive patients, versus 11% in HAI patients (P < .001), of which 7% were major. Biliary complications predictors in HAI patients included biliary dilatation, bevacizumab, and MM > 10 mm. In HAI patients, ablation with 6 to 10 mm and > 10 mm MM resulted in major biliary complication rates of 4% and 21% (P = .0011), with corresponding LTP rates of 24% and 0% (P = .0033). In HAI-naive patients, the LTP rates for 6 to 10 mm and > 10 mm MM were 27% and 0%, respectively.ConclusionsNo LTP was seen for MM > 10 mm. Biliary complications occurred only in HAI patients, especially in those with biliary dilatation, bevacizumab, and MM > 10 mm. In HAI patients, MM of 6 to 10 mm resulted in 76% local tumor control and 4% major biliary complications incidence.     

Impact of Enlarged Nonhypermetabolic Lymph Nodes on Outcomes After Stereotactic Body Radiotherapy for Early-Stage Non–Small-Cell Lung Cancer

Background

Up to 15% of patients undergoing positron emission tomography (PET)/computed tomography (CT) before stereotactic body radiotherapy (SBRT) harbor occult nodal disease. In the absence of invasive mediastinal staging, the clinical significance of enlarged nonhypermetabolic lymph nodes (LNs) remains unclear. We performed what is to our knowledge the first study to address whether enlarged nonhypermetabolic LNs were associated with higher post-SBRT failure rates.

Radiation pneumonitis in pediatric Hodgkin lymphoma patients receiving radiation therapy to the chest

Purpose

The purpose of this study is to determine the incidence of radiation pneumonitis (RP) in children receiving radiation therapy (RT) for Hodgkin lymphoma (HL).

Serum levels of selenium in patients with breast cancer before and after treatment of external beam radiotherapy

BackgroundTo evaluate the influence of radiotherapy on the selenium serum levels of breast cancer patients.Patients and methodsThis prospective study includes 209 breast cancer patients treated by external beam radiotherapy from December 2007 until August 2008. Plasma selenium concentrations were determined before and at the end of the radiotherapeutic treatment. Age, clinical stage, prior chemotherapy, body mass index (BMI) and personal habits (smoking and alcoholism) were recorded for each patient.ResultsThe mean age was 61 years; the mean BMI was 28.7. One hundred and seventy-four patients (83.3%) were nonsmokers. One hundred and eighty-nine patients (90.4%) showed no drinking habits and 110 (52.6%) have no prior chemotherapy. Sixty patients (28.7%) were in clinical stage I, 141 (67.5%) in clinical stage II and 8 (3.8%) in clinical stage III. At the beginning of radiotherapy, the mean selenium value for all patients was 86.4 μg/l and after radiation this value dropped to 47.8 μg/l. Multivariate analysis showed statistically significant difference in the plasma selenium concentration before and after radiotherapy for age (P > 0.001), BMI (P > 0.001), smoking (P > 0.001), alcoholism (P > 0.001), chemotherapy (P > 0.001) and clinical stage (P > 0.001).ConclusionsSignificant reduction in plasma levels of selenium is recorded in patients undergoing radiotherapy, suggesting attention to the nutritional status of this micronutrient and other antioxidant agents.     

in vivo nitrosation of amidopyrine in humans: use of 'ethanol effect' for biological monitoring of N-nitrosodimethylamine in urine

Under normal conditions a possible N-nitrosodimethylamine formationin vivo cannot directly be monitored in urine due to high metabolicconversion rate (>99.9%). Own experiments showed an increasedexcretion rate (up to 2.4%) if ethanol was administered simultaneously.This model was used for monitoring experiments with repect toin vivo for mation of N-nitrosodimethylamine. Amidopyrine, asa compound which is easily nitrosated, was administered (singleoral dose of 500 mg) to volunteers. Under the influence of 20–30g ethanol it was possible to detect N-nitrosodimethylamine inurine. From negative control experiments it must be concludedthat this appearance of N-nitrosodimethylamine derives fromin vivo nitrosation of the drug. The amount excreted in urinevaried between 0.5 and 10 µg N-nitrosodimethylamine within8 h and seemed to be influenced by salivary nitrite concentrationswhich ranged from 5 to 220 p.p.m. NO₂^–. In comparisonwith earlier excretion studies in humans it can be assumed thatonly 1–2% of the originally formed nitrosamine was foundin urine. To our knowledge this is the first time that in vivoformation of N-nitrosodimethylamine was directly shown to occurin humans.     

ERBB2 gene as a potential therapeutic target in small bowel adenocarcinoma

Aim of the studySmall bowel adenocarcinoma (SBA) is a rare and aggressive tumour with poor outcomes. Because of its low incidence, the number prospective studies remains insufficient leading to poor knowledge and absence of standard of care. Aiming to better understand small bowel carcinogenesis we investigated the frequency of somatic mutations in a large data set of patients in more than 740 mutational hotspots among 46 genes.MethodsIn total, 83 SBA cases were selected from two European databases. The sequencing was performed using the Ion 316 Chip. Additionally we looked into ERBB2 expression and microsatellite instability (MSI) status.ResultsThe tumours most frequently were duodenal (47%) and stage ⩾3 (63%). Eight genes were mutated with a frequency >5%: KRAS, TP53, APC, SMAD4, PIK3CA, ERBB2, BRAF and FBXW7. ERBB2 alterations are present in 10 patients (12%) through mutations (7 cases) or amplifications (3 cases). ERBB2 mutations were significantly associated with duodenal tumour location (P = 0.04). In this group, there was a positive association with dMMR status (P = 0.006) and APC mutation (P = 0.02) but negative association with p53 mutations (P = 0.038).ConclusionsThis study describes the first large screening of somatic mutations in SBA using next generation sequencing. The ERBB2 mutation was revealed to be one of the most frequent alterations in SBA with a distribution dependent on tumour location. In most cases ERBB2 mutation was identical (p.L755S). In clinical practice, this may suggest that more than 10% of the patients with SBA could be treated using an anti-ERBB2-targeted agent.     

Trends of cutaneous melanoma in The Netherlands: increasing incidence rates among all Breslow thickness categories and rising mortality rates since 1989

BackgroundIt has been debated that the epidemic of melanoma is largely due to overdiagnosis, since increases in incidence were mainly among thin melanomas and mortality rates remained stable. Our objective was to examine this controversy in The Netherlands.Patients and methodsInformation on newly diagnosed melanoma patients was obtained from The Netherlands Cancer Registry. European Standardized Rates and estimated annual percentage change were calculated for the period 1989–2008. Cohort-based, period-based and multivariate survival analyses were carried out.ResultsThe incidence rate of melanoma increased with 4.1% (95% confidence interval 3.6–4.5) annually. Incidence rates of both thin melanomas (≤1 mm) and thick melanomas (>4 mm) increased since 1989. Mortality rates increased mainly in older patients (<65 years). Ten-year relative survival of males improved significantly from 70% in 1989–1993 to 77% in 2004–2008 (P > 0.001) and for females the 10-year relative survival increased from 85% to 88% (P > 0.01). Recently diagnosed patients had a better prognosis even after adjusting for all known prognostic factors.ConclusionSince incidence of melanomas among all Breslow thickness categories increased as well as the mortality rates, the melanoma epidemic in The Netherlands seems to be real and not only due to overdiagnosis.     

Association of XRCC1 gene single nucleotide polymorphisms and susceptibility to pancreatic cancer in Chinese

The human X-ray repair cross-complementing group 1 gene (XRCC1) is an important candidate gene for affecting pancreatic cancer (PC) risk. The objective of this study was to detect whether the c.1471G?>?A and c.1686C?>?G polymorphisms of XRCC1 gene influence PC risk. The association of XRCC1 genetic variants with PC risk was analyzed in 328 PC patients and 350 controls by the polymerase chain reaction-restriction fragment length polymorphism and created restriction site-polymerase chain reaction method. Our data suggested that the genotypes and alleles from these two genetic variants were statistically associated with PC risk. For c.1471G?>?A, the AA genotype was associated with the decreased risk of developing PC compared to GG wild genotype (odds ratio (OR)?=?0.43, 95 % confidence intervals (CI) 0.26–0.70, chi-squared (χ ²)?=?11.91, P?=?0.001). For c.1686C?>?G, the risk of PC was significantly lower for GG genotype in comparing to CC wild genotype (OR?=?0.48, 95 % CI 0.29–0.81, χ ²?=?7.98, P?=?0.005). The A allele of c.1471G?>?A and G allele of c.1686C?>?G genetic variants could contribute to decrease the risk of PC (for c.1471G?>?A: A vs G, OR?=?0.65, 95 % CI 0.52–0.82, χ ²?=?13.71, P?<?0.001, for c.1686C?>?G: G vs C, OR?=?0.70, 95 % CI 0.55–0.88, χ ²?=?9.42, P?=?0.002). Our findings indicate that the c.1471G?>?A and c.1686C?>?G polymorphisms of XRCC1 gene are associated with PC risk in Chinese population.     

Overexpressed let-7a-3 is associated with poor outcome in acute myeloid leukemia

Dysregulation of microRNA let-7a-3 has been identified in several solid tumors and is associated with prognosis of patients. However, the pattern of let-7a-3 expression and the impact on prognosis has not yet been studied in acute myeloid leukemia (AML). The purpose of this study is to investigate the expression status of let-7a-3 and its clinical significance in AML patients using real-time quantitative PCR. Overexpression of let-7a-3 was identified in 25 of 102 (25%) de novo AML. There was no significant difference in age, blood parameters, FAB/WHO subtypes, karyotype risks and nine gene mutations (FLT3-ITD, NPM1, C-KIT, IDH1/IDH2, DNMT3A, C/EBPA and N/K-RAS) between patients with and without let-7a-3 overexpression (P > 0.05). The patients with let-7a-3 overexpression had similar rates of complete remission (CR) as those without let-7a-3 overexpression (50% vs. 56%, P = 0.693). Although the overall survival (OS) of AML patients with let-7a-3 overexpression (median 12 months,) was shorter than those without overexpression (median 25 months), the difference was not statistically significant (P = 0.228). However, among those 51 obtained CR, patients with let-7a-3 overexpression had significantly shorter OS than those without let-7a-3 overexpression (P = 0.029). The difference in relapse-free survival (RFS) was also significant between two groups (P = 0.005). These findings suggest that let-7a-3 overexpression is a common event and is associated with poor clinical outcome in AML.     

Two DNA repair gene polymorphisms on the risk of gastrointestinal cancers: a meta-analysis

PARP-1 and MGMT play an important role in the DNA repair system and therefore have been implicated in human carcinogenesis. However, the association between the most studied PARP-1 rs1136410: T?>?C and MGMT rs12917: C?>?T polymorphism and risk of gastrointestinal (GI) cancers was reported with inconclusive results. Accordingly, a meta-analysis of 23 published case–control studies was conducted to assess the strength of association using crude odds ratios (ORs) with 95 % confidence intervals (CIs). Overall, the C allele of PARP-1 rs1136410: T?>?C polymorphism was significantly associated with increased susceptibility of GI cancers (homozygote comparison: OR?=?1.43, 95 % CI 1.14–1.81; heterozygote comparison: OR?=?1.18, 95 % CI 1.07–1.29; dominant model: OR?=?1.23, 95 % CI 1.12–1.35; recessive model: OR?=?1.30, 95 % CI 1.04–1.62; allelic comparison: OR?=?1.19, 95 % CI 1.07–1.32). In the subgroup analysis, still obvious associations were found in the Asian population, gastric cancer, and high-quality studies. For MGMT rs12917: C?>?T polymorphism, no obvious associations were found for all genetic models overall. However, in the subgroup analysis, we found that the T allele was significantly associated with reduced colorectal cancer risk for heterozygote (OR?=?0.83, 95 % CI 0.70–0.97) and dominant model (OR?=?0.84, 95 % CI 0.72–0.98). In conclusion, this meta-analysis suggests that the PARP-1 rs1136410: T?>?C polymorphism is a susceptibility factor for GI cancers, but the variant allele of MGMT rs12917: C?>?T polymorphism appears to be a protective factor for colorectal cancer. Large-scale and well-designed case–control studies are necessary to validate the risk identified in the present meta-analysis.     

Direct Detection of the AR-E211 G > A Gene Polymorphism from Blood and Tissue Samples Without DNA Isolation

The pathogenesis of prostate cancer (CaP) involves alterations in a gene structure of the androgen receptor (AR). The single nucleotide polymorphism AR-E211 G?>?A localized in exon 1 of the AR gene (G1733A) was detected using direct polymerase chain reaction and restriction digestion (PCR-RFLP) method on blood and tissue samples without prior DNA isolation. We used blood samples of patients with a diagnosis of benign prostatic hyperplasia (BPH) or CaP. From monitored group of CaP patients were selected specimen in formalin-fixed paraffin-embedded tissue blocks with morphology of BPH and CaP. The main objective of our study was to develop a method based the direct PCR-RFLP analysis from blood and tissue without prior DNA isolation for faster genotyping analysis of a large number of samples. We found no statistically significant differences in allelic % of the AR-E211 G?>?A polymorphism between BPH and CaP patients (p?≤?0.8462). Genotyping of the AR-E211 G?>?A variant in blood was not identical with tumor tissue genotyping analysis. Significant agreement between blood and tissue AR-E211 G?>?A polymorphism only in non-tumor tissue focus was confirmed. Although we analyzed a limited number of the tissue samples, we suppose that a presence of the minor allele A may be associated with cancer transformation-induced changes of the modified AR gene.     

Association of Single Nucleotide Polymorphisms of the MDM4 Gene With the Susceptibility to Breast Cancer in a Southeast Iranian Population Sample

Introduction

The murine double minute 4 (MDM4) protein is a negative regulator of p53, and its upregulation has been observed in many tumor types. Previous literature suggested that genetic variations in the MDM4 gene are associated with risk of different cancers. The objective of the present study was to examine the effect of 3 common genetic variants of MDM4, rs4245739 A>C, rs11801299 G>A, and rs1380576 C>G, on the risk of breast cancer (BC) in a southeast Iranian population sample.