Polymorphisms of the NOS3 gene and risk of myocardial infarction in the Tunisian population

Controversial results regarding the association of eNOS gene (NOS3) polymorphisms with myocardial infarction (MI) have been reported. This study investigated the relationship of the −786T>C (rs2070744), 894G>T (rs1799983) and 4a4b polymorphisms of the NOS3 gene with the presence of MI in the Tunisian population. In addition, we also examined the association of NOS3 gene haplotypes with MI in Tunisian subjects.A total of 303 patients with MI and 225 controls were included in the study. The 894G>T and −786T>C single nucleotide polymorphisms were analyzed by PCR-RFLP, and 4a4b polymorphism just for PCR.There was significant linkage disequilibrium between the three NOS3 polymorphisms (p < 0.0001). The genotype distribution and allele frequency of NOS3 4a4b, but not −786T>C and 894G>T, polymorphism was significantly different between MI patients and controls. The univariate logistic regression analysis showed a significant association of the 4a4b polymorphism and MI according to co-dominant, dominant and recessive models (co-dominant model OR: 4.38, 95%CI: 1.24–15.41; p = 0.021, dominant model OR: 1.66, 95%CI: 1.14–2.42); p = 0.007, and recessive model OR: 3.85, 95%CI: 1.10–13.47; p = 0.035). The multivariate analysis, adjusted for traditional cardiovascular risk factors, revealed that the NOS3 4a4a genotype was an independent predisposing factor to MI, according to the models considered. In addition, a haplotype 7 (C-T-4a), (OR = 12.05, p = 0.010) was a risk factor of MI after controlling for classical risk factors.These finding suggest that the 4a4b polymorphism of the NOS3 gene was associated with MI in Tunisian patients.     

Diabetes,metformin use,and colorectal cancer survival in postmenopausal women

Background: Observational studies have associated metformin use with lower colorectal cancer (CRC) incidence but few studies have examined metformin's influence on CRC survival. We examined the relationships among metformin use, diabetes, and survival in postmenopausal women with CRC in the Women's Health Initiative (WHI) clinical trials and observational study. Methods: 2066 postmenopausal women with CRC were followed for a median of 4.1 years, with 589 deaths after CRC diagnosis from all causes and 414 deaths directly attributed to CRC. CRC-specific survival was compared among women with diabetes with metformin use (n = 84); women with diabetes with no metformin use (n = 128); and women without diabetes (n = 1854). Cox proportional hazard models were used to estimate associations among metformin use, diabetes and survival after CRC. Strategies to adjust for potential confounders included: multivariate adjustment with known predictors of colorectal cancer survival and construction of a propensity score for the likelihood of receiving metformin, with model stratification by propensity score quintile. Results: After adjusting for age and stage, CRC specific survival in women with diabetes with metformin use was not significantly different compared to that in women with diabetes with no metformin use (HR 0.75; 95% CI 0.40–1.38, p = 0.67) and to women without diabetes (HR 1.00; 95% CI 0.61–1.66, p = 0.99). Following propensity score adjustment, the HR for CRC-specific survival in women with diabetes with metformin use compared to non-users was 0.78 (95% CI 0.38–1.55, p = 0.47) and for overall survival was 0.86 (95% CI 0.49–1.52; p = 0.60). Conclusions: In postmenopausal women with CRC and DM, no statistically significant difference was seen in CRC specific survival in those who used metformin compared to non-users. Analyses in larger populations of colorectal cancer patients are warranted.     

The functional −94 insertion/deletion ATTG polymorphism in the promoter region of NFKB1 gene increases the risk of sporadic colorectal cancer

Objective: To investigate the allele and genotype frequencies of NFKB1 ?94 ins/del ATTG (rs28720239) polymorphism and to evaluate the association between the polymorphism and colorectal cancer (CRC) risk in Malaysian population. Methods: Genomic DNA was extracted from the peripheral blood samples of 474 study subjects, which consisted of 237 histopathologically confirmed CRC patients and an equal number of cancer-free controls. The NFKB1 ?94 ins/del ATTG (rs28720239) polymorphism was genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and confirmed by DNA sequencing. The association between the polymorphic genotypes and CRC risk was evaluated by deriving odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression analysis. Results: The frequencies of wildtype (del/del), heterozygous (del/ins) and variant (ins/ins) genotypes in CRC patients were 31.7%, 53.6% and 14.8%, respectively, while those in cancer-free controls were 35.0%, 58.2% and 6.8%, respectively. The frequency of the variant genotype was significantly higher in cases compared to controls (P < 0.01). Evaluation of the risk association of the polymorphic genotypes revealed that the variant genotype could contribute to a significantly increased risk of CRC (OR = 2.42, 95% CI = 1.24–4.73, P < 0.01). Conclusions: The variant allele of NFKB1 ?94 ins/del ATTG (rs28362491) polymorphism is associated with higher risk of sporadic CRC in Malaysian population.     

Germline HOXB13 p.Gly84Glu mutation and risk of colorectal cancer

Introduction: The HOXB13 pGly84Glu mutation has recently been associated with an increased risk of prostate cancer but the association of other cancer sites with this allele has not been assessed. Data has suggested that HOXB13 expression levels are decreased in colorectal cancer (CRC) cell lines indicating this gene may be involved in colorectal tumourigenesis. Methods: To evaluate a potential association of this mutation with CRC, we genotyped the mutation in 2695 CRC cases and 4593 controls from population-based registries in Canada and Australia. Results: The HOXB13 pGly84Glu mutation was more common in CRC cases than controls (0.48% vs. 0.17%, P = 0.02) indicating a significant association between the HOXB13 variant and CRC risk (OR = 2.8; 95%CI: 1.2–6.8). This association was attenuated but remained significant with the inclusion of previously published and publicly available genotype data. Pedigree analysis of cases and controls revealed that 7/21 HOXB13 mutation carriers had a family history of prostate cancer. Discussion: This report is the first to suggest a risk of CRC associated with mutations in the HOXB13 gene. These findings require further validation but may be of importance in the screening and genetic counseling of families known to carry the HOXB13 pGly84Glu mutation.     

Association between hypermethylation of DNA repetitive elements in white blood cell DNA and pancreatic cancer

Pancreatic cancer is a leading cause of cancer-related deaths worldwide. Methylation of DNA may influence risk or be a marker of early disease. The aim of this study was to measure the association between methylation of three DNA repetitive elements in white blood cell (WBC) DNA and pancreatic cancer.DNA from WBCs of pancreatic cancer cases (n = 559) and healthy unrelated controls (n = 603) were tested for methylation of the LINE-1, Alu and Sat2 DNA repetitive elements using MethyLight quantitative PCR assays. Odds ratios (ORs) and 95% confidence intervals (95%CI) between both continuous measures of percent of methylated sample compared to a reference (PMR) or quintiles of PMR and pancreatic cancer, adjusted for age, sex, smoking, BMI, alcohol and higher education, were estimated.The PMR for each of the three markers was higher in cases than in controls, although only LINE-1 was significantly associated with pancreatic cancer (OR per log unit = 1.37, 95%CI = 1.16–1.63). The marker methylation score for all three markers combined was significantly associated with pancreatic cancer (p-trend = 0.0006). There were no associations between measures of PMR and either presence of metastases, or timing of blood collection in relation to diagnosis, surgery, chemotherapy or death (all p > 0.1).We observed an association between methylation of LINE-1 in WBC DNA and risk of pancreatic cancer. Further studies are needed to confirm this association.     

Serum and urinary selenium levels in obese children: A cross-sectional study

ObjectiveTo determine serum and urinary selenium (Se) levels in children with and without obesity, and to assess if Se influences the risk of obesity.Subjects and methodsHigh-resolution-continuum source-atomic absorption spectrometry (HR-CS-AAS) was used to determine the content of Se in 80 children (age 6–17; 40 boys, 40 girls). Correlations between variables were tested with the use of Spearman's correlation coefficient. U Mann–Whitney test was applied to assess the difference of Se contents in samples. Measured metabolic risk factors (blood pressure, glucose level, triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and total cholesterol), age, gender, and BMI were correlated. Logistic regression models were fitted to identify predictors of obesity interacting with selenium content in serum and urine, separately.ResultsObese children, regardless of gender, had lower Se content. Se level in serum (p = 0.001, OR 0.74, 95%CI 0.62–0.88) and total cholesterol (p = 0.001, OR 1.19, 95%CI 1.08–1.31) were the independent factors significantly influencing the risk of obesity in children. Two separate models were observed for Se in urine: (i) Se level (p < 0. 0001, OR 0.70, 95%CI 0.58–0.84) and glucose level (p < 0.0001, OR 1.22, 95%CI 1.10–1.35), and (ii) Se level (p = 0.002, OR 0.60 95%CI 0.43–0.83) and total cholesterol level (p = 0.003, OR 1.16, 95%CI 1.05–1.28).ConclusionThe current study suggests a possible role of Se in obesity. Further research needs to be performed to check if obese children are an at-risk group for Se deficiency.     

An updated meta-analysis on the association of TGF-β1 gene promoter -509C/T polymorphism with colorectal cancer risk

AimPublished data on the association between transforming growth factor-β1 (TGF-β1) gene promoter-509C/T polymorphism and colorectal cancer (CRC) risk are inconsistent and inconclusive. To derive a more precise estimation of this association, a meta-analysis was carried out.MethodsMeta-analysis was performed to evaluate reported studies of the relationship between TGF-β1 gene promoter-509C/T polymorphism and colorectal cancer risk using fixed-effects model and random-effects model.ResultsWe observed an increased colorectal cancer risk among subjects carrying TGF-β1 gene promoter-509CC + CT genotype (odds ratio (OR) = 1.18%, 95% confidence interval (95% CI): 1.06–1.32) using 4440/6785 cases/controls in total population. We observed an increased risk of the TGF-β1 gene promoter -509CC, CT and CC + CT polymorphisms for colorectal cancer in population-based study (OR = 1.36, 95% CI: 1.19–1.56, OR = 1.18, 95% CI: 1.03–1.34 and OR = 1.26, 95% CI: 1.12–1.43, respectively) in stratified analysis. We observed an increased colorectal risk among CC and CC + CT carriers in European and American population (OR = 1.22, 95% CI: 1.04–1.43 and OR = 1.18, 95% CI: 1.02–1.38, respectively). We also observed an increased risk of colon cancer among subjects carrying CC + CT genotype (OR = 1.31, 95% CI: 1.05–1.63).ConclusionsThe present meta-analysis results suggest that TGF-β1 gene promoter -509C allele variant is a possible risk factor for developing colorectal cancer. Recommendations for further studies include pooling of individual data to verify results from the study and to facilitate evaluation of multigenic effects and detailed analysis of effect modification by environmental and lifestyle factors.     

DNA (cytosine-5)-methyltransferase 3B (DNMT 3B) polymorphism and risk of Down syndrome offspring

Down syndrome (DS) is the most common form of human genetic mental retardation. Several polymorphisms in genes coding folic acid cycle enzymes have been associated to the risk of bearing a DS child; however, the results are controversial. S-adenosyl-l-methionine (SAM) is an important intermediate of folic acid pathway and acts as methyl donor and substrate for DNA (cytosine-5)-methyltransferase 3B (DNMT3B – EC 2.1.1.37) de novo methylation processes during embryogenesis. Recent studies suggest that a functional polymorphism of DNMT 3B in maternal genotype may be associated with a decreased risk of having a DS child. We herein investigate the association of this polymorphism with the occurrence of DS in a Brazilian population. We have genotyped 111 mothers of DS infants (MDS) and 212 control mothers (CM) through PCR-RFLP. The observed genotypic frequencies were CC = 0.22; CT = 0.49 and TT = 0.29 in CM, and CC = 0.30; CT = 0.52 and TT = 0.18 in MDS. Allelic frequencies were C = 0.47 and T = 0.53 in CM and C = 0.56 and T = 0.44 in MDS. No deviation of HWE was observed, and both DNMT 3B rs2424913 genotype (χ2 = 4.53; DF = 1; P = 0.03) and allelic (χ2 = 4.90; DF = 1; P = 0.03) frequencies show significant differences between MDS and CM. The presence of the mutant DNMT 3B T allele decreases 30% the risk of bearing a DS child (OR = 0.69; 95% CI: 0.50–0.96; P = 0.03), and the risk is diminished up to 45% in association with the homozygous genotype (OR = 0.54; 95% CI: 0.31–0.96; P = 0.04). Our results suggest that women harboring the single nucleotide polymorphism DNMT 3B rs2424913 have a decreased risk of a DS pregnancy, and further studies are necessary to confirm this protective effect.     

Association between periodontitis and common variants in the promoter of the interleukin-6 gene

We recently reported an association between interleukin-6 (IL6) polymorphisms (SNPs) and haplotypes and aggressive periodontitis (AgP). The aim of this study was to investigate this association in a larger cohort of subjects, affected by either aggressive or chronic periodontitis. Five IL6 SNPs were analyzed in 765 subjects (167 generalized aggressive periodontitis, 57 localized aggressive, 310 chronic periodontitis and 231 periodontally healthy). Among Caucasians (n = 454) there were moderate associations for ?1363T allele (p = 0.011) and for ?174GG and ?1363GG genotypes with diagnosis of periodontitis (respectively, p = 0.044, OR = 1.6, 95% CI = 1.0–2.4, and p = 0.017, OR = 1.8, 95% CI = 1.1–2.8, adjusted for age, gender and smoking). Haplotypes containing the ?174G>C, ?1363G>T and ?1480C>G polymorphisms were associated with diagnosis of periodontitis (p = 0.02). Subgroup analysis by disease phenotype showed associations for the localized AgP (LAgP) group and ?1480C>G and ?6106A>T SNPs (p = 0.007 and 0.010, respectively). Among Caucasians the genotypes IL6 ?1480 CC and ?6106 TT increased the adjusted OR for LAgP (OR = 3.09 and 2.27, respectively). This study supports the hypothesis that IL6 polymorphisms and haplotypes are moderately associated with periodontitis, possibly acting through influencing tissue levels of IL6. This association is stronger for LAgP than for other periodontal disease phenotypes.     

CYP1A2 genetic polymorphisms and adenocarcinoma lung cancer risk in the Tunisian population

AimsIn this study, the effects of four single nucleotide polymorphisms (SNPs), ? 3860G > A, ? 2467delT, ? 739T > G and ? 163C > A, of CYP1A2 gene on lung cancer were evaluated in Tunisian population.Main methodsFour polymorphisms of CYP1A2 gene were analysed in 109 healthy smokers and in 101 lung cancer cases, including 63 with squamous cell carcinoma (SCC) and 41 with adenocarcinoma (AD). The genotyping for the SNPs ? 3860 G > A, ? 2467delT, ? 739T > G and ? 163C > A was performed by polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis.Key findingsThe results showed that smokers with CYP1A2 gene polymorphisms were associated with an increased risk for the development of lung AD. There was however no significant increased risk of developing lung SCC in smokers having CYP1A2 gene polymorphisms. An increased risk of developing AD was observed in smokers who are carriers of at least one copy of ? 3680A or ? 739G giving a significant odds ratio (OR) of 6.02 (CI = 2.91–12.9) and 3.01 (CI = 1.54–5.98), respectively.SignificanceThese genotyping data are consistent with the hypothesis that tobacco-specific-N-nitrosamines (TSN) such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are major contributors to the development of lung AD and that CYP1A2 gene product plays an important role in the metabolic activation of NNK. This study suggests that SNPs of CYP1A2 could be considered as promising biomarkers in the aetiology of lung AD in smokers.     

Meta-analysis of the clinicopathological characteristics and peri-operative outcomes of colorectal cancer in obese patients

BackgroundThe effect of obesity on the clinicopathological characteristics of colorectal cancer (CRC) has not been clearly characterized. This meta-analysis assesses the pathological and perioperative outcomes of obese patients undergoing surgical resection for CRC.MethodsMeta-analysis was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Databases were searched for studies reporting outcomes for obese and non-obese patients undergoing primary CRC resection, based on body-mass index measurement. Results were reported as mean differences or pooled odds ratios (OR) with 95% confidence intervals (95% CI).ResultsA total of 2183 citations were reviewed; 29 studies comprising 56,293 patients were ultimately included in the analysis, with an obesity rate of 19.3%. Obese patients with colorectal cancer were more often female (OR 1.2, 95% CI 1.1–1.2, p < 0.001) but there was no difference in the proportion of rectal cancers, T4 tumours, tumour differentiation or margin positivity. Obese patients were significantly more likely to have lymph node metastases (OR 1.2, 95% CI 1.1–1.2, p < 0.001), have a lower nodal yield, were associated with a longer duration of surgery, more blood loss and conversions to open surgery (OR 2.6, 95% CI 1.6–4.0, p < 0.001) but with no difference in length of stay or post-operative mortality.ConclusionThis meta-analysis demonstrates that obese patients undergoing resection for CRC are more likely to have node positive disease, longer surgery and higher failure rates of minimally invasive approaches. The challenges of colorectal cancer resection in obese patients are emphasized.     

HapMap-based study identifies risk sub-region on chromosome 19q13.3 in relation to lung cancer among Chinese

Background: Chromosome 19q13.3 has been identified as one of the regions that associate with cancer risk in previous studies. Methods: We systematically examined the 70.772 kb region comprising four genes on chromosome 19q13.3 among Chinese using the haplotype-tagging SNP (htSNP) approach and the HapMap platform. The study involved 339 lung cancer cases and 358 non-cancer controls. Two htSNPs (rs1046282 and rs735482) captured most of the common haplotypes of CD3EA and the combined effects of sixteen htSNPs provided high coverage of common haplotypes of ERCC2, PPP1R13L, CD3EAP and ERCC1. Results: Both carriers of variant CC genotype [adjusted OR (95% CI) = 1.28 (1.02–1.60), P = 0.04] and variant C-allele among >20 years’ smokers [OR (95% CI) = 2.13 (1.24–3.67), P = 0.006] for CD3EAP rs735482 were at increased risk of lung cancer. Four haplotype blocks of strong linkage disequilibrium were identified. The haplotype ERCC2 rs3916874^G and rs238415^C [OR (95% CI) = 1.26 (1.02–1.57), P = 0.03] in block 1 and the haplotype PPP1R13L rs4803817^A, CD3EAP rs1046282^T, rs735482^C, ERCC1 rs3212980^A, rs3212964^G [OR (95% CI) = 3.56 (1.55–8.18), P = 0.005] in block 3 were associated with lung cancer risk. MDR (multifactor dimensionality reduction) analysis demonstrated the best significant model of two-attributes containing smoking duration and rs2298881 in ERCC1 (P = 0.004–0.005) and suggested that the effects of high-order interactions among smoking duration and ERCC2, PPP1R13, ERCC1 htSNPs could modulate lung cancer risk. Conclusions: HapMap-based study of 19q13.3 identified that genetic variation of CD3EAP and two loci were associated with lung cancer risk and interaction of smoking duration and genetic variants was the strongest predictor of lung cancer risk in a Chinese population.     

Time to diagnosis and stage of symptomatic colorectal cancer determined by three different sources of information: A population based retrospective study

BackgroundSurvival rates from colorectal cancer (CRC) are highly variable in Europe. This variability could potentially be explained by differences in healthcare system delays in diagnosis. However, even when such delays are reduced, the relationship of the diagnostic interval (time from presentation with symptoms to diagnosis) with outcome is uncertain.MethodsA total of 795 patients with CRC from 5 regions of Spain were retrospectively examined in this population-based multicenter study. Consecutive incident cases of CRC were identified from pathology services. The total diagnostic interval (TDI) was defined as the time from the first presentation with symptoms to diagnosis based on 3 different sources of information: (i) patient-recorded data (PR-TDI) by interview, (ii) hospital-recorded data (HR-TDI), and (iii) general practitioner-recorded data (GPR-TDI). Concordance correlation coefficients (CCCs) were used to estimate the agreement of 3 different TDIs. The TDIs of patients with different stages of CRC were also compared using the Kruskal-Wallis test.ResultsThe median TDI was 131 days based on patient interview data, 91 days based on HR data, and 111 days based on GPR data. Overall, the agreement of these TDIs was poor (CCC_PRvsHR = 0.399, CCC_PRvsGPR = 0.518, CCC_HRvsGPR = 0.383). Univariate analysis indicated that the TDI was greater in those with less advanced CRC for all 3 methods of calculation, but this association was only statistically significant for the HR-TDI (p = 0.021).ConclusionThere is no evidence that patients with more advanced CRC have longer TDIs. In fact, we found an inverse relationship between the TDI and CRC stage, an example of the “waiting time paradox”. This association may likely be due to the presence of unmeasured confounders as the stage when symptoms appear or the tumour aggressiveness.     

Trends and inequities in colorectal cancer screening participation in Ontario,Canada, 2005–2011

Background: Participation in screening tests for colorectal cancer (CRC) is generally low in Ontario, Canada. In addition, inequities in participation exist including lower participation among low-income individuals, males and individuals living in rural areas. In April 2008, Colon Cancer Check (CCC) program, the province-wide CRC screening program, was launched in Ontario. This study describes the trends and inequities in CRC screening participation three years before and three years after the CCC, and assesses the effect of the program on CRC screening participation, overall and among certain population groups. Methods: We used administrative data to identify cohorts of individuals eligible for CRC screening in fiscal years 2005–2011. We calculated the age-standardized percent of Fecal Occult Blood Test (FOBT) participation, large bowel endoscopy participation, and being ‘up-to-date’ with CRC screening tests. Results: From 2005 to 2011, FOBT participation increased from 7.6% to 14.8%, large bowel endoscopy participation from 3.4% to 5.7%, and ‘up-to-date’ with CRC screening from 27.2% to 41.3%. Before the launch of the CCC program, the quarterly increase in FOBT participation was 0.07% (p = 0.19), increased immediately after the launch (1.8%, p < 0.01), followed by a decline (?0.08%, p = 0.08), returning to its pre-program increase rate. We noted a significant decrease in FOBT participation every summer (?0.44%, p < 0.01). The CCC program had minimal effect on large bowel endoscopy participation. Before the launch of the CCC program, the quarterly increase in ‘up-to-date’ with CRC screening was 0.9% (p < 0.01), increased immediately after the launch (2.5%, p = 0.05), followed by a modest decline thereafter (?0.59%, p < 0.02). From 2005 to 2011, recent residents living in low-income neighborhoods were consistently and significantly less likely to have a FOBT and be ‘up-to-date’ with CRC screening than long-term residents living in high-income neighborhoods (2.9–4.5%; 14.7–17.3% respectively). Pre-CCC inequities in CRC participation persisted after the launch of the program. Conclusion: CRC testing was increasing in Ontario from 2005. An immediate increase in CRC testing, FOBT in particular, occurred after the launch of the CCC program, followed by a return to its pre-CCC increase rate thereafter. Future efforts are needed to improve screening participation and address inequities.     

Patterns of metachronous metastases after curative treatment of colorectal cancer

BackgroundThis study aimed to provide information on timing, anatomical location, and predictors for metachronous metastases of colorectal cancer based on a large consecutive series of non-selected patients.MethodsAll patients operated on with curative intent for colorectal cancer (T_anyN_anyM₀) between 2003 and 2008 in the Dutch Eindhoven Cancer Registry were included (N = 5671). By means of active follow-up by the Cancer Registry staff within ten hospitals, data on development of metastatic disease were collected. Median follow-up was 5.0 years.ResultsOf the 5671 colorectal cancer patients, 1042 (18%) were diagnosed with metachronous metastases. Most common affected sites were the liver (60%), lungs (39%), extra-regional lymph nodes (22%), and peritoneum (19%). 86% of all metastases was diagnosed within three years and the median time to diagnosis was 17 months (interquartile range 10–29 months). Male gender (HR = 1.2, 95%CI 1.03–1.32), an advanced primary T-stage (T4 vs. T3 HR = 1.6, 95%CI 1.32–1.90) and N-stage (N1 vs. N0 HR = 2.8, 95%CI 2.42–3.30 and N2 vs. N0 HR = 4.5, 95%CI 3.72–5.42), high-grade tumour differentiation (HR = 1.4, 95%CI 1.17–1.62), and a positive (HR = 2.1, 95%CI 1.68–2.71) and unknown (HR = 1.7, 95%CI 1.34–2.22) resection margin were predictors for metachronous metastases.ConclusionsDifferent patterns of metastatic spread were observed for colon and rectal cancer patients and differences in time to diagnosis were found. Knowledge on these patterns and predictors for metachronous metastases may enhance tailor-made follow-up schemes leading to earlier detection of metastasized disease and increased curative treatment options.     

Breast cancer detection risk in screening mammography after a false-positive result

Background: False-positives are a major concern in breast cancer screening. However, false-positives have been little evaluated as a prognostic factor for cancer detection. Our aim was to evaluate the association of false-positive results with the cancer detection risk in subsequent screening participations over a 17-year period. Methods: This is a retrospective cohort study of 762,506 women aged 45–69 years, with at least two screening participations, who underwent 2,594,146 screening mammograms from 1990 to 2006. Multilevel discrete-time hazard models were used to estimate the adjusted odds ratios (OR) of breast cancer detection in subsequent screening participations in women with false-positive results. Results: False-positives involving a fine-needle aspiration cytology or a biopsy had a higher cancer detection risk than those involving additional imaging procedures alone (OR = 2.69; 95%CI: 2.28–3.16 and OR = 1.81; 95%CI: 1.70–1.94, respectively). The risk of cancer detection increased substantially if women with cytology or biopsy had a familial history of breast cancer (OR = 4.64; 95%CI: 3.23–6.66). Other factors associated with an increased cancer detection risk were age 65–69 years (OR = 1.84; 95%CI: 1.67–2.03), non-attendance at the previous screening invitation (OR = 1.26; 95%CI: 1.11–1.43), and having undergone a previous benign biopsy outside the screening program (OR = 1.24; 95%CI: 1.13–1.35). Conclusion: Women with a false-positive test have an increased risk of cancer detection in subsequent screening participations, especially those with a false-positive result involving cytology or biopsy. Understanding the factors behind this association could provide valuable information to increase the effectiveness of breast cancer screening.     

Concentration of vascular endothelial growth factor in patients with acute coronary syndrome

Vascular endothelial growth factor (VEGF) is a regulator of vascular formation in physiological and pathological conditions. The aim of our study was to evaluate the value of VEGF as a surrogate marker of myocardial injury in acute ischemic conditions.Materials and methodsIn 104 consecutive patients with acute coronary syndrome (ACS) with and without ST segment elevation (STEMI and NSTEMI) the plasma and serum human VEGF (hVEGF) concentration was measured two times i.e. immediately after admission due to ACS and 24 h later. According to ECG findings and coronary angiography results, patients were divided into three groups. Group A represented major myocardial injury due to ST-segment elevation in precordial leads and/or in I and aVL leads and with left anterior descending (LAD) artery responsible for STEMI symptoms or additionally with significant atherosclerotic lesions (lumen vessel narrowed >50%) in other than LAD coronary arteries. Group B (medium myocardial injury) consisted of patients with ST-segment elevation in II, III and aVF leads and/or ST-segment depression in V2-V3 leads with one-vessel disease and the culprit artery was not LAD. Group C included patients with changes in ECG other than ST-segment elevation independently of the site of atherosclerotic lesions in coronary arteries.ResultsIn all 104 patients with ACS the highest values of serum hVEGF were observed in second measurement (357.9 ± 346 pg/ml, p < 0.01). Although in the first measurement, plasma and serum hVEGF concentration did not differentiate groups, the difference between deltas for serum hVEGF was observed (p < 0.05). Increased number of neutrophils in the first measurement increased the OR of the high serum hVEGF concentration in the first measurement (OR = 1.155; 95%CI: 1.011; 1.32) (p < 0.05). The number of neutrophils in the second measurement also revealed significant relationship with high serum hVEGF in the first assessment (OR = 1.318, 95%CI: 1.097; 1.583) (p < 0.01). Increased values of triglycerides (exceeding the upper limit) were connected with decreased OR of high serum hVEGF concentrations in the first measurement (OR = 0.152, 95%CI: 0.033; 0.695, p < 0.05).ConclusionsIn acute coronary syndrome, serum VEGF concentrations are elevated and can serve as a surrogate marker of myocardial injury. The elevated number of neutrophils increases odds ratio of high VEGF concentrations in ACS. In patients with high concentrations of triglycerides, odds ratio of low level of hVEGF is expected.     

The relationship between ethnicity,social deprivation and late presentation of colorectal cancer

IntroductionTumour staging at time of presentation is an important factor in determining survival in colorectal cancer. The aim of this paper is to investigate the relationship between ethnicity and deprivation in late (Stage IV) presentation of colorectal cancer.MethodsData from the Thames Cancer Registry comprising 77,057 colorectal cancer patients between the years 2000 and 2012 were analysed.ResultsA total of 17,348 patients were identified with complete data, of which 53.9% were male. Patients from a Black Afro/Caribbean background were diagnosed with CRC at a much younger age than the White British group (median age 67 compared with 72, p < 0.001). In multiple regression, ethnicity, deprivation and age were positive predictors of presenting with advanced tumour stage at time of diagnosis. Black patients were more likely to present with Stage IV tumours than white patients (OR 1.37, 95% CI 1.18–1.59, p < 0.001). Social deprivation was also a predictor of Stage IV cancer presentation, with the most deprived group (Quintile 5) 1.26 times more likely to be diagnosed with Stage IV cancer compared with the most affluent group (CI 1.13–1.40, p < 0.001). Sub-group analyses demonstrated that Black & Affluent patients were still at greater risk of Stage IV CRC than their White & Affluent counterparts (OR 1.24, 95% CI 1.11–1.45, p = 0.023). Patients with rectal cancer were less likely to present with Stage IV CRC (OR 0.66, 95% CI 0.61–0.71, p < 0.001).ConclusionRacial and age related disparities exist in tumour presentation in the United Kingdom. Patients from black and socially deprived backgrounds as well as the elderly are more likely to present with advanced tumours at time of diagnosis.     

10-Year risk of colorectal cancer: Development and validation of a prediction model in middle-aged Japanese men

Background: To estimate an individual's probability of developing colorectal cancer (CRC) may aid health professionals and individuals in improving lifestyle behaviors or deciding the screening regimens. As fewer studies on cancer risk prediction were seen so far, we initially developed an assessment tool with synthesizing key information from a variety of CRC risk factors through a large population-based cohort study. Method: The prediction model was derived from 28,115 men in the Japan Public Health Center-based (JPHC) Prospective Study Cohort II (follow-up: 1993–2005), with risk factors selected by Cox proportion hazard regression. 18,256 men in the JPHC Study Cohort I (follow-up: 1995–2005) were used to evaluate the model's performance. Results: 543 and 398 CRCs were diagnosed during the follow-up period in Cohorts II and I, respectively. The prediction model, including age, BMI, alcohol consumption, smoking status, and the daily physical activity level, showed modest discrimination ability for CRC (C = 0.70; 95% confidential interval, 0.68–0.72) in Cohort II and well calibrated in Cohort I (Hosmer–Lemeshow χ² = 14.2, P = 0.08). Conclusion: The 10-year CRC risk prediction model may be used to estimate CRC risk in Japanese men. It may also play a role in the promotion of CRC prevention strategies.