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1.  Predictive factors of proximal advanced neoplasia in the large bowel 
Archives of Medical Science : AMS  2014;10(3):484-489.
The aim of the study was to evaluate the impact of sex, age, family history and distal findings on the risk of proximal advanced neoplasia (cancer or advanced adenoma) in the large bowel.
Material and methods
Records for 10 111 asymptomatic participants of the Colonoscopy Screening Program (CSP), recruited from the Warsaw region between 2000 and 2004, were analyzed. A multivariate logistic regression model was used to estimate the impact of sex, age, family history and most advanced distal lesions on the occurrence of proximal advanced neoplasia. To enhance comparability of the study two definitions of the proximal colon were applied – either the splenic flexure (1st) or the bend between the descending and sigmoid colon (2nd definition) represented the boundary.
One hundred and thirty-three (1st) and 167 patients (2nd definition) were found to have at least one advanced neoplastic lesion in the proximal part, respectively. Eleven and 14 patients were found to have carcinoma, while in 130 and 163 patients at least one proximal advanced adenoma appeared. Men were at twice as high risk of having advanced neoplasia in the proximal colon than women (OR = 1.94, 95% CI: 1.31–2.87, p = 0.001 or OR = 1.69, 95% CI: 1.20–2.40, p = 0.003, respectively). The presence of distal advanced neoplastic lesions was associated with 3.5 times higher risk of proximal advanced neoplasia (OR = 3.58, 95% CI: 2.00–6.43, p < 0.0001 or OR = 3.41, 95% CI: 1.95–5.96, p < 0.0001), respectively.
The results may confirm some limitation of flexible sigmoidoscopy in the screening settings in comparison with colonoscopy, at least in men and people with distal advanced neoplasia.
PMCID: PMC4107244  PMID: 25097578
colonoscopy; colorectal cancer; neoplasia; flexible sigmoidoscopy; screening
2.  Modulation of Age- and Cancer-Associated DNA Methylation Change in the Healthy Colon by Aspirin and Lifestyle 
Aberrant DNA methylation in gene promoters is associated with aging and cancer, but the circumstances determining methylation change are unknown. We investigated the impact of lifestyle modulators of colorectal cancer (CRC) risk on the stability of gene promoter methylation in the colonic mucosa.
We measured genome-wide promoter CpG methylation in normal colon biopsies (n = 1092) from a female screening cohort, investigated the interaction of lifestyle factors with age-dependent increase in methylation with log-linear multivariable regression, and related their modifying effect to hypermethylation in CRC. All statistical tests were two-sided.
Of 20025 promoter-associated CpGs analyzed, 1713 showed statistically significant age-dependent methylation gains. Fewer CpGs acquired methylation in users of aspirin (≥2 years) and hormonal replacement therapy (HRT age ≥50 years) compared with nonusers (43 vs 1355; 1 vs1377, respectively), whereas more CpGs were affected in smokers (≥20 years) and individuals with a body mass index (BMI) of 25kg/m2 and greater compared with control groups (180 vs 39; 554 vs 144, respectively). Fifty percent of the CpGs showing age-dependent methylation were found hypermethylated in CRC (odds ratio [OR] = 20; 95% confidence interval [CI] = 18 to 23; P < 2×10–16). These loci gained methylation with a higher median rate compared with age-only methylated sites (P = 2×10–76) and were enriched for polycomb regions (OR = 3.67). Importantly, aspirin (P < .001) and HRT use (P < .001) reduced the methylation rate at these cancer-related genes, whereas smoking (P < .001) and high BMI (P = .004) increased it.
Lifestyle, including aspirin use, modulates age-associated DNA methylation change in the colonic epithelium and thereby impacts the evolution of cancer methylomes.
PMCID: PMC4112799  PMID: 24973978
4.  Small bowel tumors detected and missed during capsule endoscopy: Single center experience 
AIM: To characterize small bowel (SB) tumors detected by capsule endoscopy (CE), and identify missed tumors.
METHODS: The study included 145 consecutive patients in whom 150 CEs were performed. Following CE, the medical records of the study population were reviewed. Results of double- or single-balloon enteroscopy performed after CE and the results of surgery in all patients operated on were retrieved. The patients were contacted through telephone interviews or postal mail. In addition, the national cancer registry and the polish clinical gastrointestinal stromal tumor (GIST) Registry were searched to identify missed neoplasms.
RESULTS: Indications for CE included overt and occult obscure gastrointestinal bleeding (n = 81, 53.7%), anemia (n = 19, 12.7%), malabsorption (n = 18, 12%), abnormal CB follow through (n = 9, 6%), abdominal pain (n = 7, 5%), celiac disease (n = 5, 3%), neuroendocrine tumor (n = 3, 2%), Crohn’s disease (n = 2, < 2%), Peutz-Jeghers syndrome (n = 2, < 2%), other polyposes (n = 2, < 2%), and diarrhea (n = 2, < 2%). The capsule reached the colon in 115 (76.6%) examinations. In 150 investigations, CE identified 15 SB tumors (10%), 14 of which were operated on or treated endoscopically. Malignancies included metastatic melanoma (n = 1), adenocarcinoma (n = 2), and GIST (n = 3). Benign neoplasms included dysplastic Peutz-Jeghers polyps (n = 4). Non-neoplastic masses included venous malformation (n = 1), inflammatory tumors (n = 2), and a mass of unknown histology (n = 1). During the follow-up period, three additional SB tumors were found (2 GISTs and one mesenteric tumor of undefined nature). The National Cancer Registry and Polish Clinical GIST Registry revealed no additional SB neoplasms in the post-examination period (follow-up: range 4.2-102.5 mo, median 39 mo). The sensitivity of CE for tumor detection was 83.3%, and the negative predictive value was 97.6%. The specificity and positive predictive value were both 100%.
CONCLUSION: Neoplasms may be missed by CE, especially in the proximal SB. In overt obscure gastrointestinal bleeding, complementary endoscopic and/or radiologic diagnostic tests are indicated.
PMCID: PMC3870557  PMID: 24379629
Capsule endoscopy; Small bowel tumor; Tumor miss rate; Gastrointestinal bleeding; Gastrointestinal stromal tumor
6.  Association of genetic variation in the NR1H4 gene, encoding the nuclear bile acid receptor FXR, with inflammatory bowel disease 
BMC Research Notes  2012;5:461.
Pathogenesis of inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn’s disease (CD), involves interaction between environmental factors and inappropriate immune responses in the intestine of genetically predisposed individuals. Bile acids and their nuclear receptor, FXR, regulate inflammatory responses and barrier function in the intestinal tract.
We studied the association of five variants (rs3863377, rs7138843, rs56163822, rs35724, rs10860603) of the NR1H4 gene encoding FXR with IBD. 1138 individuals (591 non-IBD, 203 UC, 344 CD) were genotyped for five NR1H4 genetic variants with TaqMan SNP Genotyping Assays.
We observed that the NR1H4 SNP rs3863377 is significantly less frequent in IBD cases than in non-IBD controls (allele frequencies: P = 0.004; wild-type vs. SNP carrier genotype frequencies: P = 0.008), whereas the variant rs56163822 is less prevalent in non-IBD controls (allele frequencies: P = 0.027; wild-type vs. SNP carrier genotype frequencies: P = 0.035). The global haplotype distribution between IBD and control patients was significantly different (P = 0.003). This also held true for the comparison between non-IBD and UC groups (P = 0.004), but not for the comparison between non-IBD and CD groups (P = 0.079).
We show that genetic variation in FXR is associated with IBD, further emphasizing the link between bile acid signaling and intestinal inflammation.
PMCID: PMC3517390  PMID: 22929053
Bile acid homeostasis; Crohn’s disease; Farnesoid X receptor; Inflammatory bowel disease; Single nucleotide polymorphisms; Ulcerative colitis
7.  Pooled Sample-Based GWAS: A Cost-Effective Alternative for Identifying Colorectal and Prostate Cancer Risk Variants in the Polish Population 
PLoS ONE  2012;7(4):e35307.
Prostate cancer (PCa) and colorectal cancer (CRC) are the most commonly diagnosed cancers and cancer-related causes of death in Poland. To date, numerous single nucleotide polymorphisms (SNPs) associated with susceptibility to both cancer types have been identified, but their effect on disease risk may differ among populations.
To identify new SNPs associated with PCa and CRC in the Polish population, a genome-wide association study (GWAS) was performed using DNA sample pools on Affymetrix Genome-Wide Human SNP 6.0 arrays. A total of 135 PCa patients and 270 healthy men (PCa sub-study) and 525 patients with adenoma (AD), 630 patients with CRC and 690 controls (AD/CRC sub-study) were included in the analysis. Allele frequency distributions were compared with t-tests and χ2-tests. Only those significantly associated SNPs with a proxy SNP (p<0.001; distance of 100 kb; r2>0.7) were selected. GWAS marker selection was conducted using PLINK. The study was replicated using extended cohorts of patients and controls. The association with previously reported PCa and CRC susceptibility variants was also examined. Individual patients were genotyped using TaqMan SNP Genotyping Assays.
The GWAS selected six and 24 new candidate SNPs associated with PCa and CRC susceptibility, respectively. In the replication study, 17 of these associations were confirmed as significant in additive model of inheritance. Seven of them remained significant after correction for multiple hypothesis testing. Additionally, 17 previously reported risk variants have been identified, five of which remained significant after correction.
Pooled-DNA GWAS enabled the identification of new susceptibility loci for CRC in the Polish population. Previously reported CRC and PCa predisposition variants were also identified, validating the global nature of their associations. Further independent replication studies are required to confirm significance of the newly uncovered candidate susceptibility loci.
PMCID: PMC3331859  PMID: 22532847
8.  Reliability and validity of the Gastrointestinal Symptom Rating Scale (GSRS) and Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaire in dyspepsia: A six-country study 
Symptoms of dyspepsia significantly disrupt patients' lives and reliable methods of assessing symptom status are important for patient management. The aim of the current study was to document the psychometric characteristics of the Gastrointestinal Symptom Rating Scale (GSRS) and the Quality of Life in Reflux and Dyspepsia questionnaire (QOLRAD) in Afrikaans, German, Hungarian, Italian, Polish and Spanish patients with dyspepsia.
853 patients with symptoms of dyspepsia completed the GSRS, the QOLRAD, the 36-item Short-Form Health Survey (SF-36) and the Hospital Anxiety and Depression scale.
The internal consistency reliability of the GSRS was 0.43–0.87 and of the QOLRAD 0.79–0.95. Test-retest reliability of the GSRS was 0.36–0.75 and of the QOLRAD 0.41–0.82. GSRS Abdominal pain domain correlated significantly with all QOLRAD domains in most language versions, and with SF-36 Bodily pain in all versions. QOLRAD domains correlated significantly with the majority of SF-36 domains in most versions. Both questionnaires were able to differentiate between patients whose health status differed according to symptom frequency and severity.
The psychometric characteristics of the different language versions of the GSRS and QOLRAD were found to be good, with acceptable reliability and validity. The GSRS and QOLRAD were found to be useful for evaluating dyspeptic symptoms and their impact on patients' daily lives in multinational clinical trials.
PMCID: PMC2276197  PMID: 18237386
9.  A score to estimate the likelihood of detecting advanced colorectal neoplasia at colonoscopy 
Gut  2014;63(7):1112-1119.
This study aimed to develop and validate a model to estimate the likelihood of detecting advanced colorectal neoplasia in Caucasian patients.
We performed a cross-sectional analysis of database records for 40-year-old to 66-year-old patients who entered a national primary colonoscopy-based screening programme for colorectal cancer in 73 centres in Poland in the year 2007. We used multivariate logistic regression to investigate the associations between clinical variables and the presence of advanced neoplasia in a randomly selected test set, and confirmed the associations in a validation set. We used model coefficients to develop a risk score for detection of advanced colorectal neoplasia.
Advanced colorectal neoplasia was detected in 2544 of the 35 918 included participants (7.1%). In the test set, a logistic-regression model showed that independent risk factors for advanced colorectal neoplasia were: age, sex, family history of colorectal cancer, cigarette smoking (p<0.001 for these four factors), and Body Mass Index (p=0.033). In the validation set, the model was well calibrated (ratio of expected to observed risk of advanced neoplasia: 1.00 (95% CI 0.95 to 1.06)) and had moderate discriminatory power (c-statistic 0.62). We developed a score that estimated the likelihood of detecting advanced neoplasia in the validation set, from 1.32% for patients scoring 0, to 19.12% for patients scoring 7–8.
Developed and internally validated score consisting of simple clinical factors successfully estimates the likelihood of detecting advanced colorectal neoplasia in asymptomatic Caucasian patients. Once externally validated, it may be useful for counselling or designing primary prevention studies.
PMCID: PMC4078748  PMID: 24385598

Results 1-9 (9)