Cyclooxygenase-2, multidrug resistance 1, and breast cancer resistance protein gene polymorphisms and inflammatory bowel disease in the Danish population

Østergaard, Mette; Ernst, Anja; Labouriau, Rodrigo; Dagiliene, Enrika; Krarup, Henrik; Christensen, Mariann; Thorsgaard, Niels; Jacobsen, Bent Ascanius; Tage-Jensen, U; Overvad, Kim; Autrup, Herman; Andersen, Vibeke

doi:10.1080/00365520802400826

Cited by 32 publications

(33 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, our control group data on the COX-2 -765 genotype were in good agreement with other European control data recently reported from Denmark, being 73.2%, 24.8% and 2.0% for -765 GG, GC and CC genotypes, respectively [16] . In addition, the COX-2 polymorphism data in our patients are very similar to the recently reported COX-2 -765 and -1195 genotype distributions in Dutch esophageal adenocarcinoma patients by Moons et al [17] , except for the -1195 GG genotype, which was present in 8.0% of our patients vs only 2.0% in the patients in the study by Moons et al [17] .…”

Section: Discussionsupporting

confidence: 80%

Cyclooxygenase-2 polymorphisms and the risk of esophageal adeno- or squamous cell carcinoma

Kristinsson¹,

Westerveld²,

Morsche³

et al. 2009

WJG

View full text Add to dashboard Cite

AIM:To determine whether -1195 A →G and/or -765 G →C polymorphisms in Cyclooxygenase-2 (COX-2 ) may have a risk modifying effect on the development of esophageal carcinoma in a Dutch Caucasian population. METHODS:Two study groups were recruited, 252 patients with esophageal carcinoma and 240 healthy controls, matched for race, age, gender and recruiting area. DNA was isolated from whole blood and used for genotyping. PCR products were digested with restriction enzymes and products were analyzed by agarose gel electrophoresis. Odds ratios (OR) and 95% confidence intervals (CI) were estimated. RESULTS: T h e d i s t r i b u t i o n o f t h e -

show abstract

Section: Discussionsupporting

confidence: 80%

Cyclooxygenase-2 polymorphisms and the risk of esophageal adeno- or squamous cell carcinoma

Kristinsson¹,

Westerveld²,

Morsche³

et al. 2009

WJG

View full text Add to dashboard Cite

show abstract

“…Fiedler et al [41] found a similar association, most notably for the MDR1 2677GG / 3435TT haplotype with UC, but not for CD. The haplotypes investigated by Ho et al [23] showed positive (MDR1 G2677 / 3435T) and negative (MDR1 2677T / C3435) correlations with UC, and confirmed the findings of Fiedler et al [42] Haplotypes including BCRP C421A have been less frequently assessed and no associations with a combined IBD endpoint are known of to date.…”

Section: Haplotype Studiessupporting

confidence: 70%

Determination of the Single Nucleotide Polymorphisms C3435 and G2677T in MDR1 and C421A in BCRP in Blood Samples of Patients with Inflammatory Bowel Disease and Healthy Controls in the Swiss Population

2012

J Postgenom Drug Biomark Develop

View full text Add to dashboard Cite

Aims: P-glycoprotein (P-gp, ABCB1, MDR1) and breast cancer resistance protein (BCRP, ABCG2) protect the luminal cells of the gastro-intestinal tract from potentially toxic substances. Genetic polymorphisms have previously been associated with disease susceptibility, severity, and treatment prognosis of inflammatory bowel disease. We investigated the prevalence of frequent single nucleotide polymorphisms of P-gp and BCRP in the Swiss population in healthy volunteers (n = 17) and patients newly diagnosed with Crohn's Disease (CD, n = 34) or Ulcerative Colitis (UC, n = 38). Methods: DNA from peripheral blood cells was used to assess genotype and allele frequencies of MDR1 C3435T, MDR1 G2677T, and BCRP C421A. Results: Weak associations for BCRP C421A (p < 0.18) and MDR1 G2677T (p < 0.27) were seen in UC and a trend towards the wild type allele for MDR1 C3435T (p < 0.46). MDR1 3435CC / BCRP 421CC (Χ2: 1.0142, p < 0.30) in UC and MDR1 2677G / BCRP 421A (Χ2: 1.5615, p < 0.22) also weakly correlated with UC. Results for BCRP C421A in particular justify further study. Conclusions: Trends towards certain alleles and haplotypes were seen. These merit further studies in larger subgroups (e.g. by disease stage, therapy refractory patients, etc.). In the human gastrointestinal tract, P-gp is expressed predominantly apically on the epithelium of small intestine and colon, but also in the small biliary and pancreatic ductules [10]. P-gp is therefore seen as a contributor to gut mucosal defense and reduced activity is thought to be a co-factor in IBD pathogenesis [11]. P-gp is encoded by the MDR1/ABCB1 gene, located on Chromosome 7q21.1, and spans over 100 kb. However, MDR1 mRNA has a size of 4.7 kDa, implying that only a small percentage of the gene actually codes [12]. P-gp is currently the best studied ABC transporter and to date 50 single nucleotide polymorphisms (SNPs) have been identified, more than half of which reside in the coding region [13][14][15]. This interest stems from its ability to confer multidrug resistance in cancer cells by lowering the uptake of anti-cancer drugs [16]. Due to its promiscuity and localization, it also affects the bioavailability of many other drugs [17] and exposure to one of its substrates can render the cell resistant to a wide range of compounds [18]. AbstractAims: P-glycoprotein (P-gp, ABCB1, MDR1) and breast cancer resistance protein (BCRP, ABCG2) protect the luminal cells of the gastro-intestinal tract from potentially toxic substances. Genetic polymorphisms have previously been associated with disease susceptibility, severity, and treatment prognosis of inflammatory bowel disease. We investigated the prevalence of frequent single nucleotide polymorphisms of P-gp and BCRP in the Swiss population in healthy volunteers (n = 17) and patients newly diagnosed with Crohn's Disease (CD, n = 34) or Ulcerative Colitis (UC, n = 38).Methods: DNA from peripheral blood cells was used to assess genotype and allele frequencies of MDR1 C3435T, MDR1 G2677T, and BCRP C421A.Results: Weak ass...

show abstract

“…Genomic DNA was isolated from blood samples according to standard procedures with minor modifications as described previously [28]. All analyses were run blinded to the case-control status.…”

Section: Methodsmentioning

confidence: 99%

Intestinal PTGS2 mRNA Levels, PTGS2 Gene Polymorphisms, and Colorectal Carcinogenesis

et al. 2014

Self Cite

View full text Add to dashboard Cite

Background & AimsInflammation is a major risk factor for development of colorectal cancer (CRC). Prostaglandin synthase cyclooxygenase-2 (COX-2) encoded by the PTGS2 gene is the rate limiting enzyme in prostaglandin synthesis and therefore plays a distinct role as regulator of inflammation.Methods PTGS2 mRNA levels were determined in intestinal tissues from 85 intestinal adenoma cases, 115 CRC cases, and 17 healthy controls. The functional PTGS2 polymorphisms A-1195G (rs689466), G-765C (rs20417), T8473C (rs5275) were assessed in 200 CRC cases, 991 adenoma cases and 399 controls from the Norwegian KAM cohort.Results PTGS2 mRNA levels were higher in mild/moderate adenoma tissue compared to morphologically normal tissue from the same individual (P<0.0001) and (P<0.035) and compared to mucosa from healthy individuals (P<0.0039) and (P<0.0027), respectively. In CRC patients, PTGS2 mRNA levels were 8–9 times higher both in morphologically normal tissue and in cancer tissue, compared to healthy individuals (P<0.0001). PTGS2 A-1195G variant allele carriers were at reduced risk of CRC (odds ratio (OR) = 0.52, 95% confidence interval (95% CI): 0.28–0.99, P = 0.047). Homozygous carriers of the haplotype encompassing the A-1195G and G-765C wild type alleles and the T8473C variant allele (PTGS2 AGC) were at increased risk of CRC as compared to homozygous carriers of the PTGS2 AGT (A-1195G, G-765C, T8473C) haplotype (OR = 5.37, 95% CI: 1.40–20.5, P = 0.014). No association between the investigated polymorphisms and PTGS2 mRNA levels could be detected.ConclusionHigh intestinal PTGS2 mRNA level is an early event in colorectal cancer development as it occurs already in mild/moderate dysplasia. PTGS2 polymorphisms that have been associated with altered PTGS2 mRNA levels/COX-2 activity in some studies, although not the present study, were associated with colorectal cancer risk. Thus, both PTGS2 polymorphisms and PTGS2 mRNA levels may provide information regarding CRC risk.

show abstract

Cyclooxygenase-2, multidrug resistance 1, and breast cancer resistance protein gene polymorphisms and inflammatory bowel disease in the Danish population

Cited by 32 publications

References 45 publications

Cyclooxygenase-2 polymorphisms and the risk of esophageal adeno- or squamous cell carcinoma

Cyclooxygenase-2 polymorphisms and the risk of esophageal adeno- or squamous cell carcinoma

Determination of the Single Nucleotide Polymorphisms C3435 and G2677T in MDR1 and C421A in BCRP in Blood Samples of Patients with Inflammatory Bowel Disease and Healthy Controls in the Swiss Population

Intestinal PTGS2 mRNA Levels, PTGS2 Gene Polymorphisms, and Colorectal Carcinogenesis

Contact Info

Product

Resources

About