No evidence that polymorphisms in CYP2C8, CYP2C9, UGT1A6, PPARδ and PPARγ act as modifiers of the protective effect of regular NSAID use on the risk of colorectal carcinoma

McGreavey, L; Turner, Faye; Smith, Gillian; Boylan, Katherine E.; Bishop, D. Timothy; Forman, David; Wolf, C. Roland; Barrett, Jennifer H.

doi:10.1097/01.fpc.0000174786.85238.63

Cited by 49 publications

(43 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In spite of these indications, however, whether PPARd is a good target for chemoprevention and/or treatment of CRC remains controversial. It has been reported that a polymorphism in PPARd modifies the protective effects of nonsteroidal anti-inflammatory drugs on colorectal adenomas (Siezen et al, 2006), but other investigators have not reached the same conclusions in the context of CRC (McGreavey et al, 2005). As mentioned in the Introduction, PPARd was found to be unnecessary for small intestinal polyp formation (Barak et al, 2002), but PPARd attenuated polyp formation in chemical and genetic models (Harman et al, 2004;Reed et al, 2004).…”

Section: Discussionmentioning

confidence: 98%

Expression of PPARδ in multistage carcinogenesis of the colorectum: implications of malignant cancer morphology

et al. 2006

View full text Add to dashboard Cite

Whether peroxisome proliferator-activated receptor (PPAR) d is a good target for the chemoprevention and/or treatment of colorectal cancer (CRC) remains controversial. Our goal was to examine PPARd expression in multistage carcinogenesis of the colorectum and to assess the relevance of PPARd in CRC. Immunohistochemical analysis indicated that PPARd expression increased from normal mucosa to adenomatous polyps to CRC. In cancer tissues, the PPARd protein was accumulated only in those cancer cells with highly malignant morphology, as represented by a large-sized nucleus, round-shaped nucleus, and presence of clear nucleoli. Interestingly, the cancer tissue often contained both PPARd-positive and -negative areas, each retaining their respective specific morphological features. Moreover, this pattern persisted even when PPARd-positive and -negative cells were aligned next to each other within a single cancer nest or gland and was present in the majority of CRC cases. Immunohistochemistry for Ki-67 proliferation marker showed no significant correlation between Ki-67 and PPARd in CRC samples. Based on Western blot analysis and quantitative RT -PCR, high PPARd protein expression correlated with high PPARd mRNA levels. Peroxisome proliferator-activated receptor d may have a supporting role in tumorigenesis, and the close association between PPARd expression and malignant morphology of CRC cells suggests a pivotal role in cancer tissue.

show abstract

Section: Discussionmentioning

confidence: 98%

Expression of PPARδ in multistage carcinogenesis of the colorectum: implications of malignant cancer morphology

et al. 2006

View full text Add to dashboard Cite

show abstract

“…As shown in Figure 2, rs1229984 of the ADH1B gene was significantly associated with CRC in the Asian and Caucasian populations (the overall OR = 1.18, 95% CI = 1.01-1.36, p = 0.03). The meta-analysis of rs1801282/P12A/34 C > G of PPARG was involved with 14 studies (Smith et al, 2001;Jiang et al, 2005;Landi et al, 2003;McGreavey et al, 2005;Murtaugh et al, 2005;Slattery et al, 2005Slattery et al, , 2006Koh et al, 2006;Kuriki et al, 2006;Theodoropoulos et al, 2006;Vogel et al, 2007 ;Kury et al, 2008;Tsilidis et al, 2009;Crous-Bou et al, 2012) among 9132 CRC cases and 12,974 controls. Using the random-effect model, our result indicated that rs1801282-G contributed to the risk of CRC (the overall OR = 1.50, 95% CI = 1.14-1.97, p = 0.004) in the Asian and Caucasian populations.…”

Section: Quantitative Synthesismentioning

confidence: 99%

“…Associations between six single-nucleotide polymorphisms (SNPs) of the earlier-mentioned five genes and CRC have been reported in different ethnic groups (Smith et al, 2001;Landi et al, 2003Landi et al, , 2005Krzesniak et al, 2004;Jiang et al, 2005;McGreavey et al, 2005;Murtaugh et al, 2005;Slattery et al, 2005Slattery et al, , 2006Berndt et al, 2006;Huang et al, 2006;Koh et al, 2006;Kuriki et al, 2006;Matsuo et al, 2006;Moreno et al, 2006;Theodoropoulos et al, 2006;Tranah et al, 2006;Hansen et al, 2007;Kang et al, 2007;Stern et al, 2007;Vogel et al, 2007;Yin et al, 2007;Kury et al, 2008;Funke et al, 2009;Khatami et al, 2009;Tsilidis et al, 2009;Yang et al, 2009;Engin et al, 2010;Meplan et al, 2010;Loh et al, 2011;Wu et al, 2011;Crous-Bou et al, 2012;Gil et al, 2012). These six variants comprised rs12917 and rs2308321 of MGMT, rs1229984 of ADH1B, rs4880 of SOD2, rs2228001 of XPC, and rs1801282 of PPARG.…”

Section: Introductionmentioning

confidence: 99%

Association Between Six Genetic Polymorphisms and Colorectal Cancer: A Meta-Analysis

Chen

Wang

Liao

et al. 2014

Genetic Testing and Molecular Biomarkers

View full text Add to dashboard Cite

Objective: The aim of this study was to determine whether six genetic polymorphisms confer susceptibility to colorectal cancer (CRC). Methods: A systematic search for candidate genes of CRC was performed among several online databases, including PubMed, Embase, Web of Science, the Cochrane Library, CNKI, and Wanfang online libraries. After a comprehensive filtering procedure, we harvested five genes, including MGMT (rs12917 and rs2308321), ADH1B (rs1229984), SOD2 (rs4880), XPC (rs2228001), and PPARG (rs1801282). Using the REVMAN and Stata software, six meta-analyses were conducted for associations between CRC and the just-mentioned genetic variants. Results: A total of 34 comparative studies among 17,289 cases and 54,927 controls were involved in our meta-analyses. Significant association was found between ADH1B rs1229984 polymorphism and CRC ( p = 0.03, odds ratio [OR] = 1.18, 95% confidence interval [CI] = 1.01-1.36). We also found significant association between PPARG rs1801282 polymorphism and CRC ( p = 0.004, OR = 1.498, 95% CI = 1.139-1.970), and this significant association is specific in Caucasians ( p = 0.004, OR = 1.603, 95% CI = 1.165-2.205). Conclusions: The current meta-analysis has established that ADH1B (rs1229984) and PPARG (rs1801282) are two risk variants of CRC.

show abstract

“…The Colorectal Cancer Study Group tested the hypothesis that the CYP2C8 and CYP2C9 variants could change the protective effect of NSAIDs against colorectal cancer in 478 patients with colorectal cancer and 733 controls (45). While the use of NSAIDs, including ibuprofen and aspirin, was confirmed as beneficial in reducing the colorectal cancer risk, no variant modified their protective effects.…”

Section: The Relationship Between the Cyp2c8 Genotype And The Pharmacmentioning

confidence: 99%

How polymorphisms of the cytochrome P450 genes affect ibuprofen and diclofenac metabolism and toxicity / Kako polimorfizmi gena citokroma P450 utječu na metabolizam i toksičnost ibuprofena i diklofenaka

Krasniqi

Dimovski

Domjanović

et al. 2016

Archives of Industrial Hygiene and Toxicology

View full text Add to dashboard Cite

Interindividual variability in drug metabolism is an important cause of adverse drug reactions and variability in drug efficiency. Polymorphisms of cytochrome P450 (CYPs) genes have a significant effect on drug metabolism and toxicity. This review brings an update about how genetic polymorphisms of CYP2C8 and CYP2C9 enzymes affect the disposition and clinical outcomes of ibuprofen and diclofenac, two of the most common pain relievers. The most common side effects associated with the influence of CYP2C8*3 and CYP2C9*2*3 variants on ibuprofen and diclofenac pharmacokinetics are hepatotoxicity and gastrointestinal bleeding. CYP genotyping may therefore identify patients at increased risk of these adverse reactions, and these patients could have their doses adjusted or start receiving another NSAID that does not share the same metabolic pathways with ibuprofen or diclofenac. However, before genotyping is introduced into regular clinical practice, more research is needed to evaluate the effectiveness of this strategy in improving treatment with ibuprofen and diclofenac.

show abstract

No evidence that polymorphisms in CYP2C8, CYP2C9, UGT1A6, PPARδ and PPARγ act as modifiers of the protective effect of regular NSAID use on the risk of colorectal carcinoma

Abstract: Our study confirmed the reduction in risk of colorectal cancer with regular NSAID use (odds ratio (OR) = 0.73, 95% confidence interval (CI) (0.56, 0.95)) but showed that none of the polymorphic genes studied appeared to modify the protective effect of regular NSAID use.

Cited by 49 publications

References 46 publications

Expression of PPARδ in multistage carcinogenesis of the colorectum: implications of malignant cancer morphology

Expression of PPARδ in multistage carcinogenesis of the colorectum: implications of malignant cancer morphology

Association Between Six Genetic Polymorphisms and Colorectal Cancer: A Meta-Analysis

How polymorphisms of the cytochrome P450 genes affect ibuprofen and diclofenac metabolism and toxicity / Kako polimorfizmi gena citokroma P450 utječu na metabolizam i toksičnost ibuprofena i diklofenaka

Contact Info

Product

Resources

About