Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001430 (adenoma)
 21,222 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Except for hereditary disease, genetic factors that contribute to the development of renal epithelial tumors are unknown. There is a possibility that the MDR1 encoded plasma membrane transporter P-glycoprotein (PGP) influences the risk of development of renal neoplasms. PGP is known to be involved in uptake, binding, transport, and distribution of xenobiotics. There is evidence that the MDR1(C3435T) polymorphism drives expression and modulates disease risk. In an explorational case-control study, constitutional genotype frequencies were established at MDR1(C3435T) of 537 healthy control subjects and compared with those of 212 patients with renal epithelial tumors. There were 179 clear cell renal cell carcinoma (CCRCC) and 33 tumors collectively assigned as non-CCRCC. In a second study, genotypes of another 150 healthy control subjects and 50 patients with three non-CCRCC types (26 papillary RCC, 11 chromophobe RCC, and 13 renal oncocytic adenoma) were compared. PCR-restriction fragment length polymorphism-based analysis of constitutional DNA, and statistical analysis were applied. PGP expression was analyzed by quantitative immunohistochemistry. The explorational study showed a significant association between T allele frequency and the occurrence of tumors (P = 0.007). When tumors were histopathologically distinguished into frequent CCRCC and less frequent non-CCRCC, both patient groups contributed to this effect with a seemingly strong influence by the latter (P = 0.0419). The second study established the T allele as a risk factor especially for non-CCRCC (P = 0.0005) with the highest risk for homozygote TT allele carriers (P < 0.0001). Independently, MDR1(C3435T) genotype associated variations in PGP expression were shown in normal renal parenchyma with a 1.5-fold difference of median values (TT, 1.9; CC, 2.8; P = 0.0065). The data provide evidence for PGP to influence the susceptibility to develop renal epithelial tumors by virtue of its MDR1(C3435T) polymorphism and changes in expression. Especially T and TT carriers are at risk for developing non-CCRCC, i.e., papillary and chromophobe RCC as well as oncocytic adenomas.
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PMID:Association of the P-glycoprotein transporter MDR1(C3435T) polymorphism with the susceptibility to renal epithelial tumors. 1208 80

Hepatocellular adenoma and focal nodular hyperplasia (FNH) are benign liver tumours. The differential diagnosis of these lesions and of well- to moderately differentiated hepatocellular carcinomas is often difficult but is very important in view of their different treatment. Although neither type of lesion is connected to the biliary tree, FNHs are cholestatic, whereas this is rarely the case for hepatocellular adenomas. This suggests that hepatocellular uptake and secretion of bile constituents is different in FNHs compared to adenomas. We therefore evaluated the expression and localization of hepatic transporters in hepatocellular adenomas, different types of FNH and well- to moderately differentiated hepatocellular carcinomas in non-cirrhotic liver and compared them with normal liver, using real-time RT-PCR and (semi-)quantitative immunohistochemistry. The parenchymal expression of the uptake transporter OATP2/8 (OATP1B1/3) was minimal or absent in adenoma, while there was strong and diffuse expression in FNH. We observed diffuse parenchymal expression of the basolateral export pump MRP3 in adenomas, while only reactive bile ductules and adjacent cholestatic hepatocytes were MRP3-positive in FNH. The MRP3/OATP2/8 expression pattern of atypical FNHs resembled that of adenomas, suggesting that both types of lesion are related. Most hepatocellular carcinomas showed decreased expression of one or more of the canalicular transporters (MDR1, MDR3, BSEP). The differences in transporter expression profile between FNHs and adenomas are most likely pathogenetically important and may explain why only FNHs are cholestatic. The finding that each type of focal lesion in non-cirrhotic liver has a specific transporter expression pattern may be useful in the establishment of a correct diagnosis by imaging or on needle biopsy.
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PMID:Diagnostic and pathogenetic implications of the expression of hepatic transporters in focal lesions occurring in normal liver. 1616 Oct 6

The ABCB1/MDR1 gene product ABCB1/P-glycoprotein is implicated in the development of colorectal cancer (CRC). NFKB1 encodes transcription factors regulating expression of a number of genes including ABCB1. We have previously found association between the ABCB1 C-rs3789243-T polymorphism and CRC risk and interactions between the ABCB1 C-rs3789243-T and C3435T polymorphisms and meat intake in relation to CRC risk (Andersen, BMC Cancer, 2009, 9, 407). ABCB1 and NFKB1 mRNA levels were assessed in intestinal tissue from 122 CRC cases, 101 adenoma cases (12 with severe dysplasia, 89 with mild-moderate dysplasia) and from 18 healthy individuals, together with gene polymorphisms in ABCB1 and NFKB1. ABCB1 mRNA levels were highest in the healthy individuals and significantly lower in mild/moderate and severe dysplasia tissue (P<0.05 for both), morphologically normal tissues close to the tumour (P<0.05), morphologically normal tissue at a distance from the tumour (P<0.05) and CRC tissue (P<0.001). Furthermore, ABCB1 mRNA levels were lower in adenomas and carcinomas compared to morphologically normal tissue from the same individuals (P<0.01). The ABCB1 C-rs3789243-T and NFKB1 -94ins/del homozygous variant genotypes were associated with low ABCB1 mRNA levels in morphologically normal sigmoid tissue from adenoma cases (P<0.05 for both). NFKB1 mRNA levels were lower in both tumour and normal tissue from cancer patients (P<0.001) as compared to healthy individuals but we were unable to show association between NFKB1 -94ins/del genotype and NFKB1 mRNA levels. This study suggests that low ABCB1 mRNA levels are an early event in CRC development and that the two polymorphisms affect ABCB1 mRNA levels whereas low NFKB1 mRNA levels occur later in carcinogenesis. Low ABCB1 protein levels may promote colorectal carcinogenesis through increasing intracellular exposure to carcinogenic ABCB1 substrates.
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PMID:Low ABCB1 gene expression is an early event in colorectal carcinogenesis. 2397 25

Development of colorectal cancer (CRC) may result from a dysfunctional interplay between diet, gut microbes and the immune system. The ABC transport proteins ABCB1 (P-glycoprotein, Multidrug resistance protein 1, MDR1), ABCC2 (MRP2) and ABCG2 (BCRP) are involved in transport of various compounds across the epithelial barrier. Low mRNA level of ABCB1 has previously been identified as an early event in colorectal carcinogenesis (Andersen et al., PLoS One. 2013 Aug 19;8(8):e72119). ABCC2 and ABCG2 mRNA levels were assessed in intestinal tissue from 122 CRC cases, 106 adenoma cases (12 with severe dysplasia, 94 with mild-moderate dysplasia) and from 18 controls with normal endoscopy. We found significantly higher level of ABCC2 in adenomas with mild to moderate dysplasia and carcinoma tissue compared to the levels in unaffected tissue from the same individual (P = 0.037, P = 0.037, and P<0.0001) and in carcinoma and distant unaffected tissue from CRC cases compared to the level in the healthy individuals (P = 0.0046 and P = 0.036). Furthermore, ABCG2 mRNA levels were significantly lower in adenomas and carcinomas compared to the level in unaffected tissue from the same individuals and compared to tissue from healthy individuals (P<0.0001 for all). The level of ABCB2 in adjacent normal tissue was significantly higher than in tissue from healthy individuals (P = 0.011). In conclusion, this study found that ABCC2 and ABCG2 expression levels were altered already in mild/moderate dysplasia in carcinogenesis suggesting that these ABC transporters are involved in the early steps of carcinogenesis as previously reported for ABCB1. These results suggest that dysfunctional transport across the epithelial barrier may contribute to colorectal carcinogenesis.
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PMID:High ABCC2 and low ABCG2 gene expression are early events in the colorectal adenoma-carcinoma sequence. 2579 71

Colorectal cancer has been considered as one of the complicated multi-stage processes after adenoma-carcinoma sequence. Therefore, studies of the molecular dysregulation basis could present information on the recognition of the potent biomarkers and treatment targets for this disease. Even though outcomes of the patients with colorectal cancer have been improved largely with current annual screening plans, it is necessary to have reliable prognostic biomarkers because of the disease heterogeneity. There is a significant relationship between SNP in IL1RN* 2 (IL1ra), -509 C/T (TGFB1), rs11556218 T>G and rs4778889 T/C (IL16), miRNA-binding site polymorphisms in IL16, rs4464148 (SMAD7), rs6983267 (EGF), GSTT1, TACG haplotype (CTLA4), 1793G> A (MTHFR), Leu/Leu genotype of (EXO1), -137 G/C (IL18), C/T genotype (XRCC3), I3434T (XRCC7), MGMT, C3435T (MDR1), ff genotype of FokI, 677CT+TT (MTHFR), G2677T/A (MDR1) and CRC. Increased risk has been observed in VDR ApaI genotype "aa". Finally, the protective effect has been explored in the TACA haplotype (CTLA4). According to the findings, the genetic polymorphisms in the immunity-associated genes are related to the CRC amongst the Iranian patients. Therefore, more large-scale functional investigations are necessary for confirming the results.
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PMID:Single Nucleotide Variants Associated with Colorectal Cancer Among Iranian Patients: A Narrative Review. 3258 66