Expression of NDRG2 is down-regulated in high-risk adenomas and colorectal carcinoma

<p>Abstract</p> <p>Background</p> <p>It has recently been shown that <it>NDRG2 </it>mRNA is down-regulated or undetectable in several human cancers and cancer cell-lines. Although the function of NDRG2 is unknown, high <it>NDRG2 </it>expression correlates with improved prognosis in high-grade gliomas. The aim of this study has been to examine <it>NDRG2 </it>mRNA expression in colon cancer. By examining affected and normal tissue from individuals with colorectal adenomas and carcinomas, as well as in healthy individuals, we aim to determine whether and at which stages <it>NDRG2 </it>down-regulation occurs during colonic carcinogenesis.</p> <p>Methods</p> <p>Using quantitative RT-PCR, we have determined the mRNA levels for <it>NDRG2 </it>in low-risk (n = 15) and high-risk adenomas (n = 57), colorectal carcinomas (n = 50) and corresponding normal tissue, as well as control tissue from healthy individuals (n = 15). <it>NDRG2 </it>levels were normalised to <it>β-actin</it>.</p> <p>Results</p> <p><it>NDRG2 </it>mRNA levels were lower in colorectal carcinomas compared to normal tissue from the control group (p < 0.001). When comparing adenomas/carcinomas with adjacent normal tissue from the same individual, <it>NDRG2 </it>expression levels were significantly reduced in both high-risk adenoma (p < 0.001) and in colorectal carcinoma (p < 0.001). There was a trend for <it>NDRG2 </it>levels to decrease with increasing Dukes' stage (p < 0.05).</p> <p>Conclusion</p> <p>Our results demonstrate that expression of <it>NDRG2 </it>is down-regulated at a late stage during colorectal carcinogensis. Future studies are needed to address whether <it>NDRG2 </it>down-regulation is a cause or consequence of the progression of colorectal adenomas to carcinoma.</p

Increased mRNA expression levels of ERCC1, OGG1 and RAI in colorectal adenomas and carcinomas

BACKGROUND: The majority of colorectal cancer (CRC) cases develop through the adenoma-carcinoma pathway. If an increase in DNA repair expression is detected in both early adenomas and carcinomas it may indicate that low repair capacity in the normal mucosa is a risk factor for adenoma formation. METHODS: We have examined mRNA expression of two DNA repair genes, ERCC1 and OGG1 as well as the putative apoptosis controlling gene RAI, in normal tissues and lesions from 36 cases with adenomas (mild/moderat n = 21 and severe n = 15, dysplasia) and 9 with carcinomas. RESULTS: Comparing expression levels of ERCC1, OGG1 and RAI between normal tissue and all lesions combined yielded higher expression levels in lesions, 3.3-fold higher (P = 0.005), 5.6-fold higher(P < 3·10(-5)) and 7.7-fold higher (P = 0.0005), respectively. The levels of ERCC1, OGG1 and RAI expressions when comparing lesions, did not differ between adenomas and CRC cases, P = 0.836, P = 0.341 and P = 0.909, respectively. When comparing expression levels in normal tissue, the levels for OGG1 and RAI from CRC cases were significantly lower compared to the cases with adenomas, P = 0.012 and P = 0.011, respectively. CONCLUSION: Our results suggest that increased expression of defense genes is an early event in the progression of colorectal adenomas to carcinomas

The multidrug resistance 1 (MDR1) gene polymorphism G-rs3789243-A is not associated with disease susceptibility in Norwegian patients with colorectal adenoma and colorectal cancer; a case control study

<p>Abstract</p> <p>Background</p> <p>Smoking, dietary factors, and alcohol consumption are known life style factors contributing to gastrointestinal carcinogenesis. Genetic variations in carcinogen handling may affect cancer risk. The multidrug resistance 1(<it>MDR1/ABCB1</it>) gene encodes the transport protein P-glycoprotein (a phase III xenobiotic transporter). P-glycoprotein is present in the intestinal mucosal lining and restricts absorption of certain carcinogens, among these polycyclic aromatic hydrocarbons. Moreover, P-glycoprotein transports various endogenous substrates such as cytokines and chemokines involved in inflammation, and may thereby affect the risk of malignity. Hence, genetic variations that modify the function of P-glycoprotein may be associated with the risk of colorectal cancer (CRC). We have previously found an association between the <it>MDR1 </it>intron 3 G-rs3789243-A polymorphism and the risk of CRC in a Danish study population. The aim of this study was to investigate if this <it>MDR1 </it>polymorphism was associated with risk of colorectal adenoma (CA) and CRC in the Norwegian population.</p> <p>Methods</p> <p>Using a case-control design, the association between the <it>MDR1 </it>intron 3 G-rs3789243-A polymorphism and the risk of colorectal carcinomas and adenomas in the Norwegian population was assessed in 167 carcinomas, 990 adenomas, and 400 controls. Genotypes were determined by allelic discrimination. Odds ratio (OR) and 95 confidence interval (95% CI) were estimated by binary logistic regression.</p> <p>Results</p> <p>No association was found between the <it>MDR1 </it>polymorphism (G-rs3789243-A) and colorectal adenomas or cancer. Carriers of the variant allele of MDR1 intron 3 had odds ratios (95% CI) of 0.97 (0.72–1.29) for developing adenomas, and 0.70 (0.41–1.21) for colorectal cancer, respectively, compared to homozygous wild type carriers.</p> <p>Conclusion</p> <p>The <it>MDR1 </it>intron 3 (G-rs3789243-A) polymorphism was not associated with a risk of colorectal adenomas or carcinomas in the present Norwegian study group. Thus, this <it>MDR1 </it>polymorphism does not seem to play an important role in colorectal carcinogenesis in this population.</p

Polymorphisms of the XRCC1, XRCC3 and XPD genes and risk of colorectal adenoma and carcinoma, in a Norwegian cohort: a case control study

BACKGROUND: Genetic polymorphisms in DNA repair genes may influence individual variation in DNA repair capacity, which may be associated with risk of developing cancer. For colorectal cancer the importance of mutations in mismatch repair genes has been extensively documented. Less is known about other DNA repair pathways in colorectal carcinogenesis. In this study we have focused on the XRCC1, XRCC3 and XPD genes, involved in base excision repair, homologous recombinational repair and nucleotide excision repair, respectively. METHODS: We used a case-control study design (157 carcinomas, 983 adenomas and 399 controls) to test the association between five polymorphisms in these DNA repair genes (XRCC1 Arg(194)Trp, Arg(280)His, Arg(399)Gln, XRCC3 Thr(241)Met and XPD Lys(751)Gln), and risk of colorectal adenomas and carcinomas in a Norwegian cohort. Odds ratio (OR) and 95% confidence interval (95% CI) were estimated by binary logistic regression model adjusting for age, gender, cigarette smoking and alcohol consumption. RESULTS: The XRCC1 280His allele was associated with an increased risk of adenomas (OR 2.30, 95% CI 1.19–4.46). The XRCC1 399Gln allele was associated with a reduction of risk of high-risk adenomas (OR 0.62, 95% CI 0.41–0.96). Carriers of the variant XPD 751Gln allele had an increased risk of low-risk adenomas (OR 1.40, 95% CI 1.03–1.89), while no association was found with risk of carcinomas. CONCLUSION: Our results suggest an increased risk for advanced colorectal neoplasia in individuals with the XRCC1 Arg(280)His polymorphism and a reduced risk associated with the XRCC1 Arg(399)Gln polymorphism. Interestingly, individuals with the XPD Lys(751)Gln polymorphism had an increased risk of low-risk adenomas. This may suggest a role in regression of adenomas

Meat, vegetables and genetic polymorphisms and the risk of colorectal carcinomas and adenomas

<p>Abstract</p> <p>Background</p> <p>The risk of sporadic colorectal cancer (CRC) is mainly associated with lifestyle factors, particularly dietary factors. Diets high in red meat and fat and low in fruit and vegetables are associated with an increased risk of CRC. The dietary effects may be modulated by genetic polymorphisms in biotransformation genes. In this study we aimed to evaluate the role of dietary factors in combination with genetic factors in the different stages of colorectal carcinogenesis in a Norwegian population.</p> <p>Methods</p> <p>We used a case-control study design (234 carcinomas, 229 high-risk adenomas, 762 low-risk adenomas and 400 controls) to test the association between dietary factors (meat versus fruit, berries and vegetables) genetic polymorphisms in biotransformation genes (<it>GSTM1</it>, <it>GSTT1</it>, <it>GSTP1 </it>Ile¹⁰⁵Val, <it>EPHX1 </it>Tyr¹¹³His and <it>EPHX1 </it>His¹³⁹Arg), and risk of colorectal carcinomas and adenomas. Odds ratio (OR) and 95% confidence interval (95% CI) were estimated by binary logistic regression.</p> <p>Results</p> <p>A higher ratio of total meat to total fruit, berry and vegetable intake was positively associated with both high and low-risk adenomas, with approximately twice the higher risk in the 2^ndquartile compared to the lowest quartile. For the high-risk adenomas this positive association was more obvious for the common allele (Tyr allele) of the <it>EPHX1 </it>codon 113 polymorphism. An association was also observed for the <it>EPHX1 </it>codon 113 polymorphism in the low-risk adenomas, although not as obvious.</p> <p>Conclusion</p> <p>Although, the majority of the comparison groups are not significant, our results suggest an increased risk of colorectal adenomas in individuals for some of the higher ratios of total meat to total fruit, berry and vegetable intake. In addition the study supports the notion that the biotransformation enzymes GSTM1, GSTP1 and EPHX1 may modify the effect of dietary factors on the risk of developing colorectal carcinoma and adenoma.</p

Patterns of Tetracapsuloides bryosalmonae infection of three salmonid species in large, deep Norwegian lakes

Proliferative kidney disease (PKD), caused by the myxozoan endoparasite Tetracapsuloides bryosalmonae, is of serious ecological and economical concern to wild and farmed salmonids. Wild salmonid populations have declined due to PKD, primarily in rivers, in Europe and North America. Deep lakes are also important habitats for salmonids, and this work aimed to investigate parasite presence in five deep Norwegian lakes. Kidney samples from three salmonid species from deep lakes were collected and tested using real-time PCR to detect PKD parasite presence. We present the first detection of T. bryosalmonae in European whitefish in Norway for the first time, as well as the first published documentation of the parasite in kidneys of Arctic charr, brown trout and whitefish in four lakes. The observed prevalence of the parasite was higher in populations of brown trout than of Arctic charr and whitefish. The parasite was detected in farmed, but not in wild, charr in one lake. This suggests a possible link with a depth of fish habitat and fewer T. bryosalmonae-infected and PKD-affected fish. Towards a warmer climate, cold hypolimnion in deep lakes may act as a refuge for wild salmonids, while cold deep water may be used to control PKD in farmed salmonids

Development and evaluation of 16 new microsatellite loci for the rock ptarmigan (Lagopus muta) and cross-species amplification for the willow grouse (L. lagopus)

Abstract The genetic markers designed for this study can facilitate future genetic studies on the rock ptarmigan (Lagopus muta). To our knowledge no microsatellite markers have ever been developed specifically for this species before. These new microsatellite markers will be useful for population genetics studies and for future conservation projects. Results Using Next Generation Sequencing 6252 potential microsatellite sequences were found. Sixteen nonpalindromic tetranucleotide microsatellites and their respective primers were selected. The markers were tested on both the rock ptarmigan and the willow grouse (L. lagopus). The number of alleles varied between 2 and 18 for the rock ptarmigan, and between 3 and 13 for the willow grouse. Expected heterozygosity was in the range 0.1244–0.8692 and 0.1358–0.8722 for the rock ptarmigan and the willow grouse, respectively

Development and evaluation of 16 new microsatellite loci for the rock ptarmigan (Lagopus muta) and cross-species amplification for the willow grouse (L. lagopus)

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver applies to the data made available in this article, unless otherwise stated.Abstract The genetic markers designed for this study can facilitate future genetic studies on the rock ptarmigan (Lagopus muta). To our knowledge no microsatellite markers have ever been developed specifically for this species before. These new microsatellite markers will be useful for population genetics studies and for future conservation projects. Results Using Next Generation Sequencing 6252 potential microsatellite sequences were found. Sixteen nonpalindromic tetranucleotide microsatellites and their respective primers were selected. The markers were tested on both the rock ptarmigan and the willow grouse (L. lagopus). The number of alleles varied between 2 and 18 for the rock ptarmigan, and between 3 and 13 for the willow grouse. Expected heterozygosity was in the range 0.1244–0.8692 and 0.1358–0.8722 for the rock ptarmigan and the willow grouse, respectively.publishedVersio

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