Mona Sæbø | Telemark University College (original) (raw)

Papers by Mona Sæbø

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

BMC cancer, 2006

The majority of colorectal cancer (CRC) cases develop through the adenoma-carcinoma pathway. If a... more 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. 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. 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...

Research paper thumbnail of The ratio of Matriptase/HAI-1 mRNA is higher in colorectal cancer adenomas and carcinomas than corresponding tissue from control individuals

BMC cancer, 2006

It has recently been shown that overexpression of the serine protease, matriptase, in transgenic ... more It has recently been shown that overexpression of the serine protease, matriptase, in transgenic mice causes a dramatically increased frequency of carcinoma formation. Overexpression of HAI-1 and matriptase together changed the frequency of carcinoma formation to normal. This suggests that the ratio of matriptase to HAI-1 influences the malignant progression. The aim of this study has been to determine the ratio of matriptase to HAI-1 mRNA expression in affected and normal tissue from individuals with colorectal cancer adenomas and carcinomas as well as in healthy individuals, in order to determine at which stages a dysregulated ratio of matriptase/HAI-1 mRNA is present during carcinogenesis. Using quantitative RT-PCR, we have determined the mRNA levels for matriptase and HAI-1 in colorectal cancer tissue (n = 9), severe dysplasia (n = 15), mild/moderate dysplasia (n = 21) and in normal tissue from the same individuals. In addition, corresponding tissue was examined from healthy vol...

Research paper thumbnail of Association between cigarette smoking, APC mutations and the risk of developing sporadic colorectal adenomas and carcinomas

BMC cancer, 2006

The association between colorectal cancer (CRC) and smoking has not been consistent. Incomplete s... more The association between colorectal cancer (CRC) and smoking has not been consistent. Incomplete smoking history and association to a specific subset of CRC tumors have been proposed as explanations. The adenomatous polyposis coli (APC) gene has been reported to have a "gatekeeper" function in the colonic mucosa. To evaluate the hypothesis that cigarette smoking is associated with adenoma and carcinoma development and further to investigate whether this association is due to mutations in the APC gene, we used a study population consisting of 133 cases (45 adenomas and 88 carcinomas) and 334 controls. All tumors were sequenced in the mutation cluster region (MCR) of the APC gene. Cases and controls were drawn from a homogeneous cohort of Norwegian origin. The mutational spectra of the APC gene revealed no difference in frequencies of mutations in cases based on ever and never smoking status. An overall case-control association was detected for adenomas and "ever smoking...

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

BMC cancer, 2006

Genetic polymorphisms in DNA repair genes may influence individual variation in DNA repair capaci... more 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. 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 Arg194Trp, Arg280His, Arg399Gln, XRCC3 Thr241Met and XPD Lys751Gln), 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 consumpti...

Research paper thumbnail of High ABCC2 and Low ABCG2 Gene Expression Are Early Events in the Colorectal Adenoma-Carcinoma Sequence

PLOS ONE, 2015

Development of colorectal cancer (CRC) may result from a dysfunctional interplay between diet, gu... more Development of colorectal cancer (CRC) may result from a dysfunctional interplay between diet, gut microbes and the immune system. The ABC transport proteins ABCB1 (Pglycoprotein, 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).

Research paper thumbnail of Intestinal PTGS2 mRNA Levels, PTGS2 Gene Polymorphisms, and Colorectal Carcinogenesis

PLoS ONE, 2014

Background & Aims: Inflammation is a major risk factor for development of colorectal cancer (CRC)... more Background & Aims: Inflammation 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.

Research paper thumbnail of Effects of polymorphisms in ERCC1, ASE-1 and RAI on the risk of colorectal carcinomas and adenomas: a case control study

BMC cancer, 2006

The risk of sporadic colorectal cancer is mainly associated with lifestyle factors and may be mod... more The risk of sporadic colorectal cancer is mainly associated with lifestyle factors and may be modulated by several genetic factors of low penetrance. Genetic variants represented by single nucleotide polymorphisms in genes encoding key players in the adenoma carcinoma sequence may contribute to variation in susceptibility to colorectal cancer. In this study, we aimed to evaluate whether the recently identified haplotype encompassing genes of DNA repair and apoptosis, is associated with increased risk of colorectal adenomas and carcinomas. We used a case-control study design (156 carcinomas, 981 adenomas and 399 controls) to test the association between polymorphisms in the chromosomal region 19q13.2-3, encompassing the genes ERCC1, ASE-1 and RAI, and risk of colorectal adenomas and carcinomas in a Norwegian cohort. Odds ratio (OR) and 95% confidence interval (CI) were estimated by binary logistic regression model adjusting for age and gender. The ASE-1 polymorphism was associated wi...

Research paper thumbnail of Correction: Low ABCB1 Gene Expression Is an Early Event in Colorectal Carcinogenesis

PLoS ONE, 2013

The ABCB1/MDR1 gene product ABCB1/P-glycoprotein is implicated in the development of colorectal c... more 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.

Research paper thumbnail of ID: 310 The ratio of Matriptase/HAI-1 mRNA is higher in colorectal cancer adenomas and carcinomas than corresponding tissue from control individuals

Journal of Thrombosis and Haemostasis, 2006

ABSTRACT Purpose: It has recently been shown that overexpression of the serine protease, matripta... more ABSTRACT Purpose: It has recently been shown that overexpression of the serine protease, matriptase, in transgenic mice causes a dramatic increased frequency of carcinoma formation. Overexpression of HAI-1 and matriptase together changed the frequency of carcinoma formation to normal. This suggests that the ratio of matriptase to HAI-1 influences the malignant progression rather than the expression level per set. Dysregulated matriptase/HAI-1 ratio has been shown to strongly potentiate chemical carcinogenesis. This aim of this study has been to determine the ratio of matriptase to HAI-1 mRNA expression in affected and normal tissue from individuals with colorectal cancer adenomas and carcinomas as well as in healthy individuals, in order to determine whether a dysregulated ratio of matriptase/HAI-1 mRNA is present during carcinogenesis. Experimental design: Using RT-PCR, we have determined the mRNA levels for matriptase and HAI-1 in colorectal cancer tissue (n=9), severe dysplasia (n=15), mild/moderate dysplasia (n=21) and in normal tissue from the same individuals. In addition, corresponding tissue was examined from healthy volunteers (n=10). Matriptase and HAI-1 mRNA levels were normalized to beta-actin. Results: Matriptase levels showed a modest down-regulation in carcinomas, whereas HAI-1 expression was extensively down-regulated in tissue displaying mild/moderate dysplasia and in normal and affected tissue from individuals with severe dysplasia or carcinomas. Conclusions: Both colorectal adenomas and carcinomas displayed a higher matriptase/HAI-1 mRNA ratio than corresponding normal tissue from the same individuals or healthy controls. This shows that dysregulation of the matriptase/HAI-1 mRNA occurs early during carcinogenesis and is maintained during all stages of malignant progression.

Research paper thumbnail of GPX Pro198Leu and OGG1 Ser326Cys polymorphisms and risk of development of colorectal adenomas and colorectal cancer

Cancer Letters, 2005

HANSEN, R.; SAEBØ, M.; SKJELBRED, C.F.; NEXØ, B.A.; HAGEN, P.C.; BOCK, G., LOTHE, I.M.B.; JOHNSON... more HANSEN, R.; SAEBØ, M.; SKJELBRED, C.F.; NEXØ, B.A.; HAGEN, P.C.; BOCK, G., LOTHE, I.M.B.; JOHNSON, E.; AASE, S.; HANSTEEN, I.L.; VOGEL, U.; KURE, E.H.; GPX Pro198Leu and OGG1 Ser326Cys polymorphisms and risk of development of colorectal adenomas and colorectal cancer.

Research paper thumbnail of 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

BMC Medical Genetics, 2009

Smoking, dietary factors, and alcohol consumption are known life style factors contributing to ga... more 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(MDR1/ABCB1) 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, Pglycoprotein 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 MDR1 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 MDR1 polymorphism was associated with risk of colorectal adenoma (CA) and CRC in the Norwegian population.

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

BMC Cancer, 2007

Background: It has recently been shown that NDRG2 mRNA is down-regulated or undetectable in sever... more Background: It has recently been shown that NDRG2 mRNA is down-regulated or undetectable in several human cancers and cancer cell-lines. Although the function of NDRG2 is unknown, high NDRG2 expression correlates with improved prognosis in high-grade gliomas. The aim of this study has been to examine NDRG2 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 NDRG2 down-regulation occurs during colonic carcinogenesis.

Research paper thumbnail of Molecular responses to toxicological stressors: Profiling microRNAs in wild Atlantic salmon (Salmo salar) exposed to acidic aluminum-rich water

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

BMC Cancer, 2007

The risk of sporadic colorectal cancer (CRC) is mainly associated with lifestyle factors, particu... more 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.

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

BMC cancer, 2006

The majority of colorectal cancer (CRC) cases develop through the adenoma-carcinoma pathway. If a... more 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. 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. 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...

Research paper thumbnail of The ratio of Matriptase/HAI-1 mRNA is higher in colorectal cancer adenomas and carcinomas than corresponding tissue from control individuals

BMC cancer, 2006

It has recently been shown that overexpression of the serine protease, matriptase, in transgenic ... more It has recently been shown that overexpression of the serine protease, matriptase, in transgenic mice causes a dramatically increased frequency of carcinoma formation. Overexpression of HAI-1 and matriptase together changed the frequency of carcinoma formation to normal. This suggests that the ratio of matriptase to HAI-1 influences the malignant progression. The aim of this study has been to determine the ratio of matriptase to HAI-1 mRNA expression in affected and normal tissue from individuals with colorectal cancer adenomas and carcinomas as well as in healthy individuals, in order to determine at which stages a dysregulated ratio of matriptase/HAI-1 mRNA is present during carcinogenesis. Using quantitative RT-PCR, we have determined the mRNA levels for matriptase and HAI-1 in colorectal cancer tissue (n = 9), severe dysplasia (n = 15), mild/moderate dysplasia (n = 21) and in normal tissue from the same individuals. In addition, corresponding tissue was examined from healthy vol...

Research paper thumbnail of Association between cigarette smoking, APC mutations and the risk of developing sporadic colorectal adenomas and carcinomas

BMC cancer, 2006

The association between colorectal cancer (CRC) and smoking has not been consistent. Incomplete s... more The association between colorectal cancer (CRC) and smoking has not been consistent. Incomplete smoking history and association to a specific subset of CRC tumors have been proposed as explanations. The adenomatous polyposis coli (APC) gene has been reported to have a "gatekeeper" function in the colonic mucosa. To evaluate the hypothesis that cigarette smoking is associated with adenoma and carcinoma development and further to investigate whether this association is due to mutations in the APC gene, we used a study population consisting of 133 cases (45 adenomas and 88 carcinomas) and 334 controls. All tumors were sequenced in the mutation cluster region (MCR) of the APC gene. Cases and controls were drawn from a homogeneous cohort of Norwegian origin. The mutational spectra of the APC gene revealed no difference in frequencies of mutations in cases based on ever and never smoking status. An overall case-control association was detected for adenomas and "ever smoking...

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

BMC cancer, 2006

Genetic polymorphisms in DNA repair genes may influence individual variation in DNA repair capaci... more 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. 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 Arg194Trp, Arg280His, Arg399Gln, XRCC3 Thr241Met and XPD Lys751Gln), 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 consumpti...

Research paper thumbnail of High ABCC2 and Low ABCG2 Gene Expression Are Early Events in the Colorectal Adenoma-Carcinoma Sequence

PLOS ONE, 2015

Development of colorectal cancer (CRC) may result from a dysfunctional interplay between diet, gu... more Development of colorectal cancer (CRC) may result from a dysfunctional interplay between diet, gut microbes and the immune system. The ABC transport proteins ABCB1 (Pglycoprotein, 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).

Research paper thumbnail of Intestinal PTGS2 mRNA Levels, PTGS2 Gene Polymorphisms, and Colorectal Carcinogenesis

PLoS ONE, 2014

Background & Aims: Inflammation is a major risk factor for development of colorectal cancer (CRC)... more Background & Aims: Inflammation 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.

Research paper thumbnail of Effects of polymorphisms in ERCC1, ASE-1 and RAI on the risk of colorectal carcinomas and adenomas: a case control study

BMC cancer, 2006

The risk of sporadic colorectal cancer is mainly associated with lifestyle factors and may be mod... more The risk of sporadic colorectal cancer is mainly associated with lifestyle factors and may be modulated by several genetic factors of low penetrance. Genetic variants represented by single nucleotide polymorphisms in genes encoding key players in the adenoma carcinoma sequence may contribute to variation in susceptibility to colorectal cancer. In this study, we aimed to evaluate whether the recently identified haplotype encompassing genes of DNA repair and apoptosis, is associated with increased risk of colorectal adenomas and carcinomas. We used a case-control study design (156 carcinomas, 981 adenomas and 399 controls) to test the association between polymorphisms in the chromosomal region 19q13.2-3, encompassing the genes ERCC1, ASE-1 and RAI, and risk of colorectal adenomas and carcinomas in a Norwegian cohort. Odds ratio (OR) and 95% confidence interval (CI) were estimated by binary logistic regression model adjusting for age and gender. The ASE-1 polymorphism was associated wi...

Research paper thumbnail of Correction: Low ABCB1 Gene Expression Is an Early Event in Colorectal Carcinogenesis

PLoS ONE, 2013

The ABCB1/MDR1 gene product ABCB1/P-glycoprotein is implicated in the development of colorectal c... more 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.

Research paper thumbnail of ID: 310 The ratio of Matriptase/HAI-1 mRNA is higher in colorectal cancer adenomas and carcinomas than corresponding tissue from control individuals

Journal of Thrombosis and Haemostasis, 2006

ABSTRACT Purpose: It has recently been shown that overexpression of the serine protease, matripta... more ABSTRACT Purpose: It has recently been shown that overexpression of the serine protease, matriptase, in transgenic mice causes a dramatic increased frequency of carcinoma formation. Overexpression of HAI-1 and matriptase together changed the frequency of carcinoma formation to normal. This suggests that the ratio of matriptase to HAI-1 influences the malignant progression rather than the expression level per set. Dysregulated matriptase/HAI-1 ratio has been shown to strongly potentiate chemical carcinogenesis. This aim of this study has been to determine the ratio of matriptase to HAI-1 mRNA expression in affected and normal tissue from individuals with colorectal cancer adenomas and carcinomas as well as in healthy individuals, in order to determine whether a dysregulated ratio of matriptase/HAI-1 mRNA is present during carcinogenesis. Experimental design: Using RT-PCR, we have determined the mRNA levels for matriptase and HAI-1 in colorectal cancer tissue (n=9), severe dysplasia (n=15), mild/moderate dysplasia (n=21) and in normal tissue from the same individuals. In addition, corresponding tissue was examined from healthy volunteers (n=10). Matriptase and HAI-1 mRNA levels were normalized to beta-actin. Results: Matriptase levels showed a modest down-regulation in carcinomas, whereas HAI-1 expression was extensively down-regulated in tissue displaying mild/moderate dysplasia and in normal and affected tissue from individuals with severe dysplasia or carcinomas. Conclusions: Both colorectal adenomas and carcinomas displayed a higher matriptase/HAI-1 mRNA ratio than corresponding normal tissue from the same individuals or healthy controls. This shows that dysregulation of the matriptase/HAI-1 mRNA occurs early during carcinogenesis and is maintained during all stages of malignant progression.

Research paper thumbnail of GPX Pro198Leu and OGG1 Ser326Cys polymorphisms and risk of development of colorectal adenomas and colorectal cancer

Cancer Letters, 2005

HANSEN, R.; SAEBØ, M.; SKJELBRED, C.F.; NEXØ, B.A.; HAGEN, P.C.; BOCK, G., LOTHE, I.M.B.; JOHNSON... more HANSEN, R.; SAEBØ, M.; SKJELBRED, C.F.; NEXØ, B.A.; HAGEN, P.C.; BOCK, G., LOTHE, I.M.B.; JOHNSON, E.; AASE, S.; HANSTEEN, I.L.; VOGEL, U.; KURE, E.H.; GPX Pro198Leu and OGG1 Ser326Cys polymorphisms and risk of development of colorectal adenomas and colorectal cancer.

Research paper thumbnail of 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

BMC Medical Genetics, 2009

Smoking, dietary factors, and alcohol consumption are known life style factors contributing to ga... more 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(MDR1/ABCB1) 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, Pglycoprotein 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 MDR1 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 MDR1 polymorphism was associated with risk of colorectal adenoma (CA) and CRC in the Norwegian population.

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

BMC Cancer, 2007

Background: It has recently been shown that NDRG2 mRNA is down-regulated or undetectable in sever... more Background: It has recently been shown that NDRG2 mRNA is down-regulated or undetectable in several human cancers and cancer cell-lines. Although the function of NDRG2 is unknown, high NDRG2 expression correlates with improved prognosis in high-grade gliomas. The aim of this study has been to examine NDRG2 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 NDRG2 down-regulation occurs during colonic carcinogenesis.

Research paper thumbnail of Molecular responses to toxicological stressors: Profiling microRNAs in wild Atlantic salmon (Salmo salar) exposed to acidic aluminum-rich water

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

BMC Cancer, 2007

The risk of sporadic colorectal cancer (CRC) is mainly associated with lifestyle factors, particu... more 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.