http://hdl.handle.net/2282/339 Search the Channel search http://teora.hit.no/dspace/simple-search http://hdl.handle.net/2282/672 Title: Meat, vegetables and genetic polymorphisms and the risk of colorectal carcinomas and adenomas <br/> <br/>Authors: Skjelbred, Camilla Furu; Sæbø, Mona; Hjartåker, Anette; Grotmol, Tom; Hansteen, Inger-Lise; Tveit, Kjell M.; Hoff, Geir; Kure, Elin H. <br/> <br/>Abstract: BACKGROUND: 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. METHODS: 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 (GSTM1, GSTT1, GSTP1 Ile105Val, EPHX1 Tyr113His and EPHX1 His139Arg), and risk of colorectal carcinomas and adenomas. Odds ratio (OR) and 95% confidence interval (95% CI) were estimated by binary logistic regression. RESULTS: 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 2nd quartile compared to the lowest quartile. For the high-risk adenomas this positive association was more obvious for the common allele (Tyr allele) of the EPHX1 codon 113 polymorphism. An association was also observed for the EPHX1 codon 113 polymorphism in the low-risk adenomas, although not as obvious. CONCLUSION: 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. Tue, 18 Dec 2007 22:58:59 GMT http://hdl.handle.net/2282/671 Title: Expression of NDRG2 is down-regulated in high-risk adenomas and colorectal carcinoma <br/> <br/>Authors: Lorentzen, Anders; Vogel, Lotte K.; Lewinsky, Rikke H.; Sæbø, Mona; Skjelbred, Camilla Furu; Godiksen, Sine; Hoff, Geir; Lothe, Inger Marie Bowitz; Ikdahl, Tone; Kure, Elin H.; Mitchelmore, Cathy <br/> <br/>Abstract: 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. METHODS: Using quantitative RT-PCR, we have determined the mRNA levels for NDRG2 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). NDRG2 levels were normalised to β-actin. RESULTS: NDRG2 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, NDRG2 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 NDRG2 levels to decrease with increasing Dukes' stage (p < 0.05). CONCLUSION: Our results demonstrate that expression of NDRG2 is down-regulated at a late stage during colorectal carcinogensis. Future studies are needed to address whether NDRG2 down-regulation is a cause or consequence of the progression of colorectal adenomas to carcinoma. Thu, 11 Oct 2007 22:58:59 GMT http://hdl.handle.net/2282/434 Title: Association between cigarette smoking, APC mutations and the risk of developing sporadic colorectal adenomas and carcinomas <br/> <br/>Authors: Sæbø, Mona; Skjelbred, Camilla Furu; Breistein, Rebecca; Lothe, Inger Marie Bowitz; Hagen, Per Chr.; Bock, Günther; Hansteen, Inger-Lise; Kure, Elin H. <br/> <br/>Abstract: BACKGROUND: 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. METHODS: 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. RESULTS: 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" OR = 1.73 (95% CI 0.83-3.58). For CRC cases several smoking parameters for dose and duration were used. We detected an association for all smoking parameters and "duration of smoking > 30 years", yielded a statistically significant OR = 2.86 (1.06-7.7). When cases were divided based on APC truncation mutation status, an association was detected in adenomas without APC mutation in relation to "ever smoking", with an OR = 3.97 (1.26-12.51). For CRC cases without APC mutation "duration of smoking > 30 years", yielded a statistically significant OR = 4.06 (1.20-13.7). The smoking parameter "starting smoking > or = 40 years ago" was only associated with CRC cases with APC mutations, OR = 2.0 (0.34-11.95). A case-case comparison revealed similar findings for this parameter, OR = 2.24 (0.73-6.86). CONCLUSION: Our data suggest an association between smoking and adenoma and CRC development. This association was strongest for cases without APC truncation mutation. This may implicate other factors in development of these tumors. The association detected between smoking and CRC cases with APC mutation was in relationship to the smoking parameter "starting smoking > or = 40 years ago", a time period long enough to proceed CRC initiation. Thu, 16 Mar 2006 22:58:59 GMT http://hdl.handle.net/2282/433 Title: GPX Pro198Leu and OGG1 Ser326Cys polymorphisms and risk of development of colorectal adenomas and colorectal cancer <br/> <br/>Authors: Hansen, Rikke; Sæbø, Mona; Skjelbred, Camilla Furu; Nexø, Bjørn Andersen; Hagen, Per Chr.; Bock, Günther; Lothe, Inger Marie Bowitz; Johnson, Egil; Aase, Steinar; Hansteen, Inger-Lise; Vogel, Ulla; Kure, Elin H. <br/> <br/>Abstract: Little is known about genetic risk factors for colorectal cancer. We assessed the association between polymorphisms in two genes involved in DNA repair of oxidative stress, GPX and OGG1, and risk of colorectal carcinoma or adenomas. We studied 166 cases with adenocarcinoma, 974 with adenomas and 397 controls recruited from the Norwegian cohort NORCCAP. No associations were found between the polymorphism GPX Pro198Leu and risk of colorectal adenomas or carcinomas. Carriers of the variant allele OGG1 Ser326Cys polymorphism had a lowered risk of colorectal cancer, OR=0.56 (95% confidence interval 0.33-0.95), while no association were found with risk of adenomas. This indicates that a low repair capacity of oxidative DNA damage may not be a risk factor for development of colorectal adenomas or carcinoma. Fri, 29 Oct 2004 22:58:59 GMT