| 1. |
- Duell, Eric J, et al.
(författare)
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Vitamin C transporter gene (SLC23A1 and SLC23A2) polymorphisms, plasma vitamin C levels, and gastric cancer risk in the EPIC cohort
- 2013
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Ingår i: Genes & Nutrition. - : Springer Berlin/Heidelberg. - 1555-8932 .- 1865-3499. ; 8:6, s. 549-560
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Tidskriftsartikel (refereegranskat)abstract
- Vitamin C is known to protect mucosal tissues from oxidative stress and inhibit nitrosamine formation in the stomach. High consumption of fruits, particularly citrus, and higher circulating vitamin C concentrations may be inversely associated with gastric cancer (GC) risk. We investigated 20 polymorphisms in vitamin C transporter genes SCL23A1 and SCL23A2 and GC risk in 365 cases and 1,284 controls nested within the European Prospective Investigation into Cancer and Nutrition cohort. We also evaluated the association between these polymorphisms and baseline plasma vitamin C levels in a subset of participants. Four SNPs were predictors of plasma vitamin C levels (SLC23A1 rs11950646 and rs33972313; SLC23A2 rs6053005 and rs6133175) in multivariable linear regression models. One SNP (SLC23A2 rs6116569) was associated with GC risk, in particular non-cardia GC (OR = 1.63, 95 % CI = 1.11-2.39, based on 178 non-cardia cases), but this association was attenuated when plasma vitamin C was included in the logistic regression model. Haplotype analysis of SLC23A1 yielded no associations with GC. In SLC23A2, one haplotype was associated with both overall and non-cardia GC, another haplotype was associated with GC overall, and a third was associated with intestinal-type GC. Common variants in SLC23A1 and SLC23A2 may influence plasma vitamin C concentration independent of dietary intake, and variation in SLC23A2 may influence GC risk. Additional prospective studies in large populations and consortia are recommended. Investigation of variation in vitamin C transporter genes may shed light on the preventative properties of vitamin C in gastric carcinogenesis.
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| 2. |
- Glimelius, Bengt, et al.
(författare)
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U-CAN : a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden.
- 2018
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Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 57:2, s. 187-194
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Tidskriftsartikel (refereegranskat)abstract
- Background: Progress in cancer biomarker discovery is dependent on access to high-quality biological materials and high-resolution clinical data from the same cases. To overcome current limitations, a systematic prospective longitudinal sampling of multidisciplinary clinical data, blood and tissue from cancer patients was therefore initiated in 2010 by Uppsala and Umeå Universities and involving their corresponding University Hospitals, which are referral centers for one third of the Swedish population.Material and Methods: Patients with cancer of selected types who are treated at one of the participating hospitals are eligible for inclusion. The healthcare-integrated sampling scheme encompasses clinical data, questionnaires, blood, fresh frozen and formalin-fixed paraffin-embedded tissue specimens, diagnostic slides and radiology bioimaging data.Results: In this ongoing effort, 12,265 patients with brain tumors, breast cancers, colorectal cancers, gynecological cancers, hematological malignancies, lung cancers, neuroendocrine tumors or prostate cancers have been included until the end of 2016. From the 6914 patients included during the first five years, 98% were sampled for blood at diagnosis, 83% had paraffin-embedded and 58% had fresh frozen tissues collected. For Uppsala County, 55% of all cancer patients were included in the cohort.Conclusions: Close collaboration between participating hospitals and universities enabled prospective, longitudinal biobanking of blood and tissues and collection of multidisciplinary clinical data from cancer patients in the U-CAN cohort. Here, we summarize the first five years of operations, present U-CAN as a highly valuable cohort that will contribute to enhanced cancer research and describe the procedures to access samples and data.
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| 3. |
- Van Guelpen, Bethany, et al.
(författare)
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Low folate levels may protect against colorectal cancer.
- 2006
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 55:10, s. 1461-6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Dietary folate is believed to protect against colorectal cancer (CRC). However, few studies have addressed the role of circulating levels of folate. The aim of this study was to relate prediagnostic plasma folate and homocysteine concentrations and the methylenetetrahydrofolate reductase (MTHFR) 677C>T and 1298A>C polymorphisms to the risk of developing CRC. SUBJECTS: Subjects were 226 cases and 437 matched referents from the population based Northern Sweden Health and Disease Cohort. RESULTS: We observed a bell-shaped association between plasma folate concentrations and CRC risk; multivariate odds ratio for middle versus lowest quintile 2.00 (95% confidence interval (CI) 1.13-3.56). In subjects with follow up times greater than the median of 4.2 years however, plasma folate concentrations were strongly positively related to CRC risk; multivariate odds ratio for highest versus lowest quintile 3.87 (95% CI 1.52-9.87; p trend = 0.007). Homocysteine was not associated with CRC risk. Multivariate odds ratios for the MTHFR polymorphisms were, for 677 TT versus CC, 0.41 (95% CI 0.19-0.85; p trend = 0.062), and for 1298 CC versus AA, 1.62 (95% CI 0.94-2.81; p trend = 0.028). Interaction analysis suggested that the result for 1298A>C may have been largely due to linkage disequilibrium with 677C>T. The reduced CRC risk in 677 TT homozygotes was independent of plasma folate status. CONCLUSIONS: Our findings suggest a decreased CRC risk in subjects with low folate status. This possibility of a detrimental component to the role of folate in carcinogenesis could have implications in the ongoing debate in Europe concerning mandatory folate fortification of foods.
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| 4. |
- Wikberg, Maria L., et al.
(författare)
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High intratumoral expression of fibroblast activation protein (FAP) in colon cancer is associated with poorer patient prognosis.
- 2013
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Ingår i: Tumor Biology. - : Springer Netherlands. - 1010-4283 .- 1423-0380. ; 34:2, s. 1013-1020
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Tidskriftsartikel (refereegranskat)abstract
- -An active stroma is important for cancer cell invasion and metastasis. We investigated the expression of fibroblast activation protein (FAP) in relation to patient prognosis in colorectal cancer. Colorectal cancer specimens from 449 patients were immunohistochemically stained with a FAP antibody and evaluated in the tumor center and tumor front using a semiquantitative four-level scale. FAP was expressed by fibroblasts in 85-90 % of the tumors examined. High versus no/low expression in the tumor center was associated with poor prognosis (multivariate hazard ratio, HR = 1.72; 95 % CI 1.07-2.77, p = 0.025). FAP expression in the tumor front, though more frequent than in the tumor center, was not associated with prognosis. FAP expression in the tumor center was more common in specimens with positive microsatellite instability (MSI) screening status and in patients with high CpG island methylator phenotype (CIMP) status. However, inclusion of MSI screening status and CIMP status in the multivariate analysis strengthened the risk estimates for high FAP expression in the tumor center (HR = 1.89; 95 % CI 1.13-3.14; p = 0.014), emphasizing the role of FAP as an independent prognostic factor. Stromal FAP expression is common in colorectal cancer, and we conclude that high FAP expression in the tumor center, but not the tumor front, is an independent negative prognostic factor.
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| 5. |
- Öberg, Åke, 1954-, et al.
(författare)
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Are lymph node micrometastases of any clinical significance in Dukes' stages A and B colorectal cancer?
- 1998
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Ingår i: Diseases of the Colon & Rectum. - : Wolters Kluwer. - 0012-3706 .- 1530-0358. ; 41:10, s. 1244-1249
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The aim was to investigate the significance of lymph node micrometastases in Dukes Stages A and B colorectal cancer.METHODS: Archival specimens were examined from 147 patients (96 colon, 51 rectum; 44 Stage A, 103 Stage B) who had surgery between 1987 and 1994. One lymph node section from each node (colon, 1-11; median, 4; rectum, 1-15; median, 3) was examined with use of an anticytokeratin antibody.RESULTS: Forty-seven (32 percent) patients had micrometastases. At follow-up in June 1996, 23 patients had died of cancer or with known tumor relapse, after a median time of 28 (range, 5-67) months; 8 of 47 (17 percent) patients had micrometastases, 15 of 100 (15 percent) did not. No statistically significant differences were observed according to micrometastases when the results were analyzed with respect to Dukes stage or survival time. The median survival time of living patients with micrometastases was 48 (range, 18-97) months, and for patients without micrometastases, 48 (range, 19-111) months. Six of 96 living patients had a tumor relapse; three of these displayed micrometastases.CONCLUSION: Lymph node micrometastases are not a useful prognostic marker in Dukes Stages A and B and do not imply different strategies for additional therapy or follow-up.
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| 6. |
- Öberg, Åke, 1954-, et al.
(författare)
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Different occurrence of CD8+, CD45R0+, and CD68+ immune cells in regional lymph node metastases from colorectal cancer as potential prognostic predictors
- 2002
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Ingår i: International Journal of Colorectal Disease. - : Springer. - 0179-1958 .- 1432-1262. ; 17:1, s. 25-29
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: To study whether there are differences in the immunohistochemical staining of CD8, CD45R0, and CD68 of immune cells in regional lymph node metastases from colorectal cancer that are of potential interest in prognostic prediction.MATERIALS AND METHODS: Analysis of archival specimens from 93 patients operated on for colorectal cancer (based on monoclonal antibodies, the ABC technique, and semiquantitative classification).RESULTS: There was a significant difference in survival time between patients with respect to the number of positive immune cells. The cancer-specific 5-year survival rate was 77% for patients with high numbers of CD8+ cells, compared to 33% for those with lower numbers. The corresponding figures for patients with CD45R0+ cells were 66% vs. 33%, and for patients with CD68+ cells 60% vs. 38%. Significant differences remained among the 74 patients without adjuvant radio/chemotherapy regarding CD8 and CD45R0 but not CD68.CONCLUSION: The presence of CD8+, CD45R0+, and CD68+ immune cells in regional lymph node metastases may serve as predictors of patients survival in colorectal cancer Dukes' stage C.
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| 7. |
- Öberg, Åke, 1954-, et al.
(författare)
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Limited value of preoperative serum analyses of matrix metalloproteinases (MMP-2, MMP-9) and tissue inhibitors of matrix metalloproteinases (TIMP-1, TIMP-2) in colorectal cancer
- 2000
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 20:2B, s. 1085-1091
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: We studied whether preoperative serum levels of free MMP-2, the MMP-2/TIMP-2 complex, and total amounts of MMP-9, TIMP-1 and TIMP-2 correlated to the tumor stage and prognosis in colorectal cancer.METHODS: Samples from 158 patients operated on for colorectal cancer (100 colon, 58 rectum) and samples from 80 healthy blood donors were analyzed using an ELISA technique. One hundred and thirty-three patients were resected for cure, (31, 61, and 41 in Dukes' stages A, B, and C, respectively). At follow-up in January 1998, 44 patients had died from their cancer after a median time 14 months (range 2-55). Fifteen patients died without tumor relapse. Ninety-nine patients were alive after, a median time of 46 months (range 17-68).RESULTS: Wide, overlapping ranges were observed for all factors both in the patients and in the control group. The patients as compared to the control group had significantly higher levels of free MMP-2 and total amounts of MMP-9, TIMP-1 and TIMP-2, whereas the level of the MMP-2/TIMP-2 complex was significantly lower. TIMP-1 was significantly higher in Dukes' D compared to Dukes' A-C cases; the other factors did not correlate to tumor stage. Elevated TIMP-2 levels (median cut-off limit), only, correlated to worse prognosis when analysed in all patients (p < 0.05). None of the factors (median cut-off limit) correlated to survival in Dukes' A-C patients; analyses based on the upper quartile cut-off limit demonstrated that elevated MMP-2 levels correlated to shorter survival time (p < 0.05).CONCLUSION: Serum analyses of free MMP-2 the MMP-2/TIMP-2 complex and total amounts of MMP-9, TIMP-1 and TIMP-2 are of limited value for tumor staging and prognosis in colorectal cancer.
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| 8. |
- Stenling, Roger
(författare)
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The enterocyte in small intestinal adaption : an experimental and clinicopathological study with special reference to the ultrastructure of the brush border
- 1984
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The small intestine mucosa is known to be able to adapt itself to several kinds of both physiological and pathological conditions. The adaptive patterns of the structure of the enterocytes, particularly their apical surface (brush border), were studied in three models: (1) in rats, subjected to antrectomy or antral exclusion, combined with gastroduodenostomy and gastrojejunostomy; (2) in rats with alloxan diabetes; (3) in children with coeliac disease; a) in its active phase; b) after long-term treatment with gluten-free diets; c) after long-term challenge with dietary gluten following treatment; d) after short-term elimination of dietary gluten. Gut mucosa from fasting or fed, normal or sham-operated rats, fasting cats, and short-statured children with no signs of gastrointestinal disease served as controls. - The specimens were prepared for light microscopy (LM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Quantitation of structural variables was achieved by means of LM and TEM morphometrical procedures.Differentiation of the rat enterocytes from the base to the crest of the villi was structurally reflected by doubling of their apical cell area, an increase in cell height, and a decrease of both nuclear and mitochondrial volume densities. In mature normal rat enterocytes, high-power SEM showed regularly arranged, nude microvilli in thir apical surfaces, whereas in cat and man the apical surfaces were covered by a thick glycocalyx. - Fasting for 24 hours decreased the total length of the rat small intestine and the height of the enterocytes. Antrectomy and antral exclusion with gastrojejunostomy produced an increase of the apical surfaces of the enterocytes of the seif-emptying duodenal blind loop, whereas no changes occurred after antrectomy with gastroduodenostomy. In the jejunum, the apical surface area was reduced both after antrectomy and antral exclusion. In the diabetic rats a slight decrease of the apical surface area, together with an elongation of both the villi and the crypts, was observed in the jejunum, whereas no structural changes occurred in the duodenal mucosa.Both in active coeliac disease and after long-term challenge with dietary gluten, SEM analyses showed uniformly destructed villi. The apical surfaces of the enterocytes were frequently convex and irregular in size and delineation (the surface of the normal enterocytes was polygonal and flat). Ultrastructurally, the apical surfaces were severely damaged with a distortion of the glycocalyx and with marked irregularity of the microvilli. - After gluten elimination, the surface ultrastructure of the enterocytes in the coeliac gut mucosa generally showed a rapid, clear-cut restoration despite a remaining severe atrophy of the villi. Successful dietary treatment (after about one year of gluten-free diet) restored the small intestine mucosa to normal as assessed both by LM and low-power SEM. In contrast, high-power SEM often disclosed persisting lesions of the enterocytes. Another provocation with gluten for up to 9 days in clinically healed coeliac mucosa did not significantly alter the surface ultrastructure of the enterocytes.
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| 9. |
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| 10. |
- Agudo, Antonio, et al.
(författare)
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Polymorphisms in metabolic genes related to tobacco smoke and the risk of gastric cancer in the European prospective investigation into cancer and nutrition
- 2006
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Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755. ; 15:12, s. 2427-2434
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Tidskriftsartikel (refereegranskat)abstract
- Metabolizing enzymes, which often display genetic polymorphisms, are involved in the activation of compounds present in tobacco smoke that may be relevant to gastric carcinogenesis. We report the results of a study looking at the association between risk of gastric adenocarcinoma and polymorphisms in genes CYP1A1, CYP1A2, EPHX1, and GSTT1. A nested case-control study was carried out within the European Prospective Investigation into Cancer and Nutrition, developed in 10 European countries. The study includes 243 newly diagnosed cases of histologically confirmed gastric adenocarcinoma and 946 controls matched by center, age, sex, and date of blood collection. Genotypes were determined in nuclear DNA from WBCs. We found an increased risk of gastric cancer for homozygotes for C (histidine) variant in Y113H of EPHX1 (odds ratio, 1.91; 95% confidence interval, 1.19-3.07) compared with subjects with TC/TT. There was also a significant increased risk for smokers carrying at least one variant allele A in Ex7+129C > A (m4) of CYP1A1 and never smokers with null GSTT1 and allele A in the locus -3859G > A of CYP1A2. Most of these genes are involved in the activation and detoxification of polycyclic aromatic hydrocarbons, suggesting a potential role of these compounds in gastric carcinogenesis.
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