| 21. |
- Companioni, Osmel, et al.
(författare)
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Polymorphisms of H. pylori signaling pathway genes and gastric cancer risk in the European EPIC-eurgast cohort
- 2014
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Ingår i: International Journal of Cancer. - : Wiley-Blackwell. - 0020-7136 .- 1097-0215. ; 134:1, s. 92-101
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Tidskriftsartikel (refereegranskat)abstract
- Helicobacter pylori is a recognized causal factor of noncardia gastric cancer (GC). Lipopolysaccaride and peptidoglycan of this bacterium are recognized by CD14, TLR4 and NOD2 human proteins, while NFKB1 activates the transcription of pro-inflammatory cytokines to elicit an immune response. SNPs in these genes have been associated with GC in different populations. We genotyped 30 SNPs of these genes, in 365 gastric adenocarcinomas and 1284 matched controls from the EPIC cohort. The association with GC and its histological and anatomical subtypes was analyzed by logistic regression and corrected for multiple comparisons. Using a log-additive model we found a significant association between SNPs in CD14, NOD2 and TLR4 with GC risk. However, after applying the multiple comparisons tests only the NOD2 region remained significant (p=0.009). Analysis according to anatomical subtypes revealed NOD2 and NFKB1 SNPs associated with noncardia GC and CD14 SNPs associated with cardia GC, while analysis according to histological subtypes showed that CD14 was associated with intestinal but not diffuse GC. The multiple comparisons tests confirmed the association of NOD2 with noncardia GC (p=0.0003) and CD14 with cardia GC (p=0.01). Haplotype analysis was in agreement with single SNP results for NOD2 and CD14 genes. From these results we conclude that genetic variation in NOD2 associates with noncardia GC while variation in CD14 is associated with cardia GC.
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| 22. |
- Companioni, Osmel, et al.
(författare)
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Polymorphisms of Helicobacter pylori signaling pathway genes and gastric cancer risk in the European Prospective Investigation into Cancer-Eurgast cohort
- 2014
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 134:1, s. 92-101
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Tidskriftsartikel (refereegranskat)abstract
- Helicobacter pylori is a recognized causal factor of noncardia gastric cancer (GC). Lipopolysaccharide and peptidoglycan of this bacterium are recognized by CD14, TLR4 and NOD2 human proteins, while NFKB1 activates the transcription of pro-inflammatory cytokines to elicit an immune response. Single nucleotide polymorphisms (SNPs) in these genes have been associated with GC in different populations. We genotyped 30 SNPs of these genes, in 365 gastric adenocarcinomas and 1,284 matched controls from the European Prospective Investigation into Cancer cohort. The association with GC and its histological and anatomical subtypes was analyzed by logistic regression and corrected for multiple comparisons. Using a log-additive model, we found a significant association between SNPs in CD14, NOD2 and TLR4 with GC risk. However, after applying the multiple comparisons tests only the NOD2 region remained significant (p=0.009). Analysis according to anatomical subtypes revealed NOD2 and NFKB1 SNPs associated with noncardia GC and CD14 SNPs associated with cardia GC, while analysis according to histological subtypes showed that CD14 was associated with intestinal but not diffuse GC. The multiple comparisons tests confirmed the association of NOD2 with noncardia GC (p=0.0003) and CD14 with cardia GC (p=0.01). Haplotype analysis was in agreement with single SNP results for NOD2 and CD14 genes. From these results, we conclude that genetic variation in NOD2 associates with noncardia GC while variation in CD14 is associated with cardia GC. What's new? Variations in immune genes appear to play an important role in determining susceptibility to gastric cancer linked to Helicobacter pylori colonization of gastric mucosa. However, little is known about the influence of variation on anatomical localization and histological subtype of this malignancy. The results of this study first confirm that NOD2 and CD14, which encode proteins that recognize H. pylori lipopolysaccharide and peptidoglycan, are significantly associated with gastric cancer risk and second indicate that NOD2 associates with noncardia and CD14 with cardia gastric cancer. The differential effects of variation on the anatomical localization of disease warrant further investigation.
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| 23. |
- Dik, Vincent K., et al.
(författare)
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Coffee and tea consumption, genotype- based CYP1A2 and NAT2 activity and colorectal cancer risk- Results from the EPIC cohort study
- 2014
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 135:2, s. 401-412
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Tidskriftsartikel (refereegranskat)abstract
- Coffee and tea contain numerous antimutagenic and antioxidant components and high levels of caffeine that may protect against colorectal cancer (CRC). We investigated the association between coffee and tea consumption and CRC risk and studied potential effect modification by CYP1A2 and NAT2 genotypes, enzymes involved in the metabolization of caffeine. Data from 477,071 participants (70.2% female) of the European Investigation into Cancer and Nutrition (EPIC) cohort study were analyzed. At baseline (1992-2000) habitual (total, caffeinated and decaffeinated) coffee and tea consumption was assessed with dietary questionnaires. Cox proportional hazards models were used to estimate adjusted hazard ratio's (HR) and 95% confidence intervals (95% CI). Potential effect modification by genotype-based CYP1A2 and NAT2 activity was studied in a nested case-control set of 1,252 cases and 2,175 controls. After a median follow-up of 11.6 years, 4,234 participants developed CRC (mean age 64.78.3 years). Total coffee consumption (high vs. non/low) was not associated with CRC risk (HR 1.06, 95% CI 0.95-1.18) or subsite cancers, and no significant associations were found for caffeinated (HR 1.10, 95% CI 0.97-1.26) and decaffeinated coffee (HR 0.96, 95% CI 0.84-1.11) and tea (HR 0.97, 95% CI 0.86-1.09). High coffee and tea consuming subjects with slow CYP1A2 or NAT2 activity had a similar CRC risk compared to non/low coffee and tea consuming subjects with a fast CYP1A2 or NAT2 activity, which suggests that caffeine metabolism does not affect the link between coffee and tea consumption and CRC risk. This study shows that coffee and tea consumption is not likely to be associated with overall CRC. What's new? Coffee and tea contain numerous compounds that may protect against colorectal cancer (CRC). In this study of more than 475,000 participants over more than a decade, the authors investigated whether coffee or tea consumption is associated with an altered risk of developing CRC. They also asked whether genetic variations in two enzymes involved in caffeine metabolism (CYP1A2 and NAT2) might affect this risk. They conclude that neither consumption patterns, nor genetic differences in caffeine metabolism, appear to have a significant impact on CRC risk.
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| 24. |
- Duell, Eric J, et al.
(författare)
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Alcohol consumption and gastric cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.
- 2011
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 94:5, s. 1266-75
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Gastric cancer (GC) is the second leading cause of cancer death worldwide. The association between alcohol consumption and GC has been investigated in numerous epidemiologic studies with inconsistent results. OBJECTIVE: We evaluated the association between alcohol consumption and GC risk. DESIGN: We conducted a prospective analysis in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, which included 444 cases of first primary gastric adenocarcinoma. HRs and 95% CIs for GC were estimated by using multivariable Cox proportional hazards regression for consumption of pure ethanol in grams per day, with stratification by smoking status, anatomic subsite (cardia, noncardia), and histologic subtype (diffuse, intestinal). In a subset of participants, results were further adjusted for baseline Helicobacter pylori serostatus. RESULTS: Heavy (compared with very light) alcohol consumption (≥60 compared with 0.1-4.9 g/d) at baseline was positively associated with GC risk (HR: 1.65; 95% CI: 1.06, 2.58), whereas lower consumption amounts (<60 g/d) were not. When we analyzed GC risk by type of alcoholic beverage, there was a positive association for beer (≥30 g/d; HR: 1.75; 95% CI: 1.13, 2.73) but not for wine or liquor. Associations were primarily observed at the highest amounts of drinking in men and limited to noncardia subsite and intestinal histology; no statistically significant linear dose-response trends with GC risk were observed. CONCLUSION: Heavy (but not light or moderate) consumption of alcohol at baseline (mainly from beer) is associated with intestinal-type noncardia GC risk in men from the EPIC cohort.
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| 25. |
- Duell, Eric J, et al.
(författare)
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Menstrual and reproductive factors, exogenous hormone use, and gastric cancer risk in a cohort of women from the European Prospective Investigation Into Cancer and Nutrition
- 2010
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Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 172:12, s. 1384-1393
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Tidskriftsartikel (refereegranskat)abstract
- The worldwide incidence of gastric adenocarcinoma (GC) is lower in women than in men. Furthermore, cancer patients treated with estrogens have been reported to have a lower subsequent risk of GC. The authors conducted a prospective analysis of menstrual and reproductive factors, exogenous hormone use, and GC in 335,216 women from the European Prospective Investigation Into Cancer and Nutrition, a cohort study of individuals aged 35-70 years from 10 European countries. After a mean follow-up of 8.7 years (through 2004), 181 women for whom complete exposure data were available developed GC. Adjusted hazard ratios and 95% confidence intervals were estimated using Cox proportional hazards models. All statistical tests were 2-sided. Women who had ovariectomy had a 79% increased risk of GC (based on 25 cases) compared with women who did not (hazard ratio = 1.79, 95% confidence interval: 1.15, 2.78). Total cumulative years of menstrual cycling was inversely associated with GC risk (fifth vs. first quintile: hazard ratio = 0.55, 95% confidence interval: 0.31, 0.98; P(trend) = 0.06). No other reproductive factors analyzed were associated with risk of GC. The results of this analysis provide some support for the hypothesis that endogenous ovarian sex hormones lower GC incidence in women.
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| 26. |
- 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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| 27. |
- Espinosa-Parrilla, Yolanda, et al.
(författare)
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Genetic association of gastric cancer with miRNA clusters including the cancer-related genes MIR29, MIR25, MIR93 and MIR106: Results from the EPIC-EURGAST study
- 2014
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 135:9, s. 2065-2076
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Tidskriftsartikel (refereegranskat)abstract
- MicroRNAs (miRNAs) are post-transcriptional gene regulators involved in a wide range of biological processes including tumorigenesis. Deregulation of miRNA pathways has been associated with cancer but the contribution of their genetic variability to this disorder is poorly known. We analyzed the genetic association of gastric cancer (GC) and its anatomical and histological subtypes, with 133 single-nucleotide polymorphisms (SNPs) tagging 15 isolated miRNAs and 24 miRNA clusters potentially involved in cancer, in 365 GC cases and 1,284 matched controls within the European Prospective Investigation into Cancer and Nutrition cohort. Various SNPs were associated with GC under the log-additive model. Furthermore, several of these miRNAs passed the gene-based permutation test when analyzed according to GC subtypes: three tagSNPs of the miR-29a/miR-29b-1 cluster were associated with diffuse subtype (minimum p-value=1.7 x 10(-4); odds ratio, OR=1.72; 95% confidence interval, CI=1.30-2.28), two tagSNPs of the miR-25/miR-93/miR-106b cluster were associated with cardia GC (minimum p-value=5.38 x 10(-3); OR=0.56, 95% CI=0.37-0.86) and one tagSNP of the miR-363/miR-92a-2/miR-19b-2/miR-20b/miR-18b/miR-106a cluster was associated with noncardia GC (minimum p-value=5.40 x 10(-3); OR=1.41, 95% CI=1.12-1.78). Some functionally validated target genes of these miRNAs are implicated in cancer-related processes such as methylation (DNMT3A, DNMT3B), cell cycle (E2F1, CDKN1A, CDKN1C), apoptosis (BCL2L11, MCL1), angiogenesis (VEGFA) and progression (PIK3R1, MYCN). Furthermore, we identified genetic interactions between variants tagging these miRNAs and variants in their validated target genes. Deregulation of the expression of these miRNAs in GC also supports our findings, altogether suggesting for the fist time that genetic variation in MIR29, MIR25, MIR93 and MIR106b may have a critical role in genetic susceptibility to GC and could contribute to the molecular mechanisms of gastric carcinogenesis.
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| 28. |
- Eussen, Simone JPM, et al.
(författare)
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Plasma folate, related genetic variants, and colorectal cancer risk in EPIC
- 2010
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 19:5, s. 1328-1340
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Tidskriftsartikel (refereegranskat)abstract
- Findings of the present study tend to weaken the evidence that folate plays an important role in CRC carcinogenesis. However, larger sample sizes are needed to adequately address potential gene-environment interactions.
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| 29. |
- Fedirko, Veronika, et al.
(författare)
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Prediagnostic 25-Hydroxyvitamin D, VDR and CASR polymorphisms, and survival in patients with colorectal cancer in Western European populations
- 2012
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 21:4, s. 582-593
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Tidskriftsartikel (refereegranskat)abstract
- Background: Individuals with higher blood 25-hydroxyvitamin D [25(OH)D] levels have a lower risk of developing colorectal cancer (CRC), but the influence of 25(OH)D on mortality after CRC diagnosis is unknown.Methods: The association between prediagnostic 25(OH)D levels and CRC-specific (N ¼ 444) and overall mortality (N ¼ 541) was prospectively examined among 1,202 participants diagnosed with CRC between 1992 and 2003 in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.Multivariable Cox proportional hazards models were used to calculate HRs and corresponding 95% CIs according to 25(OH)D quintiles and genetic variation within the VDR and CASR genes. Potential dietary, lifestyle, and metabolic effect modifiers were also investigated.Results: There were 541 deaths, 444 (82%) due to CRC. Mean follow-up was 73 months. In multivariable analysis, higher 25(OH)D levels were associated with a statistically significant reduction in CRC-specific (Ptrend ¼ 0.04) and overall mortality (Ptrend ¼ 0.01). Participants with 25(OH)D levels in the highest quintile had an adjusted HR of 0.69 (95% CI: 0.50–0.93) for CRC-specific mortality and 0.67 (95% CI: 0.50–0.88) for overall mortality, compared with the lowest quintile. Except for a possible interaction by prediagnostic dietary calcium intake (Pinteraction ¼ 0.01), no other potential modifying factors related to CRC survival were noted. The VDR (FokI and BsmI) and CASR (rs1801725) genotypes were not associated with survival.Conclusions: High prediagnostic 25(OH)D levels are associated with improved survival of patients with CRC. Impact: Our findings may stimulate further research directed at investigating the effects of blood vitamin D levels before, at, and after CRC diagnosis on outcomes in CRC patients.
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| 30. |
- Fedirko, Veronika, et al.
(författare)
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Prediagnostic circulating parathyroid hormone concentration and colorectal cancer in the European Prospective Investigation into Cancer and Nutrition cohort
- 2011
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 20:5, s. 767-778
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Parathyroid hormone (PTH) has been proposed to play a promoting role in carcinogenesis. However, no epidemiologic studies have yet directly investigated its role in colorectal cancer (CRC). METHODS: A case-control study nested within the European Prospective Investigation into Cancer and Nutrition cohort was conducted with 1,214 incident, sporadic CRC cases matched to 1,214 controls. Circulating prediagnostic PTH and 25-hydroxy vitamin D [25(OH)D] concentrations were measured by enzyme-linked immunosorbent assays. Detailed dietary and lifestyle questionnaire data were collected at baseline. Multivariable conditional logistic regression was used to estimate the incidence rate ratio (RR) with 95% confidence intervals (95% CI) for the association between circulating PTH and CRC risk. RESULTS: In multivariate analyses [including adjustment for 25(OH)D concentration] with a priori defined cutoff points, high levels of serum PTH (≥65 ng/L) compared with medium PTH levels of 30-65 ng/L were associated with increased CRC risk (RR = 1.41, 95% CI: 1.03-1.93). In analyses by sex, the CRC risk was 1.77 (95% CI: 1.14-2.75) and 1.15 (95% CI: 0.73-1.84) in men and women, respectively (P(heterogeneity) = 0.01). In subgroup analyses by anatomical subsite, the risk for colon cancer was RR = 1.56, 95% CI: 1.03-2.34, and for rectal cancer RR = 1.20, 95% CI: 0.72-2.01 (P(heterogeneity) = 0.21). Effect modification by various risk factors was examined. CONCLUSIONS: The results of this study suggest that high serum PTH levels may be associated with incident, sporadic CRC in Western European populations, and in particular among men. IMPACT: To our knowledge, this is the first study on PTH and CRC. The role of PTH in carcinogenesis needs to be further investigated.
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