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- 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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| 2. |
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| 3. |
- 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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| 4. |
- Roswall, Nina, et al.
(författare)
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Consumption of predefined 'Nordic' dietary items in ten European countries : an investigation in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort
- 2014
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Ingår i: Public Health Nutrition. - : Cambridge University Press. - 1368-9800 .- 1475-2727. ; 17:12, s. 2650-2659
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Health-beneficial effects of adhering to a healthy Nordic diet index have been suggested. However, it has not been examined to what extent the included dietary components are exclusively related to the Nordic countries or if they are part of other European diets as well, suggesting a broader preventive potential. The present study describes the intake of seven a priori defined healthy food items (apples/pears, berries, cabbages, dark bread, shellfish, fish and root vegetables) across ten countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) and examines their consumption across Europe. DESIGN: Cross-sectional study. A 24 h dietary recall was administered through a software program containing country-specific recipes. Sex-specific mean food intake was calculated for each centre/country, as well as percentage of overall food groups consumed as healthy Nordic food items. All analyses were weighted by day and season of data collection. SETTING: Multi-centre, European study. SUBJECTS: Persons (n 36 970) aged 35-74 years, constituting a random sample of 519 978 EPIC participants. RESULTS: The highest intakes of the included diet components were: cabbages and berries in Central Europe; apples/pears in Southern Europe; dark bread in Norway, Denmark and Greece; fish in Southern and Northern countries; shellfish in Spain; and root vegetables in Northern and Central Europe. Large inter-centre variation, however, existed in some countries. CONCLUSIONS: Dark bread, root vegetables and fish are strongly related to a Nordic dietary tradition. Apples/pears, berries, cabbages, fish, shellfish and root vegetables are broadly consumed in Europe, and may thus be included in regional public health campaigns.
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| 5. |
- Tikk, Kaja, et al.
(författare)
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Circulating prolactin and breast cancer risk among pre- and postmenopausal women in the EPIC cohort
- 2014
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Ingår i: Annals of Oncology. - : Oxford University Press. - 0923-7534 .- 1569-8041. ; 25:7, s. 1422-1428
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Experimental and epidemiological evidence suggests that prolactin might play a role in the etiology of breast cancer. We analyzed the relationship of pre-diagnostic circulating prolactin levels with the risk of breast cancer by menopausal status, use of postmenopausal hormone replacement therapy (HRT) at blood donation, and by estrogen and progesterone receptor-status of the breast tumors. METHODS: Conditional logistic regression was used to analyze the data from a case-control study nested within the prospective European EPIC cohort, including 2250 invasive breast cancer and their matched control subjects. RESULTS: Statistically significant heterogeneity in the association of prolactin levels with breast cancer risk between women who were either pre- or postmenopausal at the time of blood donation was observed (Phet=0.04). Higher serum levels of prolactin were associated with significant increase in risk of breast cancer among postmenopausal women (ORQ4-Q1=1.29 [95%CI 1.05-1.58], Ptrend=0.09); however this increase in risk seemed to be confined to women who used postmenopausal HRT at blood donation (ORQ4-Q1=1.45 [95%CI 1.08-1.95], Ptrend=0.01), whereas no statistically significant association was found for the non-users of HRT (ORQ4-Q1 =1.11 [95%CI 0.83-1.49], Ptrend=0.80) (Phet=0.08). Among premenopausal women, a statistically non-significant inverse association was observed (ORQ4-Q1 =0.70 [95%CI 0.48-1.03], Ptrend=0.16). There was no heterogeneity in the prolactin-breast cancer association by hormone receptor status of the tumor. CONCLUSION: Our study indicates that higher circulating levels of prolactin among the postmenopausal HRT users at baseline may be associated with increased breast cancer risk.
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| 6. |
- Tikk, Kaja, et al.
(författare)
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Prolactin Determinants in Healthy Women : A Large Cross-Sectional Study within the EPIC Cohort
- 2014
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 23:11, s. 2532-2542
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Tidskriftsartikel (refereegranskat)abstract
- Background: Experimental and epidemiologic data suggest that higher circulating prolactin is associated with breast cancer risk; however, how various risk factors for breast cancer influence prolactin levels in healthy women is not clear. Methods: We analyzed cross-sectional associations between several suggested reproductive and lifestyle risk factors for breast cancer and circulating prolactin among pre- and postmenopausal women, taking into account the use of current postmenopausal hormone therapy, among 2,560 controls from a breast cancer nested case-control study within the EPIC cohort. Results: Adjusted geometric mean prolactin levels were significantly higher among premenopausal women, and among postmenopausal women using hormone therapy compared with nonusers (8.2, 7.0, and 6.3 ng/mL, respectively; P-cat = <0.0001). Furthermore, prolactin levels were significantly higher among users of combined estrogen-progestin hormone therapy compared with users of estrogen-alone hormone therapy (6.66 vs. 5.90 ng/mL; P-cat = 0.001). Prolactin levels were lower among parous women compared with nulliparous women (8.61 vs. 10.95 ng/mL; P-cat = 0.0002, premenopausal women); the magnitude of this difference depended on the number of full-term pregnancies (22.1% lower, >= 3 vs. 1 pregnancy, P-trend = 0.01). Results for parity were similar but lower in magnitude among postmenopausal women. Prolactin did not vary by other studied factors, with the exception of lower levels among postmenopausal smokers compared with never smokers. Conclusions: Our study shows that current hormone therapy use, especially the use of combined hormone therapy, is associated with higher circulating prolactin levels in postmenopausal women, and confirms prior findings of lower circulating prolactin in parous women. Impact: Our study extends the knowledge linking various breast cancer risk factors with circulating prolactin.
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