| 1. |
- Baltar, Valéria Troncoso, et al.
(author)
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A structural equation modelling approach to explore the role of B vitamins and immune markers in lung cancer risk
- 2013
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In: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 28:8, s. 677-688
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Journal article (peer-reviewed)abstract
- The one-carbon metabolism (OCM) is considered key in maintaining DNA integrity and regulating gene expression, and may be involved in the process of carcinogenesis. Several B-vitamins and amino acids have been implicated in lung cancer risk, via the OCM directly as well as immune system activation. However it is unclear whether these factors act independently or through complex mechanisms. The current study applies structural equations modelling (SEM) to further disentangle the mechanisms involved in lung carcinogenesis. SEM allows simultaneous estimation of linear relations where a variable can be the outcome in one equation and the predictor in another, as well as allowing estimation using latent variables (factors estimated by correlation matrix). A large number of biomarkers have been analysed from 891 lung cancer cases and 1,747 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Four putative mechanisms in the OCM and immunity were investigated in relation to lung cancer risk: methionine-homocysteine metabolism, folate cycle, transsulfuration, and mechanisms involved in inflammation and immune activation, all adjusted for tobacco exposure. The hypothesized SEM model confirmed a direct and protective effect for factors representing methionine-homocysteine metabolism (p = 0.020) and immune activation (p = 0.021), and an indirect protective effect of folate cycle (p = 0.019), after adjustment for tobacco smoking. In conclusion, our results show that in the investigation of the involvement of the OCM, the folate cycle and immune system in lung carcinogenesis, it is important to consider complex pathways (by applying SEM) rather than the effects of single vitamins or nutrients (e.g. using traditional multiple regression). In our study SEM were able to suggest a greater role of the methionine-homocysteine metabolism and immune activation over other potential mechanisms.
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| 2. |
- Dossus, Laure, et al.
(author)
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Reproductive risk factors and endometrial cancer : the European prospective investigation into cancer and nutrition
- 2010
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 127:2, s. 442-451
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Journal article (peer-reviewed)abstract
- Endometrial cancer risk has been associated with reproductive factors (age at menarche, age at menopause, parity, age at first and last birth, time since last birth and use of oral contraceptives (OCs)]. However, these factors are closely interrelated and whether they act independently still requires clarification. We conducted a study to examine the association of menstrual and reproductive variables with the risk of endometrial cancer among the European Prospective Investigation into Cancer and Nutrition (EPIC). Among the 302,618 women eligible for the study, 1,017 incident endometrial cancer cases were identified. A reduction in endometrial cancer risk was observed in women with late menarche, early menopause, past OC use, high parity and a shorter time since last full-term pregnancy (FTP). No association was observed for duration of breast feeding after adjustment for number of FTP or for abortion (spontaneous or induced). After mutual adjustment, late age at menarche, early age at menopause and duration of OC use showed similar risk reductions of 7-8% per year of menstrual life, whereas the decreased risk associated with cumulative duration of FTPs was stronger (22% per year). In conclusion, our findings confirmed a reduction in risk of endometrial cancer with factors associated with a lower cumulative exposure to estrogen and/or higher exposure to progesterone, such as increasing number of FTPs and shorter menstrual lifespan and, therefore, support an important role of hormonal mechanisms in endometrial carcinogenesis.
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| 3. |
- Gu, Fangyi, et al.
(author)
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Eighteen insulin-like growth factor pathway genes, circulating levels of IGF-I and its binding protein, and risk of prostate and breast cancer
- 2010
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In: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 19:11, s. 2877-2887
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Journal article (peer-reviewed)abstract
- Background: Circulating levels of insulin-like growth factor I (IGF-I) and its main binding protein, IGF binding protein 3 (IGFBP-3), have been associated with risk of several types of cancer. Heritable factors explain up to 60% of the variation in IGF-I and IGFBP-3 in studies of adult twins.Methods: We systematically examined common genetic variation in 18 genes in the IGF signaling pathway for associations with circulating levels of IGF-I and IGFBP-3. A total of 302 single nucleotide polymorphisms (SNP) were genotyped in >5,500 Caucasian men and 5,500 Caucasian women from the Breast and Prostate Cancer Cohort Consortium.Results: After adjusting for multiple testing, SNPs in the IGF1 and SSTR5 genes were significantly associated with circulating IGF-I (P < 2.1 × 10−4); SNPs in the IGFBP3 and IGFALS genes were significantly associated with circulating IGFBP-3. Multi-SNP models explained R2 = 0.62% of the variation in circulating IGF-I and 3.9% of the variation in circulating IGFBP-3. We saw no significant association between these multi-SNP predictors of circulating IGF-I or IGFBP-3 and risk of prostate or breast cancers.Conclusion: Common genetic variation in the IGF1 and SSTR5 genes seems to influence circulating IGF-I levels, and variation in IGFBP3 and IGFALS seems to influence circulating IGFBP-3. However, these variants explain only a small percentage of the variation in circulating IGF-I and IGFBP-3 in Caucasian men and women.Impact: Further studies are needed to explore contributions from other genetic factors such as rare variants in these genes and variation outside of these genes.
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| 4. |
- Hosnijeh, Fatemeh Saberi, et al.
(author)
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Prediagnostic telomere length and risk of B-cell lymphoma-Results from the EPIC cohort study
- 2014
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 135:12, s. 2910-2917
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Journal article (peer-reviewed)abstract
- Recent epidemiological investigations have reported on the association between telomere length (TL) and a number of malignancies, including B-cell lymphoma (BCL). The reported results for BCLs are however inconsistent. We carried out a nested case-control study to determine whether TL is associated with future risk of BCL. Using quantitative polymerase chain reaction, the relative TL (i.e. the ratio of telomere repeat copy number to single gene copy number) was measured in mononuclear cell DNA of prediagnostic peripheral blood samples of 464 lymphoma cases and 464 matched controls (median time between blood collection and diagnosis, 4.6 years). Conditional logistic regression was used to analyze the association between TL and the risk of developing lymphoma and histologic subtypes. TL was significantly longer in cases compared to controls (p 5 0.01). Multivariable models showed a significantly increased risk of BCL [odds ratio (OR) = 1.66, 1.80 and 3.20 for quartiles 2-4, respectively, p-trend = 0.001], diffuse large B-cell lymphoma (DLBCL) (OR = 1.20, 2.48 and 2.36 for quartiles 2-4, respectively, p-trend = 0.03) and follicular lymphoma (FL) (OR = 1.39, 1.90 and 2.69 for quartiles 2-4, respectively, p-trend = 0.02) with increasing TL. This study suggests an association between longer leucocyte TL and increased risk of BCL which was most pronounced for DLBCL and FL.
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| 5. |
- Merritt, Melissa A., et al.
(author)
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Dietary fat intake and risk of epithelial ovarian cancer in the European Prospective Investigation into Cancer and Nutrition
- 2014
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In: Cancer Epidemiology. - : Elsevier BV. - 1877-7821 .- 1877-783X. ; 38:5, s. 528-537
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Journal article (peer-reviewed)abstract
- There are inconsistent and limited data available to assess the relationship between fat intake and risk of epithelial ovarian cancer (EOC). We examined the consumption of total fat, fat sources and fat subtypes in relation to risk of EOC and its major histologic subtypes in the European Prospective Investigation into Cancer and Nutrition which includes incident invasive (n = 1095) and borderline (n = 96) EOC. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). In multivariate models, we observed no association with consumption of total fat, animal or plant fat, saturated fat, cholesterol, monounsaturated fat, or fatty fish and risk of invasive EOC. There was, however, an increased risk of invasive EOC in the highest category of intake (Quartile 4 vs. Quartile 1) of polyunsaturated fat (HR = 1.22, 95% CI = 1.02-1.48, P-trend = 0.02). We did not observe heterogeneity in the risk associations in comparisons of serous and endometrioid histologic subtypes. This study does not support an etiological role for total fat intake in relation to EOC risk; however, based on observations of a positive association between intake of polyunsaturated fat and invasive EOC risk in the current and previous studies, this fat subtype warrants further investigation to determine its potential role in EOC development.
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| 6. |
- Merritt, Melissa A., et al.
(author)
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Investigation of Dietary Factors and Endometrial Cancer Risk Using a Nutrient-wide Association Study Approach in the EPIC and Nurses' Health Study (NHS) and NHSII
- 2015
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In: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 24:2, s. 466-471
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Journal article (peer-reviewed)abstract
- Data on the role of dietary factors in endometrial cancer development are limited and inconsistent. We applied a "nutrient-wide association study" approach to systematically evaluate dietary risk associations for endometrial cancer while controlling for multiple hypothesis tests using the false discovery rate (FDR) and validating the results in an independent cohort. We evaluated endometrial cancer risk associations for dietary intake of 84 foods and nutrients based on dietary questionnaires in three prospective studies, the European Prospective Investigation into Cancer and Nutrition (EPIC; N = 1,303 cases) followed by validation of nine foods/nutrients (FDR <= 0.10) in the Nurses' Health Studies (NHS/NHSII; N = 1,531 cases). Cox regression models were used to estimate HRs and 95% confidence intervals (CI). In multivariate adjusted comparisons of the extreme categories of intake at baseline, coffee was inversely associated with endometrial cancer risk (EPIC, median intake 750 g/day vs. 8.6; HR, 0.81; 95% CI, 0.68-0.97, P-trend = 0.09; NHS/NHSII, median intake 1067 g/day vs. none; HR, 0.82; 95% CI, 0.70-0.96, P-trend = 0.04). Eight other dietary factors that were associated with endometrial cancer risk in the EPIC study (total fat, monounsaturated fat, carbohydrates, phosphorus, butter, yogurt, cheese, and potatoes) were not confirmed in the NHS/NHSII. Our findings suggest that coffee intake may be inversely associated with endometrial cancer risk. Further data are needed to confirm these findings and to examine the mechanisms linking coffee intake to endometrial cancer risk to develop improved prevention strategies. (C)2015 AACR.
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| 7. |
- Obon-Santacana, Mireia, et al.
(author)
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Dietary Intake of Acrylamide and Epithelial Ovarian Cancer Risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) Cohort
- 2015
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In: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 24:1, s. 291-297
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Journal article (peer-reviewed)abstract
- Acrylamide, classified in 1994 by the International Agency for Research on Cancer (IARC) as "probably carcinogenic" to humans, was discovered in 2002 in some heat-treated, carbohydrate-rich foods. The association between dietary acrylamide intake and epithelial ovarian cancer risk (EOC) has been previously studied in one case-control and three prospective cohort studies which obtained inconsistent results and could not further examine histologic subtypes other than serous EOC. The present study was carried out in the European Prospective Investigation into Cancer and Nutrition (EPIC) subcohort of women (n = 325,006). Multivariate Cox proportional hazards models were used to assess the association between questionnaire-based acrylamide intake and EOC risk. Acrylamide was energy-adjusted using the residual method and was evaluated both as a continuous variable (per 10 mu g/d) and in quintiles; when subgroups by histologic EOC subtypes were analyzed, acrylamide intake was evaluated in quartiles. During a mean follow-up of 11 years, 1,191 incident EOC cases were diagnosed. At baseline, the median acrylamide intake in EPIC was 21.3 mu g/d. No associations and no evidence for a dose-response were observed between energy-adjusted acrylamide intake and EOC risk (HR10 mu(g/d), 1.02; 95% CI, 0.96-1.09; HRQ5vsQ1, 0.97; 95% CI, 0.76-1.23). No differences were seen when invasive EOC subtypes (582 serous, 118 endometrioid, and 79 mucinous tumors) were analyzed separately. This study did not provide evidence that acrylamide intake, based on food intake questionnaires, was associated with risk for EOC in EPIC. Additional studies with more reliable estimates of exposure based on biomarkers may be needed.
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| 8. |
- Ose, Jennifer, et al.
(author)
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Endogenous androgens and risk of epithelial invasive ovarian cancer by tumor characteristics in the European Prospective Investigation into Cancer and Nutrition
- 2014
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 136:2, s. 399-410
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Journal article (peer-reviewed)abstract
- The role of endogenous androgens and sex hormone-binding globulin (SHBG) in ovarian carcinogenesis is poorly understood. Epithelial invasive ovarian cancer (EOC) is a heterogeneous disease and there are no prospective data on endogenous androgens and EOC risk by tumor characteristics (histology, grade, stage) or the dualistic model of ovarian carcinogenesis (i.e. type I vs. type II, leading to less or more aggressive tumors). We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort evaluating androgens and SHBG and invasive EOC risk by tumor characteristics. Female participants who provided a blood sample and were not using exogenous hormones at blood donation were eligible (n = 183,257). A total of 565 eligible women developed EOC; two controls (n = 1,097) were matched per case. We used multivariable conditional logistic regression models. We observed no association between androgens, SHBG and EOC overall. A doubling of androstenedione reduced risk of serous carcinomas by 21% (odds ratio (OR)log2=0.79, 95% confidence interval [CI]=[0.64-0.97]). Moreover, associations differed for low-grade and high-grade carcinomas, with positive associations for low-grade and inverse associations for high-grade carcinomas (e.g. androstenedione: low grade: ORlog2=1.99 [0.98-4.06]; high grade: ORlog2=0.75 [0.61-0.93], p(het)0.01), similar associations were observed for type I/II tumors. This is the first prospective study to evaluate androgens, SHBG and EOC risk by tumor characteristics and type I/II status. Our findings support a possible role of androgens in ovarian carcinogenesis. Additional studies exploring this association are needed. What's new? There appear to be several types of epithelial invasive ovarian cancer (EOC), and hormone-related risk factors are poorly understood. In this study, the authors found that the impact of endogenous androgens on the risk of developing EOC differed depending upon tumor characteristics. Androgen concentrations were positively associated with the risk of low-grade and type-I carcinomas, but the study found an inverse association for high-grade tumors. These findings support a possible role for androgens in ovarian carcinogenesis, and emphasize the need for additional research.
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| 9. |
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| 10. |
- Tikk, Kaja, et al.
(author)
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Circulating prolactin and in situ breast cancer risk in the European EPIC cohort : a case-control study
- 2015
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In: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 17
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Journal article (peer-reviewed)abstract
- Introduction The relationship between circulating prolactin and invasive breast cancer has been investigated previously, but the association between prolactin levels and in situ breast cancer risk has received less attention.Methods We analysed the relationship between pre-diagnostic prolactin levels and the risk of in situ breast cancer overall, and by menopausal status and use of postmenopausal hormone therapy (HT) at blood donation. Conditional logistic regression was used to assess this association in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, including 307 in situ breast cancer cases and their matched control subjects.Results We found a significant positive association between higher circulating prolactin levels and risk of in situ breast cancer among all women [pre-and postmenopausal combined, ORlog2 = 1.35 (95% CI 1.04-1.76), P-trend = 0.03]. No statistically significant heterogeneity was found between prolactin levels and in situ cancer risk by menopausal status (P-het = 0.98) or baseline HT use (P-het = 0.20), although the observed association was more pronounced among postmenopausal women using HT compared to non-users (P-trend = 0.06 vs P-trend = 0.35). In subgroup analyses, the observed positive association was strongest in women diagnosed with in situ breast tumors <4 years compared to >= 4 years after blood donation (P-trend = 0.01 vs P-trend = 0.63; P-het = 0.04) and among nulliparous women compared to parous women (P-trend = 0.03 vs P-trend = 0.15; P-het = 0.07).Conclusions Our data extends prior research linking prolactin and invasive breast cancer to the outcome of in situ breast tumours and shows that higher circulating prolactin is associated with increased risk of in situ breast cancer.The relationship between circulating prolactin and invasive breast cancer has been investigated previously, but the association between prolactin levels and in situ breast cancer risk has received less attention.
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