| 1. |
- Murphy, Neil, et al.
(författare)
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Circulating Levels of Insulin-like Growth Factor 1 and Insulin-like Growth Factor Binding Protein 3 Associate With Risk of Colorectal Cancer Based on Serologic and Mendelian Randomization Analyses
- 2020
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Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 158:5, s. 1300-1312.e20
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Human studies examining associations between circulating levels of insulin-like growth factor 1 (IGF1) and insulin-like growth factor binding protein 3 (IGFBP3) and colorectal cancer risk have reported inconsistent results. We conducted complementary serologic and Mendelian randomization (MR) analyses to determine whether alterations in circulating levels of IGF1 or IGFBP3 are associated with colorectal cancer development.Methods: Serum levels of IGF1 were measured in blood samples collected from 397,380 participants from the UK Biobank, from 2006 through 2010. Incident cancer cases and cancer cases recorded first in death certificates were identified through linkage to national cancer and death registries. Complete follow-up was available through March 31, 2016. For the MR analyses, we identified genetic variants associated with circulating levels of IGF1 and IGFBP3. The association of these genetic variants with colorectal cancer was examined with 2-sample MR methods using genome-wide association study consortia data (52,865 cases with colorectal cancer and 46,287 individuals without [controls])Results: After a median follow-up period of 7.1 years, 2665 cases of colorectal cancer were recorded. In a multivariable-adjusted model, circulating level of IGF1 associated with colorectal cancer risk (hazard ratio per 1 standard deviation increment of IGF1, 1.11; 95% confidence interval [CI] 1.05–1.17). Similar associations were found by sex, follow-up time, and tumor subsite. In the MR analyses, a 1 standard deviation increment in IGF1 level, predicted based on genetic factors, was associated with a higher risk of colorectal cancer risk (odds ratio 1.08; 95% CI 1.03–1.12; P = 3.3 × 10–4). Level of IGFBP3, predicted based on genetic factors, was associated with colorectal cancer risk (odds ratio per 1 standard deviation increment, 1.12; 95% CI 1.06–1.18; P = 4.2 × 10–5). Colorectal cancer risk was associated with only 1 variant in the IGFBP3 gene region (rs11977526), which also associated with anthropometric traits and circulating level of IGF2.Conclusions: In an analysis of blood samples from almost 400,000 participants in the UK Biobank, we found an association between circulating level of IGF1 and colorectal cancer. Using genetic data from 52,865 cases with colorectal cancer and 46,287 controls, a higher level of IGF1, determined by genetic factors, was associated with colorectal cancer. Further studies are needed to determine how this signaling pathway might contribute to colorectal carcinogenesis.
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| 2. |
- Aleksandrova, Krasimira, et al.
(författare)
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Combined impact of healthy lifestyle factors on colorectal cancer : a large European cohort study
- 2014
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Ingår i: BMC Medicine. - : BioMed Central. - 1741-7015. ; 12:1, s. 168-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Excess body weight, physical activity, smoking, alcohol consumption and certain dietary factors are individually related to colorectal cancer (CRC) risk; however, little is known about their joint effects. The aim of this study was to develop a healthy lifestyle index (HLI) composed of five potentially modifiable lifestyle factors - healthy weight, physical activity, non-smoking, limited alcohol consumption and a healthy diet, and to explore the association of this index with CRC incidence using data collected within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: In the EPIC cohort, a total of 347,237 men and women, 25- to 70-years old, provided dietary and lifestyle information at study baseline (1992 to 2000). Over a median follow-up time of 12 years, 3,759 incident CRC cases were identified. The association between a HLI and CRC risk was evaluated using Cox proportional hazards regression models and population attributable risks (PARs) have been calculated. RESULTS: After accounting for study centre, age, sex and education, compared with 0 or 1 healthy lifestyle factors, the hazard ratio (HR) for CRC was 0.87 (95% confidence interval (CI): 0.44 to 0.77) for two factors, 0.79 (95% CI: 0.70 to 0.89) for three factors, 0.66 (95% CI: 0.58 to 0.75) for four factors and 0.63 (95% CI: 0.54 to 0.74) for five factors; P-trend <0.0001. The associations were present for both colon and rectal cancers, HRs, 0.61 (95% CI: 0.50 to 0.74; P for trend <0.0001) for colon cancer and 0.68 (95% CI: 0.53 to 0.88; P-trend <0.0001) for rectal cancer, respectively (P-difference by cancer sub-site = 0.10). Overall, 16% of the new CRC cases (22% in men and 11% in women) were attributable to not adhering to a combination of all five healthy lifestyle behaviours included in the index. CONCLUSIONS: Combined lifestyle factors are associated with a lower incidence of CRC in European populations characterized by western lifestyles. Prevention strategies considering complex targeting of multiple lifestyle factors may provide practical means for improved CRC prevention.
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| 3. |
- Besevic, Jelena, et al.
(författare)
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Reproductive factors and epithelial ovarian cancer survival in the EPIC cohort study
- 2015
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Ingår i: British Journal of Cancer. - : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 113:11, s. 1622-1631
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Tidskriftsartikel (refereegranskat)abstract
- Background: Reproductive factors influence the risk of developing epithelial ovarian cancer (EOC), but little is known about their association with survival. We tested whether prediagnostic reproductive factors influenced EOC-specific survival among 1025 invasive EOC cases identified in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, which included 521 330 total participants (approximately 370 000 women) aged 25-70 years at recruitment from 1992 to 2000. Methods: Information on reproductive characteristics was collected at recruitment. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), and multivariable models were adjusted for age and year of diagnosis, body mass index, tumour stage, smoking status and stratified by study centre. Results: After a mean follow-up of 3.6 years (+/- 3.2 s.d.) following EOC diagnosis, 511 (49.9%) of the 1025 women died from EOC. We observed a suggestive survival advantage in menopausal hormone therapy (MHT) users (ever vs never use, HR = 0.80, 95% CI = 0.62-1.03) and a significant survival benefit in long-term MHT users (>= 5 years use vs never use, HR = 0.70, 95% CI = 0.50-0.99, P-trend = 0.04). We observed similar results for MHT use when restricting to serous cases. Other reproductive factors, including parity, breastfeeding, oral contraceptive use and age at menarche or menopause, were not associated with EOC-specific mortality risk. Conclusions: Further studies are warranted to investigate the possible improvement in EOC survival in MHT users.
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| 4. |
- Bradbury, Kathryn E., et al.
(författare)
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Circulating insulin-like growth factor I in relation to melanoma risk in the European prospective investigation into cancer and nutrition
- 2019
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 144:5, s. 957-966
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Tidskriftsartikel (refereegranskat)abstract
- Insulin-like growth factor-I (IGF-I) regulates cell proliferation and apoptosis, and is thought to play a role in tumour development. Previous prospective studies have shown that higher circulating concentrations of IGF-I are associated with a higher risk of cancers at specific sites, including breast and prostate. No prospective study has examined the association between circulating IGF-I concentrations and melanoma risk. A nested case-control study of 1,221 melanoma cases and 1,221 controls was performed in the European Prospective Investigation into Cancer and Nutrition cohort, a prospective cohort of 520,000 participants recruited from 10 European countries. Conditional logistic regression was used to estimate odds ratios (ORs) for incident melanoma in relation to circulating IGF-I concentrations, measured by immunoassay. Analyses were conditioned on the matching factors and further adjusted for age at blood collection, education, height, BMI, smoking status, alcohol intake, marital status, physical activity and in women only, use of menopausal hormone therapy. There was no significant association between circulating IGF-I concentration and melanoma risk (OR for highest vs lowest fifth = 0.93 [95% confidence interval [CI]: 0.71 to 1.22]). There was no significant heterogeneity in the association between IGF-I concentrations and melanoma risk when subdivided by gender, age at blood collection, BMI, height, age at diagnosis, time between blood collection and diagnosis, or by anatomical site or histological subtype of the tumour (Pheterogeneity≥0.078). We found no evidence for an association between circulating concentrations of IGF-I measured in adulthood and the risk of melanoma.
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| 5. |
- Merritt, Melissa A., et al.
(författare)
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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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Ingår i: Cancer Epidemiology. - : Elsevier BV. - 1877-7821 .- 1877-783X. ; 38:5, s. 528-537
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Tidskriftsartikel (refereegranskat)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.
(författare)
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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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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 24:2, s. 466-471
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Tidskriftsartikel (refereegranskat)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. |
- Schmidt, Julie A, et al.
(författare)
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Insulin-like growth factor-I and risk of differentiated thyroid carcinoma in the European Prospective Investigation into Cancer and Nutrition
- 2014
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 23:6, s. 976-985
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Tidskriftsartikel (refereegranskat)abstract
- Background: Little is known about the causes of thyroid cancer, but insulin-like growth factor-I (IGF-I) might play an important role in its development due to its mitogenic and anti-apoptotic properties. Methods: This study prospectively investigated the association between serum IGF-I concentrations and risk of differentiated thyroid carcinoma in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition. 345 incident cases of differentiated thyroid carcinoma were individually matched to 735 controls by study centre, sex, and age, date, time, and fasting status at blood collection, follow-up duration, and for women menopausal status, use of exogenous hormones, and phase of menstrual cycle at blood collection. Serum IGF-I concentrations were measured by immunoassay, and risk of differentiated thyroid cancer in relation to IGF-I concentration was estimated using conditional logistic regression. Results: There was a positive association between IGF-I concentrations and risk of differentiated thyroid carcinoma: the odds ratio for a doubling in IGF-I concentration was 1.48 (95% confidence interval: 1.06 - 2.08; ptrend = 0.02). The positive association with IGF-I was stable over time between blood collection and cancer diagnosis. Conclusion: These findings suggest that IGF-I concentrations may be positively associated with risk of differentiated thyroid carcinoma. Impact: This study provides the first prospective evidence of a potential association between circulating IGF-I concentrations and risk of differentiated thyroid carcinoma and may prompt the further investigations needed to confirm the association.
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| 8. |
- Terry, Kathryn L., et al.
(författare)
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A Prospective Evaluation of Early Detection Biomarkers for Ovarian Cancer in the European EPIC Cohort
- 2016
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Ingår i: Clinical Cancer Research. - : American Association for Cancer Research. - 1078-0432 .- 1557-3265. ; 22:18, s. 4664-4675
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: About 60% of ovarian cancers are diagnosed at late stage, when 5-year survival is less than 30% in contrast to 90% for local disease. This has prompted search for early detection biomarkers. For initial testing, specimens taken months or years before ovarian cancer diagnosis are the best source of information to evaluate earlydetection biomarkers. Here we evaluate the most promising ovarian cancer screening biomarkers in prospectively collected samples from the European Prospective Investigation into Cancer and Nutrition study. Experimental Design: We measured CA125, HE4, CA72.4, and CA15.3 in 810 invasive epithelial ovarian cancer cases and 1,939 controls. We calculated the sensitivity at 95% and 98% specificity as well as area under the receiver operator curve (C-statistic) for each marker individually and in combination. In addition, we evaluated marker performance by stage at diagnosis and time between blood draw and diagnosis. Results: We observed the best discrimination between cases and controls within 6 months of diagnosis for CA125 (C-statistic = 0.92), then HE4 (0.84), CA72.4 (0.77), and CA15.3 (0.73). Marker performance declined with longer time between blood draw and diagnosis and for earlier staged disease. However, assessment of discriminatory ability at early stage was limited by small numbers. Combinations of markers performed modestly, but significantly better than any single marker. Conclusions: CA125 remains the single best marker for the early detection of invasive epithelial ovarian cancer, but can be slightly improved by combining with other markers. Identifying novel markers for ovarian cancer will require studies including larger numbers of early-stage cases.
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| 9. |
- Fortner, Renee T., et al.
(författare)
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Reproductive and hormone-related risk factors for epithelial ovarian cancer by histologic pathways, invasiveness and histologic subtypes: Results from the EPIC cohort
- 2015
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 137:5, s. 1196-1208
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Tidskriftsartikel (refereegranskat)abstract
- Whether risk factors for epithelial ovarian cancer (EOC) differ by subtype (i.e., dualistic pathway of carcinogenesis, histologic subtype) is not well understood; however, data to date suggest risk factor differences. We examined associations between reproductive and hormone-related risk factors for EOC by subtype in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Among 334,126 women with data on reproductive and hormone-related risk factors (follow-up: 1992-2010), 1,245 incident cases of EOC with known histology and invasiveness were identified. Data on tumor histology, grade, and invasiveness, were available from cancer registries and pathology record review. We observed significant heterogeneity by the dualistic model (i.e., type I [low grade serous or endometrioid, mucinous, clear cell, malignant Brenner] vs. type II [high grade serous or endometrioid]) for full-term pregnancy (p(het)=0.02). Full-term pregnancy was more strongly inversely associated with type I than type II tumors (ever vs. never: type I: relative risk (RR) 0.47 [95% confidence interval (CI): 0.33-0.69]; type II, RR: 0.81 [0.61-1.06]). We observed no significant differences in risk in analyses by major histologic subtypes of invasive EOC (serous, mucinous, endometrioid, clear cell). None of the investigated factors were associated with borderline tumors. Established protective factors, including duration of oral contraceptive use and full term pregnancy, were consistently inversely associated with risk across histologic subtypes (e.g., ever full-term pregnancy: serous, RR: 0.73 [0.58-0.92]; mucinous, RR: 0.53 [0.30-0.95]; endometrioid, RR: 0.65 [0.40-1.06]; clear cell, RR: 0.34 [0.18-0.64]; p(het)=0.16). These results suggest limited heterogeneity between reproductive and hormone-related risk factors and EOC subtypes. What's new? Reproductive and hormone-related risk factors for epithelial ovarian cancer (EOC) have been extensively investigated. However, EOC is increasingly recognized as a heterogeneous disease and risk factor differences across EOC subtypes, as defined by the recently proposed dualistic pathway of ovarian carcinogenesis and histological characteristics, are not well understood. Here, the authors present a detailed prospective investigation on reproductive and hormone-related risk factors for borderline tumors and epithelial ovarian cancer by main histological subtypes and, for the first time, by the types defined by the dualistic pathway. The results suggest limited heterogeneity between reproductive and hormone-related risk factors and EOC subtypes.
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| 10. |
- Ose, Jennifer, et al.
(författare)
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Inflammatory markers and risk of epithelial ovarian cancer by tumor subtypes: the EPIC cohort.
- 2015
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Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755 .- 1055-9965. ; 24:6, s. 951-961
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Tidskriftsartikel (refereegranskat)abstract
- Evidence suggests an etiologic role for inflammation in ovarian carcinogenesis and heterogeneity between tumor subtypes and anthropometric indices. Prospective studies on circulating inflammatory markers and epithelial invasive ovarian cancer (EOC) have predominantly investigated overall risk; data characterizing risk by tumor characteristics (histology, grade, stage, dualistic model of ovarian carcinogenesis) and anthropometric indices are sparse.
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