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Lukanova, Annekatrin
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Publications (10 of 18) Show all publications
Romieu, I., Scoccianti, C., Chajes, V., de Batlle, J., Biessy, C., Dossus, L., . . . Riboli, E. (2015). Alcohol intake and breast cancer in the European Prospective investigation into Cancer and Nutrition: Short title. International Journal of Cancer, 137(8), 1921-1930
Open this publication in new window or tab >>Alcohol intake and breast cancer in the European Prospective investigation into Cancer and Nutrition: Short title
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2015 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 137, no 8, p. 1921-1930Article in journal (Refereed) Published
Abstract [en]

Alcohol intake has been associated to breast cancer in pre and postmenopausal women; however results are inconclusive regarding tumor hormonal receptor status, and potential modifying factors like age at start drinking. Therefore, we investigated the relation between alcohol intake and the risk of breast cancer using prospective observational data from the European Prospective Investigation into Cancer and Nutrition (EPIC). Up to 334,850 women, aged 35-70 years at baseline, were recruited in ten European countries and followed up an average of 11 years. Alcohol intake at baseline and average lifetime alcohol intake were calculated from country-specific dietary and lifestyle questionnaires. The study outcomes were the Hazard ratios (HR) of developing breast cancer according to hormonal receptor status. During 3,670,439 person-years, 11,576 incident breast cancer cases were diagnosed. Alcohol intake was significantly related to breast cancer risk, for each 10 g/day increase in alcohol intake the HR increased by 4.2% (95% CI: 2.7-5.8%). Taking 0 to 5 g/day as reference, alcohol intake of >5 to 15 g/day was related to a 5.9% increase in breast cancer risk (95% CI: 1-11%). Significant increasing trends were observed between alcohol intake and ER+/PR+, ER-/PR-, HER2- and ER-/PR-HER2- tumors. Breast cancer risk was stronger among women who started drinking prior to first full-time pregnancy. Overall, our results confirm the association between alcohol intake and both hormone receptor positive and hormone receptor negative breast tumors, suggesting that timing of exposure to alcohol drinking may affect the risk. Therefore, women should be advised to control their alcohol consumption. What's new? Although it is now established that alcohol consumption increases breast cancer risk, many questions remain. Using a prospective study design with 11,576 incident breast cancer cases across 10 European countries, the authors confirmed the increased risk of alcohol on breast cancer development. They further show that women who started drinking before their first full-term pregnancy have a higher risk than women who started afterwards. These effects were observed in hormone-receptor positive and -negative tumors pointing to non-hormonal pathways that need to be further investigated.

Keywords
Alcohol consumption, Breast cancer, Prospective study
National Category
Public Health, Global Health, Social Medicine and Epidemiology Nutrition and Dietetics
Identifiers
urn:nbn:se:umu:diva-102899 (URN)10.1002/ijc.29469 (DOI)000359350600019 ()25677034 (PubMedID)
Available from: 2015-05-09 Created: 2015-05-09 Last updated: 2018-06-07Bibliographically approved
Brand, J. S., Onland-Moret, N. C., Eijkemans, M. J., Tjönneland, A., Roswall, N., Overvad, K., . . . van der Schouw, Y. T. (2015). Diabetes and onset of natural menopause: results from the European Prospective Investigation into Cancer and Nutrition. Human Reproduction, 30(6), 1491-1498
Open this publication in new window or tab >>Diabetes and onset of natural menopause: results from the European Prospective Investigation into Cancer and Nutrition
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2015 (English)In: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 30, no 6, p. 1491-1498Article in journal (Refereed) Published
Abstract [en]

STUDY QUESTION: Do women who have diabetes before menopause have their menopause at an earlier age compared with women without diabetes? SUMMARY ANSWER: Although there was no overall association between diabetes and age at menopause, our study suggests that early-onset diabetes may accelerate menopause. WHAT IS KNOWN ALREADY: Today, more women of childbearing age are being diagnosed with diabetes, but little is known about the impact of diabetes on reproductive health. STUDY DESIGN, SIZE, DURATION: We investigated the impact of diabetes on age at natural menopause (ANM) in 258 898 women from the European Prospective Investigation into Cancer and Nutrition (EPIC), enrolled between 1992 and 2000. PARTICIPANTS/MATERIALS, SETTING, METHODS: Determinant and outcome information was obtained through questionnaires. Time-dependent Cox regression analyses were used to estimate the associations of diabetes and age at diabetes diagnosis with ANM, stratified by center and adjusted for age, smoking, reproductive and diabetes risk factors and with age from birth to menopause or censoring as the underlying time scale. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, no association between diabetes and ANM was found (hazard ratio (HR) = 0.94; 95% confidence interval (CI) 0.89-1.01). However, women with diabetes before the age of 20 years had an earlier menopause (10-20 years: HR = 1.43; 95% CI 1.02-2.01, <10 years: HR = 1.59; 95% CI 1.03-2.43) compared with non-diabetic women, whereas women with diabetes at age 50 years and older had a later menopause (HR = 0.81; 95% CI 0.70-0.95). None of the other age groups were associated with ANM. LIMITATIONS, REASONS FOR CAUTION: Strengths of the study include the large sample size and the broad set of potential confounders measured. However, results may have been underestimated due to survival bias. We cannot be sure about the sequence of the events in women with a late age at diabetes, as both events then occur in a short period. We could not distinguish between type 1 and type 2 diabetes. WIDER IMPLICATIONS OF THE FINDINGS: Based on the literature, an accelerating effect of early-onset diabetes on ANM might be plausible. A delaying effect of late-onset diabetes on ANM has not been reported before, and is not in agreement with recent studies suggesting the opposite association.

Place, publisher, year, edition, pages
Oxford University Press, 2015
Keywords
age at natural menopause, diabetes, time-dependent modeling, cox proportional hazards analyses
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-106797 (URN)10.1093/humrep/dev054 (DOI)000358015200024 ()25779698 (PubMedID)
Available from: 2015-08-14 Created: 2015-08-07 Last updated: 2018-06-07Bibliographically approved
Brand, J. S., Onland-Moret, N. C., Eijkemans, M. J., Tjonneland, A., Roswall, N., Overvad, K., . . . van der Schouw, Y. T. (2015). Diabetes and Onset of Natural Menopause: Results From the European Prospective Investigation Into Cancer and Nutrition EDITORIAL COMMENT. Obstetrical and Gynecological Survey, 70(8), 507-508
Open this publication in new window or tab >>Diabetes and Onset of Natural Menopause: Results From the European Prospective Investigation Into Cancer and Nutrition EDITORIAL COMMENT
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2015 (English)In: Obstetrical and Gynecological Survey, ISSN 0029-7828, E-ISSN 1533-9866, Vol. 70, no 8, p. 507-508Article in journal, Editorial material (Other academic) Published
Abstract [en]

The age at natural menopause (ANM) in the Western world ranges from 40 to 60 years, with an average onset of 51 years. The exact mechanisms underlying the timing of ANM are not completely understood. Both genetic and environmental factors are involved. The best-established environmental factor affecting ANM is smoking; menopause occurs 1 to 2 years earlier in smokers. In addition to genetic and environmental factors, chronic metabolic diseases may influence ANM. Some evidence suggests that diabetes may accelerate menopausal onset. With more women of childbearing age receiving a diagnosis of diabetes, it is important to examine the impact of diabetes on reproductive health. This study was designed to determine whether ANM occurs at an earlier age among women who have diabetes before menopause than in women without diabetes. Data were obtained from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, a large multicenter prospective cohort study investigating the relationship between diet, lifestyle, and genetic factors and the incidence of cancer and other chronic diseases. A cohort of 519,978 men and women, mostly aged 27 to 70 years, were recruited primarily from the general population between 1992 and 2000. A total of 367,331 women participated in the EPIC study. After exclusions, 258,898 of these women met study inclusion criteria. Diabetes status at baseline and menopausal age were based on self-report and were obtained through questionnaires. Participants were asked if they had ever been diagnosed with diabetes and if so at what age. Associations of diabetes and age at diabetes diagnosis with ANM were estimated using time-dependent Cox regression analyses, with stratification by center and adjustments for age, smoking, reproductive, and known diabetes risk factors including smoking and with age from birth to menopause or censoring as the underlying time scale. Overall, there was no statistically significant lower risk of becoming menopausal among women with diabetes than women with no diabetes; the hazard ratio (HR) was 0.94, with a 95% confidence interval (CI) of 0.89 to 1.01. However, compared with women with no diabetes, women with diabetes before the age of 20 years had an earlier menopause (10-20 years [HR, 1.43; 95% CI, 1.02-2.01] and <10 years [HR, 1.59; 95% CI, 1.03-2.43]), whereas women with diabetes at age 50 years or older had a later menopause (HR, 0.81; 95% CI, 0.70-0.95). No association with ANM was found for diabetes onset between the ages 20 and 50 years. Strengths of the study include its large sample size and the measurement of a broad set of potential confounders. However, there were several limitations. First, results may have been underestimated because of survival bias. Second, the sequence of menopause and diabetes in women with a late age at diabetes is uncertain, as both events occur in a short period, and both diabetes and menopause status were based on self-report, not verified by medical records. Third, no distinction was made between types 1 and 2 diabetes. Although there is no overall association between diabetes and age at menopause, the data suggest that early-onset diabetes may accelerate menopause. The delaying effect of late-onset diabetes on ANM is not in agreement with other studies suggesting the opposite association.

National Category
Obstetrics, Gynecology and Reproductive Medicine Endocrinology and Diabetes
Identifiers
urn:nbn:se:umu:diva-109459 (URN)10.1097/OGX.0000000000000235 (DOI)000360143200016 ()
Available from: 2015-10-08 Created: 2015-09-28 Last updated: 2018-06-07Bibliographically approved
Tsilidis, K. K., Allen, N. E., Appleby, P. N., Rohrmann, S., Nöthlings, U., Arriola, L., . . . Key, T. J. (2015). Diabetes mellitus and risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition. International Journal of Cancer, 136(2), 372-381
Open this publication in new window or tab >>Diabetes mellitus and risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition
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2015 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 136, no 2, p. 372-381Article in journal (Refereed) Published
Abstract [en]

The current epidemiologic evidence suggests that men with type 2 diabetes mellitus may be at lower risk of developing prostate cancer, but little is known about its association with stage and grade of the disease. The association between self-reported diabetes mellitus at recruitment and risk of prostate cancer was examined in the European Prospective Investigation into Cancer and Nutrition (EPIC). Among 139,131 eligible men, 4,531 were diagnosed with prostate cancer over an average follow-up of 12 years. Multivariable hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models stratified by EPIC-participating center and age at recruitment, and adjusted for education, smoking status, body mass index, waist circumference, and physical activity. In a subset of men without prostate cancer, the cross-sectional association between circulating concentrations of androgens and insulin-like growth factor proteins with diabetes status was also investigated using linear regression models. Compared to men with no diabetes, men with diabetes had a 26% lower risk of prostate cancer (HR, 0.74; 95% CI, 0.63-0.86). There was no evidence that the association differed by stage (p-heterogeneity, 0.19) or grade (p-heterogeneity, 0.48) of the disease, although the numbers were small in some disease subgroups. In a subset of 626 men with hormone measurements, circulating concentrations of androstenedione, total testosterone and insulin-like growth factor binding protein-three were lower in men with diabetes compared to men without diabetes. This large European study has confirmed an inverse association between self-reported diabetes mellitus and subsequent risk of prostate cancer.

What's new? Emerging evidence suggests that men with type 2 diabetes are at lower risk to develop prostate cancer. Using data obtained within the European Prospective Investigation into Cancer and Nutrition (EPIC), the authors show that the prostate cancer risk was, indeed, reduced by 26% in men with type 2 diabetes but no association with cancer stage or grade was observed. In a subset of men for whom data on circulating hormones were available, levels of androstenedione, total testosterone and insulin-like growth factor binding protein-three were lower in those with diabetes as compared to those without diabetes, giving clues to how having diabetes could affect prostate cancer development.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2015
Keywords
type 2 diabetes, prostate cancer, cohort study, androgens, insulin-like growth factor proteins
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-97270 (URN)10.1002/ijc.28989 (DOI)000344596600015 ()
Available from: 2014-12-12 Created: 2014-12-12 Last updated: 2018-06-07Bibliographically approved
Schock, H., Lundin, E., Vääräsmäki, M., Grankvist, K., Fry, A., Dorgan, J. F., . . . Lukanova, A. (2014). Anti-Mullerian hormone and risk of invasive serous ovarian cancer. Cancer Causes and Control, 25(5), 583-589
Open this publication in new window or tab >>Anti-Mullerian hormone and risk of invasive serous ovarian cancer
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2014 (English)In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 25, no 5, p. 583-589Article in journal (Refereed) Published
Abstract [en]

Epithelial ovarian cancers either arise directly from Mullerian-type epithelium or acquire Mullerian characteristics in the course of neoplastic transformation. The anti-Mullerian hormone (AMH) causes regression of Mullerian structures during fetal development in males and has been shown to inhibit the growth of epithelial ovarian cancer. Therefore, we hypothesized that pre-diagnostic serum concentrations of AMH are inversely associated with risk of invasive serous ovarian cancer. A case-control study (107 cases, 208 controls) was nested within the population-based Finnish Maternity Cohort (1986-2007). The sample donated during the first trimester of the last pregnancy preceding cancer diagnosis of the case subjects was selected for the study. For each case, two controls, matched on age and date at sampling, as well as parity at sampling and at cancer diagnosis were selected. AMH was measured by a second-generation AMH ELISA. Conditional logistic regression was used to compute odds ratios (OR) and 95 % confidence intervals (CI) for invasive serous ovarian cancer associated with AMH concentrations. Overall AMH concentrations were not associated with risk of invasive serous ovarian cancer (OR 0.93; 95 % CI 0.49-1.77 for top vs. bottom tertile, P (trend) = 0.83). In women older than the median age at sampling (32.7 years), a doubling of AMH was associated with decreased risk (OR 0.69; 95 % CI 0.49-0.96), whereas an increased risk (OR 1.64; 95 % CI 1.06-2.54) was observed in younger women, P (homogeneity) = 0.002. In this first prospective investigation, risk of invasive serous ovarian cancer was not associated with pre-diagnostic AMH concentrations overall; however, the association may depend on age at AMH measurement.

Place, publisher, year, edition, pages
Springer, 2014
Keywords
Anti-Mullerian hormone, Ovarian neoplasms, Pregnancy, Case-control studies, Prospective studies
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-88941 (URN)10.1007/s10552-014-0363-9 (DOI)000334409500005 ()
Available from: 2014-05-22 Created: 2014-05-19 Last updated: 2018-06-07Bibliographically approved
Aleksandrova, K., Jenab, M., Bueno-de-Mesquita, H. B., Fedirko, V., Kaaks, R., Lukanova, A., . . . Boeing, H. (2014). Biomarker patterns of inflammatory and metabolic pathways are associated with risk of colorectal cancer: results from the European Prospective Investigation into Cancer and Nutrition (EPIC). European Journal of Epidemiology, 29(4), 261-275
Open this publication in new window or tab >>Biomarker patterns of inflammatory and metabolic pathways are associated with risk of colorectal cancer: results from the European Prospective Investigation into Cancer and Nutrition (EPIC)
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2014 (English)In: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 29, no 4, p. 261-275Article in journal (Refereed) Published
Abstract [en]

A number of biomarkers of inflammatory and metabolic pathways are individually related to higher risk of colorectal cancer (CRC); however, the association between biomarker patterns and CRC incidence has not been previously evaluated. Our study investigates the association of biomarker patterns with CRC in a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC). During median follow-up time of 7.0 (3.7-9.4) years, 1,260 incident CRC cases occurred and were matched to 1,260 controls using risk-set sampling. Pre-diagnostic measurements of C-peptide, glycated hemoglobin, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), C-reactive protein (CRP), reactive oxygen metabolites (ROM), insulin-like growth factor 1, adiponectin, leptin and soluble leptin receptor (sOB-R) were used to derive biomarker patterns from principal component analysis (PCA). The relation with CRC incidence was assessed using conditional logistic regression models. We identified four biomarker patterns 'HDL-C/Adiponectin fractions', 'ROM/CRP', 'TG/C-peptide' and 'leptin/sOB-R' to explain 60 % of the overall biomarker variance. In multivariable-adjusted logistic regression, the 'HDL-C/Adiponectin fractions', 'ROM/CRP' and 'leptin/sOB-R' patterns were associated with CRC risk [for the highest quartile vs the lowest, incidence rate ratio (IRR) = 0.69, 95 % CI 0.51-0.93, P-trend = 0.01; IRR = 1.70, 95 % CI 1.30-2.23, P-trend = 0.002; and IRR = 0.79, 95 % CI 0.58-1.07; P-trend = 0.05, respectively]. In contrast, the 'TG/C-peptide' pattern was not associated with CRC risk (IRR = 0.75, 95 % CI 0.56-1.00, P-trend = 0.24). After cases within the first 2 follow-up years were excluded, the 'ROM/CRP' pattern was no longer associated with CRC risk, suggesting potential influence of preclinical disease on these associations. By application of PCA, the study identified 'HDL-C/Adiponectin fractions', 'ROM/CRP' and 'leptin/sOB-R' as biomarker patterns representing potentially important pathways for CRC development.

Keywords
Colorectal cancer, Biomarker patterns, Inflammatory and metabolic pathways, Principal component analysis, European Prospective Investigation into Cancer and Nutrition (EPIC)
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-90866 (URN)10.1007/s10654-014-9901-8 (DOI)000336801600005 ()
Available from: 2014-07-08 Created: 2014-07-01 Last updated: 2018-06-07Bibliographically approved
Duarte-Salles, T., Fedirko, V., Stepien, M., Trichopoulou, A., Bamia, C., Lagiou, P., . . . Jenab, M. (2014). Dairy products and risk of hepatocellular carcinoma: the European Prospective Investigation into Cancer and Nutrition. International Journal of Cancer, 135(7), 1662-1672
Open this publication in new window or tab >>Dairy products and risk of hepatocellular carcinoma: the European Prospective Investigation into Cancer and Nutrition
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2014 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 135, no 7, p. 1662-1672Article in journal (Refereed) Published
Abstract [en]

Intake of dairy products has been associated with risk of some cancers, but findings are often inconsistent and information on hepatocellular carcinoma (HCC) risk is limited, particularly from prospective settings. The aim of our study was to investigate the association between consumption of total and specific dairy products (milk/cheese/yogurt) and their components (calcium/vitamin D/fats/protein), with first incident HCC (N(cases) = 191) in the European Prospective Investigation into Cancer and Nutrition cohort, including a nested case-control subset (N(cases) = 122) with the assessment of hepatitis B virus/hepatitis C virus infections status, liver damage and circulating insulin-like growth factor (IGF)-I levels. For cohort analyses, multivariable-adjusted Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI). For nested case-control analyses, conditional logistic regression was used to calculate odds ratios and 95% CI. A total of 477,206 participants were followed-up for an average of 11 years (person-years follow-up = 5,415,385). In the cohort study, a significant positive HCC risk association was observed for total dairy products (highest vs. lowest tertile, HR = 1.66, 95% CI: 1.13-2.43; p(trend) = 0.012), milk (HR = 1.51, 95% CI: 1.02-2.24; p(trend) = 0.049), and cheese (HR = 1.56, 95% CI: 1.02-2.38; p(trend) = 0.101), but not yogurt (HR = 0.94, 95% CI: 0.65-1.35). Dietary calcium, vitamin D, fat and protein from dairy sources were associated with increased HCC risk, whereas the same nutrients from nondairy sources showed inverse or null associations. In the nested case-control study, similar results were observed among hepatitis-free individuals. Results from this large prospective cohort study suggest that higher consumption of dairy products, particularly milk and cheese, may be associated with increased HCC risk. Validation of these findings in other populations is necessary. Potential biologic mechanisms require further exploration.

National Category
Nutrition and Dietetics Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-95216 (URN)10.1002/ijc.28812 (DOI)000340520800019 ()24615266 (PubMedID)
Available from: 2014-10-24 Created: 2014-10-24 Last updated: 2018-06-07Bibliographically approved
Toriola, A. T., Tolockiene, E., Schock, H., Surcel, H.-M., Zeleniuch-Jacquotte, A., Wadell, G., . . . Lukanova, A. (2014). Free beta- human chorionic gonadotropin, total human chorionic gonadotropin and maternal risk of breast cancer. Future Oncology, 10(3), 377-384
Open this publication in new window or tab >>Free beta- human chorionic gonadotropin, total human chorionic gonadotropin and maternal risk of breast cancer
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2014 (English)In: Future Oncology, ISSN 1479-6694, E-ISSN 1744-8301, Vol. 10, no 3, p. 377-384Article in journal (Refereed) Published
Abstract [en]

Background: We investigated whether the free -human chorionic gonadotropin (free -hCG) would provide additional information to that provided by total hCG alone and thus be useful in future epidemiological studies relating hCG to maternal breast cancer risk. Materials & methods: Cases (n = 159) and controls (n = 286) were a subset of our previous study within the Northern Sweden Maternity Cohort on total hCG during primiparous pregnancy and breast cancer risk. Results: The associations between total hCG (hazard ratio: 0.79; 95% CI: 0.49-1.27), free -hCG (hazard ratio: 0.85; 95% CI: 0.33-2.18) and maternal risk of breast cancer were very similar in all analyses and mutual adjustment for either one had minor effects on the risk estimates. Conclusion: In the absence of a reliable assay on intact hCG, total hCG alone can be used in epidemiological studies investigating hCG and breast cancer risk, as free -hCG does not appear to provide any additional information.

Keywords
breast cancer, free -human chorionic gonadotropin, human chorionic gonadotropin, nested case-control study, pregnancy
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-90464 (URN)10.2217/FON.13.208 (DOI)000331698600011 ()
Available from: 2014-07-07 Created: 2014-06-23 Last updated: 2018-06-07Bibliographically approved
Aleksandrova, K., Boeing, H., Nöthlings, U., Jenab, M., Fedirko, V., Kaaks, R., . . . Pischon, T. (2014). Inflammatory and metabolic biomarkers and risk of liver and bilary tract cancer. Hepatology, 60(3), 858-871
Open this publication in new window or tab >>Inflammatory and metabolic biomarkers and risk of liver and bilary tract cancer
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2014 (English)In: Hepatology, ISSN 0270-9139, E-ISSN 1527-3350, Vol. 60, no 3, p. 858-871Article in journal (Refereed) Published
Abstract [en]

Obesity and associated metabolic disorders have been implicated in liver carcinogenesis; however there is little data on the role of obesity-related biomarkers on liver cancer risk. We studied prospectively the association of inflammatory and metabolic biomarkers with risks of hepatocellular carcinoma (HCC), intra-hepatic bile duct (IBD) and gallbladder and bilary tract cancers outside of the liver (GBTC) in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC). Over an average of 7.7 years, 296 participants developed HCC (n=125), GBTC (n=137) or IBD (n=34). Using risk set sampling, controls were selected in a 2:1 ratio and matched for recruitment center, age, sex, fasting status, time of blood collection. Baseline serum concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), C-peptide, total, high-molecular-weight (HMW) adiponectin, leptin, fetuin-a, and glutamatdehydrogenase (GLDH) were measured and incidence rate ratios (IRRs) and 95% confidence intervals (CI-s) estimated using conditional logistic regression. After adjustment for lifestyle factors, diabetes, hepatitis infection and adiposity measures, higher concentrations of CRP, IL-6, C-peptide and non-HMW adiponectin were associated with higher risk of HCC (IRR per doubling of concentrations = 1.22; 95%CI = 1.02-1.46, P=0.03; 1.90; 95%CI = 1.30-2.77, P=0.001; 2.25; 95%CI = 1.43-3.54, P=0.0005 and 2.09; 95%CI = 1.19-3.67, P=0.01, respectively). CRP was associated also with risk of GBTC (IRR = 1.22; 95%CI = 1.05-1.42, P=0.01). GLDH was associated with risks of HCC (IRR = 1.62; 95%CI = 1.25-2.11, P=0.0003) and IBD (IRR = 10.5; 95%CI = 2.20-50.90, P=0.003). The continuous net reclassification index was 0.63 for CRP, IL-6, C-peptide and non-HMW adiponectin, and 0.46 for GLDH indicating good predictive ability of these biomarkers. Conclusion: Elevated levels of biomarkers of inflammation and hyperinsulinemia are associated with a higher risk of HCC, independent of obesity and established liver cancer risk factors.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2014
Keywords
liver cancer, biomarkers, hepatocellular carcinoma, bile duct cancer, inflammation, hyperinsulinemia
National Category
Cancer and Oncology Gastroenterology and Hepatology
Research subject
Medicine
Identifiers
urn:nbn:se:umu:diva-85156 (URN)10.1002/hep.27016 (DOI)000341239200014 ()24443059 (PubMedID)
Available from: 2014-01-28 Created: 2014-01-28 Last updated: 2018-06-08Bibliographically approved
Kaaks, R., Johnson, T., Tikk, K., Sookthai, D., Tjønneland, A., Roswall, N., . . . Lukanova, A. (2014). Insulin-like growth factor I and risk of breast cancer by age and hormone receptor status: A prospective study within the EPIC cohort. International Journal of Cancer, 134(11), 2683-2690
Open this publication in new window or tab >>Insulin-like growth factor I and risk of breast cancer by age and hormone receptor status: A prospective study within the EPIC cohort
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2014 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 134, no 11, p. 2683-2690Article in journal (Refereed) Published
Abstract [en]

Experimental evidence shows cross-talk in mammary cells between estrogen, insulin-like growth factor I (IGF-I) and their respective receptors and possible synergistic effects of estrogen receptor (ER) activation and increased IGF-I signaling with regard to breast tumor development, and epidemiological evidence suggests that circulating IGF-I levels may be related more to the risk of ER-positive than ER-negative breast cancer. Using a case–control study nested within the prospective European EPIC cohort (938 breast cancer cases and 1,394 matched control subjects), we analyzed the relationships of prediagnostic serum IGF-I levels with the risk of estrogen and progesterone receptor-positive and -negative breast tumors. IGF-I levels were positively associated with the risk of ER+ breast tumors overall (pre- and postmenopausal women combined, odds ratio (OR)Q4-Q1 = 1.41 [95% confidence interval (CI) 1.01–1.98] for the highest vs. lowest quartile; OR = 1.17 [95% CI 1.04–1.33] per 1-standard deviation (SD) increase in IGF-I, ptrend = 0.01) and among women who were diagnosed with breast cancer at 50 years or older (ORQ3-Q1 = 1.38 [95% CI 1.01–1.89]; OR = 1.19 [95% CI 1.04–1.36] per 1-SD increase in IGF-I, ptrend = 0.01) but not with receptor-positive disease diagnosed at an earlier age. No statistically significant associations were observed for ER− breast tumors overall and by age at diagnosis. Tests for heterogeneity by receptor status of the tumor were not statistically significant, except for women diagnosed with breast cancer at 50 years or older (phet = 0.03 for ER+/PR+ vs. ER−/PR− disease). Our data add to a global body of evidence indicating that higher circulating IGF-I levels may increase risk specifically of receptor-positive, but not receptor-negative, breast cancer diagnosed at 50 years or older.

Keywords
breast cancer, estrogen receptor, insulin-like growth factor I, prospective cohort, European Prospective Investigation into Cancer and Nutrition
National Category
Surgery
Identifiers
urn:nbn:se:umu:diva-88180 (URN)10.1002/ijc.28589 (DOI)000332801700017 ()24248481 (PubMedID)
Available from: 2014-04-24 Created: 2014-04-24 Last updated: 2018-06-07Bibliographically approved
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