| 1. |
- Alcala, Karine, et al.
(författare)
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The relationship between blood pressure and risk of renal cell carcinoma
- 2022
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Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 1464-3685 .- 0300-5771. ; 51:4, s. 1317-1327
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The relation between blood pressure and kidney cancer risk is well established but complex and different study designs have reported discrepant findings on the relative importance of diastolic blood pressure (DBP) and systolic blood pressure (SBP). In this study, we sought to describe the temporal relation between diastolic and SBP with renal cell carcinoma (RCC) risk in detail.METHODS: Our study involved two prospective cohorts: the European Prospective Investigation into Cancer and Nutrition study and UK Biobank, including >700 000 participants and 1692 incident RCC cases. Risk analyses were conducted using flexible parametric survival models for DBP and SBP both separately as well as with mutuality adjustment and then adjustment for extended risk factors. We also carried out univariable and multivariable Mendelian randomization (MR) analyses (DBP: ninstruments = 251, SBP: ninstruments = 213) to complement the analyses of measured DBP and SBP.RESULTS: In the univariable analysis, we observed clear positive associations with RCC risk for both diastolic and SBP when measured ≥5 years before diagnosis and suggestive evidence for a stronger risk association in the year leading up to diagnosis. In mutually adjusted analysis, the long-term risk association of DBP remained, with a hazard ratio (HR) per standard deviation increment 10 years before diagnosis (HR10y) of 1.20 (95% CI: 1.10-1.30), whereas the association of SBP was attenuated (HR10y: 1.00, 95% CI: 0.91-1.10). In the complementary multivariable MR analysis, we observed an odds ratio for a 1-SD increment (ORsd) of 1.34 (95% CI: 1.08-1.67) for genetically predicted DBP and 0.70 (95% CI: 0.56-0.88) for genetically predicted SBP.CONCLUSION: The results of this observational and MR study are consistent with an important role of DBP in RCC aetiology. The relation between SBP and RCC risk was less clear but does not appear to be independent of DBP.
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| 2. |
- Castro-Espin, Carlota, et al.
(författare)
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Dietary patterns related to biological mechanisms and survival after breast cancer diagnosis : results from a cohort study
- 2023
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Ingår i: British Journal of Cancer. - : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 128, s. 1301-1310
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Tidskriftsartikel (refereegranskat)abstract
- Background: Inflammatory, insulin and oestrogenic pathways have been linked to breast cancer (BC). We aimed to examine the relationship between pre-diagnostic dietary patterns related to these mechanisms and BC survival.Methods: The diabetes risk reduction diet (DRRD), inflammatory score of diet (ISD) and oestrogen-related dietary pattern (ERDP) were calculated using dietary data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Cox proportional hazards models were used to assess associations between dietary patterns and overall mortality and competing risk models for associations with BC-specific mortality.Results: We included 13,270 BC cases with a mean follow-up after diagnosis of 8.6 years, representing 2340 total deaths, including 1475 BC deaths. Higher adherence to the DRRD score was associated with lower overall mortality (HR1–SD 0.92; 95%CI 0.87–0.96). Greater adherence to pro-inflammatory diets was borderline associated with 6% higher mortality HR1–SD 1.06; 95%CI 1.00–1.12. No significant association with the oestrogen-related dietary pattern was observed. None of the dietary patterns were associated with BC-specific mortality.Conclusions: Greater adherence to an anti-diabetic and anti-inflammatory diet prior to diagnosis is associated with lower overall mortality among BC survivors. Long-term adherence to these dietary patterns could be a means to improve the prognosis of BC survivors.
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| 3. |
- Christakoudi, Sofia, et al.
(författare)
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A Body Shape Index (ABSI) achieves better mortality risk stratification than alternative indices of abdominal obesity : results from a large European cohort
- 2020
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Abdominal and general adiposity are independently associated with mortality, but there is no consensus on how best to assess abdominal adiposity. We compared the ability of alternative waist indices to complement body mass index (BMI) when assessing all-cause mortality. We used data from 352,985 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) and Cox proportional hazards models adjusted for other risk factors. During a mean follow-up of 16.1 years, 38,178 participants died. Combining in one model BMI and a strongly correlated waist index altered the association patterns with mortality, to a predominantly negative association for BMI and a stronger positive association for the waist index, while combining BMI with the uncorrelated A Body Shape Index (ABSI) preserved the association patterns. Sex-specific cohort-wide quartiles of waist indices correlated with BMI could not separate high-risk from low-risk individuals within underweight (BMI<18.5 kg/m(2)) or obese (BMI30 kg/m(2)) categories, while the highest quartile of ABSI separated 18-39% of the individuals within each BMI category, which had 22-55% higher risk of death. In conclusion, only a waist index independent of BMI by design, such as ABSI, complements BMI and enables efficient risk stratification, which could facilitate personalisation of screening, treatment and monitoring.
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| 4. |
- Christakoudi, Sofia, et al.
(författare)
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A body shape index (ABSI) is associated inversely with post-menopausal progesterone-receptor-negative breast cancer risk in a large European cohort
- 2023
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Ingår i: BMC Cancer. - 1471-2407. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Associations of body shape with breast cancer risk, independent of body size, are unclear because waist and hip circumferences are correlated strongly positively with body mass index (BMI). Methods: We evaluated body shape with the allometric “a body shape index” (ABSI) and hip index (HI), which compare waist and hip circumferences, correspondingly, among individuals with the same weight and height. We examined associations of ABSI, HI, and BMI (per one standard deviation increment) with breast cancer overall, and according to menopausal status at baseline, age at diagnosis, and oestrogen and progesterone receptor status (ER+/-PR+/-) in multivariable Cox proportional hazards models using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Results: During a mean follow-up of 14.0 years, 9011 incident breast cancers were diagnosed among 218,276 women. Although there was little evidence for association of ABSI with breast cancer overall (hazard ratio HR = 0.984; 95% confidence interval: 0.961–1.007), we found borderline inverse associations for post-menopausal women (HR = 0.971; 0.942-1.000; n = 5268 cases) and breast cancers diagnosed at age ≥ 55 years (HR = 0.976; 0.951–1.002; n = 7043) and clear inverse associations for ER + PR- subtypes (HR = 0.894; 0.822–0.971; n = 726) and ER-PR- subtypes (HR = 0.906; 0.835–0.983 n = 759). There were no material associations with HI. BMI was associated strongly positively with breast cancer overall (HR = 1.074; 1.049–1.098), for post-menopausal women (HR = 1.117; 1.085–1.150), for cancers diagnosed at age ≥ 55 years (HR = 1.104; 1.076–1.132), and for ER + PR + subtypes (HR = 1.122; 1.080–1.165; n = 3101), but not for PR- subtypes. Conclusions: In the EPIC cohort, abdominal obesity evaluated with ABSI was not associated with breast cancer risk overall but was associated inversely with the risk of post-menopausal PR- breast cancer. Our findings require validation in other cohorts and with a larger number of PR- breast cancer cases.
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| 5. |
- Christakoudi, Sofia, et al.
(författare)
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Blood pressure and risk of cancer in the European Prospective Investigation into Cancer and Nutrition
- 2020
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 146:10, s. 2680-2693
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Tidskriftsartikel (refereegranskat)abstract
- Several studies have reported associations of hypertension with cancer, but not all results were conclusive. We examined the association of systolic (SBP) and diastolic (DBP) blood pressure with the development of incident cancer at all anatomical sites in the European Prospective Investigation into Cancer and Nutrition (EPIC). Hazard ratios (HRs) (95% confidence intervals) were estimated using multivariable Cox proportional hazards models, stratified by EPIC-participating center and age at recruitment, and adjusted for sex, education, smoking, body mass index, physical activity, diabetes and dietary (in women also reproductive) factors. The study included 307,318 men and women, with an average follow-up of 13.7 (standard deviation 4.4) years and 39,298 incident cancers. We confirmed the expected positive association with renal cell carcinoma: HR = 1.12 (1.08-1.17) per 10 mm Hg higher SBP and HR = 1.23 (1.14-1.32) for DBP. We additionally found positive associations for esophageal squamous cell carcinoma (SCC): HR = 1.16 (1.07-1.26) (SBP), HR = 1.31 (1.13-1.51) (DBP), weaker for head and neck cancers: HR = 1.08 (1.04-1.12) (SBP), HR = 1.09 (1.01-1.17) (DBP) and, similarly, for skin SCC, colon cancer, postmenopausal breast cancer and uterine adenocarcinoma (AC), but not for esophageal AC, lung SCC, lung AC or uterine endometroid cancer. We observed weak inverse associations of SBP with cervical SCC: HR = 0.91 (0.82-1.00) and lymphomas: HR = 0.97 (0.93-1.00). There were no consistent associations with cancers in other locations. Our results are largely compatible with published studies and support weak associations of blood pressure with cancers in specific locations and morphologies.
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| 6. |
- Christakoudi, Sofia, et al.
(författare)
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Development and validation of the first consensus gene-expression signature of operational tolerance in kidney transplantation, incorporating adjustment for immunosuppressive drug therapy
- 2020
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Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 58
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Tidskriftsartikel (refereegranskat)abstract
- Background: Kidney transplant recipients (KTRs) with "operational tolerance" (OT) maintain a functioning graft without immunosuppressive (IS) drugs, thus avoiding treatment complications. Nevertheless, IS drugs can influence gene-expression signatures aiming to identify OT among treated KTRs. Methods: We compared five published signatures of OT in peripheral blood samples from 18 tolerant, 183 stable, and 34 chronic rejector KTRs, using gene-expression levels with and without adjustment for IS drugs and regularised logistic regression. Findings: IS drugs explained up to 50% of the variability in gene-expression and 20-30% of the variability in the probability of OT predicted by signatures without drug adjustment. We present a parsimonious consensus gene-set to identify OT, derived from joint analysis of IS-drug-adjusted expression of five published signature gene-sets. This signature, including CD40, CTLA4, HSD11B1, IGKV4-1, MZB1, NR3C2, and RAB40C genes, showed an area under the curve 0.92 (95% confidence interval 0.88-0.94) in cross-validation and 0.97 (0.93-1.00) in six months follow-up samples. Interpretation: We advocate including adjustment for IS drug therapy in the development stage of gene-expression signatures of OT to reduce the risk of capturing features of treatment, which could be lost following IS drug minimisation or withdrawal. Our signature, however, would require further validation in an independent dataset and a biomarker-led trial. (c) 2020 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license. (http://creativecommons.org/licenses/by/4.0/)
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| 7. |
- Christakoudi, Sofia, et al.
(författare)
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Steroid regulation : An overlooked aspect of tolerance and chronic rejection in kidney transplantation
- 2018
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Ingår i: Molecular and Cellular Endocrinology. - : ELSEVIER IRELAND LTD. - 0303-7207 .- 1872-8057. ; 473, s. 205-216
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Tidskriftsartikel (refereegranskat)abstract
- Steroid conversion (HSD11B1, HSD11B2, H6PD) and receptor genes (NR3C1, NR3C2) were examined in kidney-transplant recipients with "operational tolerance" and chronic rejection (CR), independently and within the context of 88 tolerance-associated genes. Associations with cellular types were explored. Peripheral whole-blood gene-expression levels (RT-qPCR-based) and cell counts were adjusted for immunosuppressant drug intake. Tolerant (n = 17), stable (n = 190) and CR patients (n = 37) were compared. Healthy controls (n= 14) were used as reference. The anti-inflammatory glucocorticoid receptor (NR3C1) and the cortisol-activating HSD11B1 and H6PD genes were up-regulated in CR and were lowest in tolerant patients. The pro-inflammatory mineralocorticoid gene (NR3C2) was downregulated in stable and CR patients. NR3C1 was associated with neutrophils and NR3C2 with T-cells. Steroid conversion and receptor genes, alone, enabled classification of tolerant patients and were major contributors to gene-expression signatures of both, tolerance and CR, alongside known tolerance-associated genes, revealing a key role of steroid regulation and response in kidney transplantation.
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| 8. |
- Christakoudi, Sofia, et al.
(författare)
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Weight change in middle adulthood and risk of cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort
- 2021
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 148:7, s. 1637-1651
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is a risk factor for several major cancers. Associations of weight change in middle adulthood with cancer risk, however, are less clear. We examined the association of change in weight and body mass index (BMI) category during middle adulthood with 42 cancers, using multivariable Cox proportional hazards models in the European Prospective Investigation into Cancer and Nutrition cohort. Of 241 323 participants (31% men), 20% lost and 32% gained weight (>0.4 to 5.0 kg/year) during 6.9 years (average). During 8.0 years of follow-up after the second weight assessment, 20 960 incident cancers were ascertained. Independent of baseline BMI, weight gain (per one kg/year increment) was positively associated with cancer of the corpus uteri (hazard ratio [HR] = 1.14; 95% confidence interval: 1.05-1.23). Compared to stable weight (±0.4 kg/year), weight gain (>0.4 to 5.0 kg/year) was positively associated with cancers of the gallbladder and bile ducts (HR = 1.41; 1.01-1.96), postmenopausal breast (HR = 1.08; 1.00-1.16) and thyroid (HR = 1.40; 1.04-1.90). Compared to maintaining normal weight, maintaining overweight or obese BMI (World Health Organisation categories) was positively associated with most obesity-related cancers. Compared to maintaining the baseline BMI category, weight gain to a higher BMI category was positively associated with cancers of the postmenopausal breast (HR = 1.19; 1.06-1.33), ovary (HR = 1.40; 1.04-1.91), corpus uteri (HR = 1.42; 1.06-1.91), kidney (HR = 1.80; 1.20-2.68) and pancreas in men (HR = 1.81; 1.11-2.95). Losing weight to a lower BMI category, however, was inversely associated with cancers of the corpus uteri (HR = 0.40; 0.23-0.69) and colon (HR = 0.69; 0.52-0.92). Our findings support avoiding weight gain and encouraging weight loss in middle adulthood.
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| 9. |
- Ellingjord-Dale, Merete, et al.
(författare)
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Long-term weight change and risk of breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study
- 2022
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Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 1464-3685 .- 0300-5771. ; 50:6, s. 1914-1926
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The role of obesity and weight change in breast-cancer development is complex and incompletely understood. We investigated long-term weight change and breast-cancer risk by body mass index (BMI) at age 20 years, menopausal status, hormone replacement therapy (HRT) and hormone-receptor status.METHODS: Using data on weight collected at three different time points from women who participated in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we investigated the association between weight change from age 20 years until middle adulthood and risk of breast cancer.RESULTS: In total, 150 257 women with a median age of 51 years at cohort entry were followed for an average of 14 years (standard deviation = 3.9) during which 6532 breast-cancer cases occurred. Compared with women with stable weight (±2.5 kg), long-term weight gain >10 kg was positively associated with postmenopausal breast-cancer risk in women who were lean at age 20 [hazard ratio (HR) = 1.42; 95% confidence interval 1.22-1.65] in ever HRT users (HR = 1.23; 1.04-1.44), in never HRT users (HR = 1.40; 1.16-1.68) and in oestrogen-and-progesterone-receptor-positive (ER+PR+) breast cancer (HR = 1.46; 1.15-1.85).CONCLUSION: Long-term weight gain was positively associated with postmenopausal breast cancer in women who were lean at age 20, both in HRT ever users and non-users, and hormone-receptor-positive breast cancer.
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| 10. |
- Harbs, Justin, et al.
(författare)
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Circulating Sex Hormone Levels and Colon Cancer Risk in Men : A Nested Case–Control Study and Meta-Analysis
- 2022
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 31:4, s. 793-803
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Tidskriftsartikel (refereegranskat)abstract
- Background: Endogenous sex hormones may contribute to higher colorectal cancer incidence rates in men compared with women, but despite an increased number of studies, clear evidence is lacking.Methods: We conducted a comprehensive nested case–control study of circulating concentrations of sex hormones, sex hormone precursors, and sex hormone binding globulin (SHBG) in relation to subsequent colon cancer risk in European men. Concentrations were measured using liquid LC/MS-MS in prospectively collected plasma samples from 690 cases and 690 matched controls from the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Northern Sweden Health and Disease Study (NSHDS) cohorts. Multivariable conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). In addition, we conducted a meta-analysis of previous studies on men.Results: Circulating levels of testosterone (OR, 0.68; 95% CI, 0.51–0.89) and SHBG (OR, 0.77; 95% CI, 0.62–0.96) were inversely associated with colon cancer risk. For free testosterone, there was a nonsignificant inverse association (OR, 0.83; 95% CI, 0.58–1.18). In a dose–response meta-analysis of endogenous sex hormone levels, inverse associations with colorectal/colon cancer risk were found for testosterone [relative risks (RR) per 100 ng/dL ¼ 0.98; 95% CI, 0.96–1.00; I2 ¼ 22%] and free testosterone (RR per 1 ng/dL ¼ 0.98; 95% CI, 0.95–1.00; I2 ¼ 0%).Conclusions: Our results provide suggestive evidence for the association between testosterone, SHBG, and male colon cancer development.Impact: Additional support for the involvement of sex hormones in male colon cancer.
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