| 1. |
- Vialas, Vital, et al.
(författare)
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A multicentric study to evaluate the use of relative retention times in targeted proteomics
- 2017
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Ingår i: Journal of Proteomics. - : Elsevier BV. - 1874-3919. ; 152, s. 138-149
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Tidskriftsartikel (refereegranskat)abstract
- Despite the maturity reached by targeted proteomic strategies, reliable and standardized protocols are urgently needed to enhance reproducibility among different laboratories and analytical platforms, facilitating a more widespread use in biomedical research. To achieve this goal, the use of dimensionless relative retention times (iRT), defined on the basis of peptide standard retention times (RT), has lately emerged as a powerful tool. The robustness, reproducibility and utility of this strategy were examined for the first time in a multicentric setting, involving 28 laboratories that included 24 of the Spanish network of proteomics laboratories (ProteoRed-ISCIII). According to the results obtained in this study, dimensionless retention time values (iRTs) demonstrated to be a useful tool for transferring and sharing peptide retention times across different chromatographic set-ups both intra- and inter-laboratories. iRT values also showed very low variability over long time periods. Furthermore, parallel quantitative analyses showed a high reproducibility despite the variety of experimental strategies used, either MRM (multiple reaction monitoring) or pseudoMRM, and the diversity of analytical platforms employed. Biological significance From the very beginning of proteomics as an analytical science there has been a growing interest in developing standardized methods and experimental procedures in order to ensure the highest quality and reproducibility of the results. In this regard, the recent (2012) introduction of the dimensionless retention time concept has been a significant advance. In our multicentric (28 laboratories) study we explore the usefulness of this concept in the context of a targeted proteomics experiment, demonstrating that dimensionless retention time values is a useful tool for transferring and sharing peptide retention times across different chromatographic set-ups.
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| 2. |
- Idahl, Annika, 1965-, et al.
(författare)
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Serologic markers of Chlamydia trachomatis and other sexually transmitted infections and subsequent ovarian cancer risk : Results from the EPIC cohort
- 2020
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 147:8, s. 2042-2052
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Tidskriftsartikel (refereegranskat)abstract
- A substantial proportion of epithelial ovarian cancer (EOC) arises in the fallopian tube and other epithelia of the upper genital tract; these epithelia may incur damage and neoplastic transformation after sexually transmitted infections (STI) and pelvic inflammatory disease. We investigated the hypothesis that past STI infection, particularly Chlamydia trachomatis, is associated with higher EOC risk in a nested case‐control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort including 791 cases and 1669 matched controls. Serum antibodies against C. trachomatis, Mycoplasma genitalium, herpes simplex virus type 2 (HSV‐2) and human papillomavirus (HPV) 16, 18 and 45 were assessed using multiplex fluorescent bead‐based serology. Conditional logistic regression was used to estimate relative risks (RR) and 95% confidence intervals (CI) comparing women with positive vs. negative serology. A total of 40% of the study population was seropositive to at least one STI. Positive serology to C. trachomatis Pgp3 antibodies was not associated with EOC risk overall, but with higher risk of the mucinous histotype (RR = 2.30 [95% CI = 1.22‐4.32]). Positive serology for chlamydia heat shock protein 60 (cHSP60‐1) was associated with higher risk of EOC overall (1.36 [1.13‐1.64]) and with the serous subtype (1.44 [1.12‐1.85]). None of the other evaluated STIs were associated with EOC risk overall; however, HSV‐2 was associated with higher risk of endometrioid EOC (2.35 [1.24‐4.43]). The findings of our study suggest a potential role of C. trachomatis in the carcinogenesis of serous and mucinous EOC, while HSV‐2 might promote the development of endometrioid disease.
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| 3. |
- Martinez, Emilio A., et al.
(författare)
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Achievements and future perspectives of embryo transfer technology in pigs
- 2019
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Ingår i: Reproduction in domestic animals. - : WILEY. - 0936-6768 .- 1439-0531. ; 54
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Tidskriftsartikel (refereegranskat)abstract
- Commercial embryo transfer (ET) has unprecedented productive and economic implications for the pig sector. However, pig ET has been considered utopian for decades mainly because of the requirements of surgical techniques for embryo collection and embryo deposition into recipients, alongside challenges to preserve embryos. This situation has drastically changed in the last decade since the current technology allows non-surgical ET and short- and long-term embryo preservation. Here, we provide a brief review of the improvements in porcine ET achieved by our laboratory in the past 20 years. This review includes several aspects of non-surgical ET technology and different issues affecting ET programmes and embryo preservation systems. The future perspectives of ET technology are also considered. We will refer only to embryos produced in vivo since they are the only type of embryos with possible short-term use in pig production.
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| 4. |
- Rodríguez Eguizabal, Eva, et al.
(författare)
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Capacidad de respuesta del sistema de salud en atención primaria valorada por pacientes con enfermedades crónicas : [Evaluation of health center's primary care responsiveness by patients with chronic illnesses]
- 2022
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Ingår i: Gaceta Sanitaria. - : Elsevier. - 0213-9111 .- 1578-1283. ; 36:3, s. 232-239
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Tidskriftsartikel (refereegranskat)abstract
- Objetivo: Evaluar la capacidad de respuesta del sistema de salud percibida por pacientes crónicos de atención primaria, así como los factores asociados a esa percepción.Método: Estudio transversal basado en entrevistas a pacientes mayores de 18 años diagnosticados de al menos una enfermedad crónica que visitaron los centros de atención primaria durante junio y julio de 2015 en una zona básica de Salud de La Rioja. El resultado fue el índice de respuesta y los factores potencialmente relacionados incluyeron características sociodemográficas y de salud. Entrevistadores capacitados realizaron el cuestionario breve en español de la encuesta multipaís de la Organización Mundial de la Salud con 403 participantes. Se realizaron estadística descriptiva y regresión logística bivariable y multivariable.Resultados: El 87,10% de los participantes consideró buena la respuesta general. Los dominios que obtuvieron las puntuaciones más altas fueron confidencialidad (99,3%), dignidad (98,3%) y comunicación (97,3%). Los peor evaluados fueron atención rápida (38,6%) y calidad de los servicios básicos (31,8%). La clase social baja fue el factor más importante asociado a la capacidad de respuesta, concretamente con la autonomía y la atención rápida. Sexo, educación y ocupación estuvieron relacionados con comunicación, y los pacientes con peor salud percibida valoraron peor la respuesta general. Los dominios considerados más importantes fueron dignidad (33,5%) y atención rápida (30,5%).Conclusiones: Los dominios mejor evaluados fueron los relacionados con el respeto a las personas. La atención rápida tiene una baja valoración, pero una gran importancia, y por lo tanto requiere una acción prioritaria.
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| 5. |
- Yammine, Sahar, et al.
(författare)
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Dietary and Circulating Fatty Acids and Ovarian Cancer Risk in the European Prospective Investigation into Cancer and Nutrition
- 2020
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - Philadelphia : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 29:9, s. 1739-1749
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Tidskriftsartikel (refereegranskat)abstract
- Background: Fatty acids impact obesity, estrogens, and inflammation, which are risk factors for ovarian cancer. Few epidemiologic studies have investigated the association of fatty acids with ovarian cancer.Methods: Within the European Prospective Investigation into Cancer and Nutrition (EPIC), 1,486 incident ovarian cancer cases were identified. Cox proportional hazard models with adjustment for ovarian cancer risk factors were used to estimate HRs of ovarian cancer across quintiles of intake of fatty acids. False discovery rate was computed to control for multiple testing. Multivariable conditional logistic regression models were used to estimate ORs of ovarian cancer across tertiles of plasma fatty acids among 633 cases and two matched controls in a nested case-control analysis.Results: Apositive association was found between ovarian cancer and intake of industrial trans elaidic acid [HR comparing fifth with first quintile(Q5-Q1) = 1.29; 95% confidence interval (CI) = 1.03-1.62; P-trend = 0.02, q-value = 0.06]. Dietary intakes of n-6 linoleic acid (HRQ5-Q1 = 1.10; 95% CI = 1.01-1.21; P-trend = 0.03) and n-3 alpha-linolenic acid (HRQ5-Q1 = 1.18; 95% CI = 1.05-1.34; P-trend = 0.007) from deep-frying fats were also positively associated with ovarian cancer. Suggestive associations were reported for circulating elaidic (OR comparing third with first tertile(T3-T1) = 1.39; 95% CI = 0.99-1.94; P-trend = 0.06) anda-linolenic acids (ORT3-T1 = 1.30; 95% CI = 0.98-1.72; P-trend = 0.06).Conclusions: Our results suggest that higher intakes and circulating levels of industrial trans elaidic acid, and higher intakes of linoleic acid and alpha-linolenic acid from deep-frying fat, may be associated with greater risk of ovarian cancer.Impact: If causal, eliminating industrial trans-fatty acids could offer a straightforward public health action for reducing ovarian cancer risk.
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| 6. |
- Cervenka, Iris, et al.
(författare)
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Exogenous hormone use and cutaneous melanoma risk in women : The European Prospective Investigation into Cancer and Nutrition
- 2020
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 146:12, s. 3267-3280
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Tidskriftsartikel (refereegranskat)abstract
- Evidence suggests an influence of sex hormones on cutaneous melanoma risk, but epidemiologic findings are conflicting. We examined the associations between use of oral contraceptives (OCs) and menopausal hormone therapy (MHT) and melanoma risk in women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a prospective cohort study initiated in 1992 in 10 European countries. Information on exogenous hormone use at baseline was derived from country‐specific self‐administered questionnaires. We used Cox proportional hazards regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Over 1992–2015, 1,696 melanoma cases were identified among 334,483 women, whereof 770 cases among 134,758 postmenopausal women. There was a positive, borderline‐significant association between OC use and melanoma risk (HR = 1.12, 95% CI = 1.00–1.26), with no detected heterogeneity across countries (phomogeneity = 0.42). This risk increased linearly with duration of use (ptrend = 0.01). Among postmenopausal women, ever use of MHT was associated with a nonsignificant increase in melanoma risk overall (HR = 1.14, 95% CI = 0.97–1.43), which was heterogeneous across countries (phomogeneity = 0.05). Our findings do not support a strong and direct association between exogenous hormone use and melanoma risk. In order to better understand these relations, further research should be performed using prospectively collected data including detailed information on types of hormone, and on sun exposure, which may act as an important confounder or effect modifier on these relations.
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| 7. |
- Gonzalez-Plaza, Alejandro, et al.
(författare)
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Equilibration time with cryoprotectants, but not melatonin supplementation during in vitro maturation, affects viability and metaphase plate morphology of vitrified porcine mature oocytes
- 2022
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Ingår i: Reproduction in domestic animals. - : Wiley. - 0936-6768 .- 1439-0531. ; 57:S5, s. 58-63
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Tidskriftsartikel (refereegranskat)abstract
- The aims of this study were to investigate the effects of different equilibration times with cryoprotectants on viability and metaphase plate morphology of vitrified-warmed porcine mature oocytes (Experiment 1) and to evaluate the effects of supplementation with 10(-9) M melatonin during in vitro maturation on these parameters (Experiment 2). In Experiment 1, 2,392 mature oocytes were vitrified using different equilibration times of oocytes with cryoprotectants (3, 10, 15, 20, 30, 40, 60 and 80 min). Fresh oocytes matured in vitro for 44 hr (n = 509) were used as controls. In Experiment 2, a total of 573 COCs were used. COCs were matured with 10(-9) M melatonin supplementation or without melatonin (control). Some oocytes from each group were vitrified with a 60-min equilibration time with cryoprotectants according to the results of Experiment 1. The remaining oocytes from each maturation group were used as fresh control groups. In both experiments, oocytes were stained with 2 ,7 -dichlorodihydrofuorescein diacetate and Hoechst 33342 to assess viability and metaphase plate morphology, respectively. Vitrification and warming affected (p < .01) oocyte viability compared with controls, which were all viable after 44 hr of IVM. In Experiment 1, the longer the equilibration time with cryoprotectants, the higher the viability. Oocytes equilibrated for 60 and 80 min had the highest (p < .05) viability and similar metaphase plate characteristics to the fresh control oocytes. In Experiment 2, supplementation with melatonin during in vitro maturation had no effect on oocyte viability or metaphase plate morphology of vitrified-warmed oocytes. In conclusion, under our experimental conditions, vitrified porcine mature oocytes equilibrated with cryoprotectants for 60 or 80 min exhibited the highest viability and similar metaphase plate characteristics to fresh controls. Furthermore, supplementation with 10(-9) M melatonin during in vitro maturation had no effect on these parameters.
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| 8. |
- Gonzalez-Ramiro, Henar, et al.
(författare)
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Combined synchronization and superovulation treatments negatively impact embryo viability possibly by the downregulation of WNT/beta-catenin and Notch signaling genes in the porcine endometrium
- 2022
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Ingår i: Journal of Animal Science. - : Oxford University Press. - 0021-8812 .- 1525-3163. ; 100:11
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Tidskriftsartikel (refereegranskat)abstract
- The combination of estrus synchronization and superovulation treatments introduces molecular modifications whose effects are yet to be disclosed. Here, reproductive parameters and gene expression changes in ovaries and endometrium were explored on day 6 after artificial insemination (AI), when synthetic progestin altrenogest (ALT) was combined with gonadotropins. Sows were administered ALT for 7 d beginning on the day of weaning and superovulated with equine chorionic gonadotropin (eCG) 24 h later and human chorionic gonadotropins (hCG) at the onset of estrus (SS-7 group; n = 6). The controls were either superovulated sows with eCG 24 h postweaning and hCG at the onset of estrus (SC group; n = 6) or sows with postweaning spontaneous estrus (NC group; n = 6). Ovary examination and embryo and tissue collection were performed in all sows via laparotomy on day 6 post-AI. RNA-Seq was conducted to analyze differentially expressed genes (DEGs) between groups. Statistical analysis of the reproductive parameters was conducted with ANOVA and Tukey post hoc tests. DEGs were analyzed with an ANOVA (fold changes >= 2 or <= 2, P value <0.05). Hormonal treatments almost doubled (P < 0.03) the number of corpora lutea (39.8 +/- 10.2 and 38.3 +/- 11.1 in SS-7 and SC sows, respectively) compared with that in the NC group (23.1 +/- 3.8). In contrast, embryo viability significantly decreased (P < 0.003) in response to SS-7 treatment (75.1% +/- 15.2%) compared to SC and NC groups (93.8 +/- 7.6% and 91.8 +/- 6.9%, respectively). RNA-Seq analyses revealed 675 and 1,583 DEGs in the SS-7 group compared to both SC and NC groups in endometrial and ovarian samples, respectively. Interestingly, many genes with key roles in the Wnt/beta-catenin and Notch signaling pathways were differentially expressed in SS-7 sows relative to SC and NC groups (e.g., Ctnnb1, Myc, Gli3, Scyl2, Ccny, Daam1, Ppm1n, Rbpj, and Usp8). A key finding in this study was the downregulation of beta-catenin (Ctnnb1) gene expression in the SS-7 endometrium, suggesting that this treatment influences embryo-uterine dialogue by triggering a cascade of events leading to embryo maldevelopment. These data explain the proliferative defects in SS-7 embryos and suggest a novel mechanism of a porcine embryo-maternal crosstalk. Lay Summary Methods for porcine superovulation (increasing the number of ovulated oocytes per cycle) and estrus synchronization (grouping estrus sows on the same day) are available for assisted reproductive technologies, using hormonal treatments. The main goal of the present study was to understand how hormones used for these purposes influence gene expression patterns in the female reproductive tract (ovaries and endometrium). We observed that hormonal treatments (synchronization combined with superovulation) have the potential to alter ovarian and endometrial gene expression patterns, triggering improper follicle development and oocyte growth, and leading to abnormal embryonic development before implantation. Genes involved in two key metabolic pathways for embryo development (Wnt/beta-catenin and Notch signaling pathways) were dysregulated in reproductive tissues.
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| 9. |
- Maside, Carolina, et al.
(författare)
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Supplementation with exogenous coenzyme Q10 to media for in vitro maturation and embryo culture fails to promote the developmental competence of porcine embryos
- 2019
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Ingår i: Reproduction in domestic animals. - : WILEY. - 0936-6768 .- 1439-0531. ; 54, s. 72-77
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Tidskriftsartikel (refereegranskat)abstract
- The coenzyme Q10 (CoQ10) is a potent antioxidant with critical protection role against cell oxidative stress, caused by the mitochondrial dysfunction. This study evaluated the effects of CoQ10 supplementation to in vitro maturation (IVM) or embryo culture media on the maturation, fertilization and subsequent embryonic development of pig oocytes and embryos. Maturation (Experiment 1) or embryo culture (Experiment 2) media were supplemented with 0 (control), 10, 25, 50 and 100 mu M CoQ10. The addition of 10-50 mu M CoQ10 to the IVM medium did not affect the percentage of MII oocytes nor the fertilization or the parameters of subsequent embryonic development. Exogenous CoQ10 in the culture medium neither did affect the development to the 2-4-cell stage nor rates of blastocyst formation. Moreover, the highest concentration of CoQ10 (100 mu M) in the maturation medium negatively affected blastocyst rates. In conclusion, exogenous CoQ10 supplementation of maturation or embryo culture media failed to improve the outcomes of our in vitro embryo production system and its use as an exogenous antioxidant should not be encouraged.
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| 10. |
- Murphy, Neil, et al.
(författare)
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Heterogeneity of Colorectal Cancer Risk Factors by Anatomical Subsite in 10 European Countries : A Multinational Cohort Study
- 2019
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Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 17:7, s. 1323-1331
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Colorectal cancer located at different anatomical subsites may have distinct etiologies and risk factors. Previous studies that have examined this hypothesis have yielded inconsistent results, possibly because most studies have been of insufficient size to identify heterogeneous associations with precision.Methods: In the European Prospective Investigation into Cancer and Nutrition study, we used multivariable joint Cox proportional hazards models, which accounted for tumorsat different anatomical sites (proximal colon, distal colon, and rectum) as competing risks, to examine the relationships between 14 established/suspected lifestyle, anthropometric, and reproductive/menstrual risk factors with colorectal cancer risk. Heterogeneity across sites was tested using Wald tests.Results: After a median of 14.9 years of follow-up of 521,330 men and women, 6291 colorectal cancer cases occurred. Physical activity was related inversely to proximal colon and distal colon cancer, but not to rectal cancer (P heterogeneity = .03). Height was associated positively with proximal and distal colon cancer only, but not rectal cancer (P heterogeneity = .0001). For men, but not women, heterogeneous relationships were observed for body mass index (P heterogeneity = .008) and waist circumference (P heterogeneity = .03), with weaker positive associations found for rectal cancer, compared with proximal and distal colon cancer. Current smoking was associated with a greater risk of rectal and proximal colon cancer, but not distal colon cancer (P heterogeneity = .05). No heterogeneity by anatomical site was found for alcohol consumption, diabetes, nonsteroidal anti-inflammatory drug use, and reproductive/menstrual factors.Conclusions: The relationships between physical activity, anthropometry, and smoking with colorectal cancer risk differed by subsite, supporting the hypothesis that tumors in different anatomical regions may have distinct etiologies.
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| 11. |
- Parrilla, Inmaculada, et al.
(författare)
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Boar seminal plasma: current insights on its potential role for assisted reproductive technologies in swine
- 2020
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Ingår i: Animal Reproduction. - : BRAZILIAN COLL ANIMAL REPRODUCTION. - 1806-9614 .- 1984-3143. ; 17:3
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Tidskriftsartikel (refereegranskat)abstract
- Seminal plasma (SP) supports not only sperm function but also the ability of spermatozoa to withstand biotechnological procedures as artificial insemination, freezing or sex sorting. Moreover, evidence has been provided that SP contains identifiable molecules which can act as fertility biomarkers, and even improve the output of assisted reproductive technologies by acting as modulators of endometrial and embryonic changes of gene expression, thus affecting embryo development and fertility beyond the sperm horizon. In this overview, we discuss current knowledge of the composition of SP, mainly proteins and cytokines, and their influence on semen basic procedures, such as liquid storage or cryopreservation. The role of SP as modulator of endometrial and embryonic molecular changes that lead to successful pregnancy will also be discussed.
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| 12. |
- Parrilla, Inmaculada, et al.
(författare)
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Immunological uterine response to pig embryos before and during implantation
- 2022
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Ingår i: Reproduction in domestic animals. - : Wiley. - 0936-6768 .- 1439-0531. ; 58:S5, s. 4-13
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Forskningsöversikt (refereegranskat)abstract
- The establishment of a successful pregnancy can only occur through a concerted functioning of the entire female reproductive system, allowing for fertilization, subsequent embryo development and implantation of the conceptus. In this context, the uterine immunological responses responsible for rejection or tolerance of the conceptus are of critical importance. The aim of the present review is to summarize our current knowledge about those cellular and molecular immunological events occurring at the uterine level during pre-implantation and implantation stages of pregnancy in the pig. Advancing our understanding of the immune mechanisms involved in the success or failure of pregnancy will provide cues to develop novel strategies augmenting endometrial receptivity, finally increasing the efficiency of assisted reproductive technologies in pigs.
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| 13. |
- Parrilla, Inmaculada, et al.
(författare)
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Neither frozen-thawed seminal plasma nor commercial transforming growth factor-beta 1 infused intra-utero before insemination improved fertility and prolificacy in sows
- 2022
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Ingår i: Reproduction in domestic animals. - : Wiley. - 0936-6768 .- 1439-0531. ; 57:S5, s. 86-89
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Tidskriftsartikel (refereegranskat)abstract
- Seminal plasma (SP) affects reproduction, inducing cell and molecular changes in the female genital tract. A main active component in SP is the modulatory transforming growth factor-beta (TGF-beta), particularly its TGF-beta 1 isoform, which affects the synthesis of other cytokines as granulocyte-macrophage colony-stimulating factor, relevant for embryo development and pregnancy. This study evaluated the effect of pooled frozen-thawed SP and commercial TGF-beta 1 infused during oestrus in sows post-cervically inseminated with liquid extended semen, containing similar to 4 ml of residual SP, on their fertility and prolificacy. For this, 250 sows in their post-weaning oestrus were used. Sows were randomly assigned to one of the following groups to be post-cervically treated 30 min before insemination: (i) SP group: infused with 40 ml of SP (N = 57); ii) Group TFG(beta 1): infused with 40 ml of BTS extender containing 3 ng/ml of porcine TGF-beta 1 (N = 64); iii) BTS group: infused with 40 ml of BTS extender (N = 60); and iv) Control Group: sows catheterized but not infused prior to Al (N = 69). Farrowing rates (range: 86.7% to 91.3%) and numbers of live-born piglets (range: range: 12.8 +/- 2.9 to 13.4 +/- 3.1) were not affected by any treatment compared with Controls, indicating that neither pre-infusions of SP nor TGF-beta 1 30 min before Al influenced subsequent fertility and prolificacy.
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| 14. |
- Perez-Cornago, Aurora, et al.
(författare)
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Circulating isoflavone and lignan concentrations and prostate cancer risk: a meta-analysis of individual participant data from seven prospective studies including 2,828 cases and 5,593 controls
- 2018
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 143:11, s. 2677-2686
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Tidskriftsartikel (refereegranskat)abstract
- Phytoestrogens may influence prostate cancer development. This study aimed to examine the association between prediagnostic circulating concentrations of isoflavones (genistein, daidzein, equol) and lignans (enterolactone and enterodiol) and the risk of prostate cancer. Individual participant data were available from seven prospective studies (two studies from Japan with 241 cases and 503 controls and five studies from Europe with 2,828 cases and 5,593 controls). Because of the large difference in circulating isoflavone concentrations between Japan and Europe, analyses of the associations of isoflavone concentrations and prostate cancer risk were evaluated separately. Prostate cancer risk by study-specific fourths of circulating concentrations of each phytoestrogen was estimated using multivariable-adjusted conditional logistic regression. In men from Japan, those with high compared to low circulating equol concentrations had a lower risk of prostate cancer (multivariable-adjusted OR for upper quartile [Q4] vs. Q1 = 0.61, 95% confidence interval [CI] = 0.39–0.97), although there was no significant trend (OR per 75 percentile increase = 0.69, 95 CI = 0.46–1.05, ptrend = 0.085); Genistein and daidzein concentrations were not significantly associated with risk (ORs for Q4 vs. Q1 = 0.70, 0.45–1.10 and 0.71, 0.45–1.12, respectively). In men from Europe, circulating concentrations of genistein, daidzein and equol were not associated with risk. Circulating lignan concentrations were not associated with the risk of prostate cancer, overall or by disease aggressiveness or time to diagnosis. There was no strong evidence that prediagnostic circulating concentrations of isoflavones or lignans are associated with prostate cancer risk, although further research is warranted in populations where isoflavone intakes are high.
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| 15. |
- Seyed Khoei, Nazlisadat, et al.
(författare)
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Circulating bilirubin levels and risk of colorectal cancer : serological and Mendelian randomization analyses
- 2020
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Ingår i: BMC Medicine. - : Springer Nature. - 1741-7015. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Bilirubin, a byproduct of hemoglobin breakdown and purported anti-oxidant, is thought to be cancer preventive. We conducted complementary serological and Mendelian randomization (MR) analyses to investigate whether alterations in circulating levels of bilirubin are associated with risk of colorectal cancer (CRC). We decided a priori to perform analyses separately in men and women based on suggestive evidence that associations may differ by sex.METHODS: In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC), pre-diagnostic unconjugated bilirubin (UCB, the main component of total bilirubin) concentrations were measured by high-performance liquid chromatography in plasma samples of 1386 CRC cases and their individually matched controls. Additionally, 115 single-nucleotide polymorphisms (SNPs) robustly associated (P < 5 × 10-8) with circulating total bilirubin were instrumented in a 2-sample MR to test for a potential causal effect of bilirubin on CRC risk in 52,775 CRC cases and 45,940 matched controls in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colon Cancer Family Registry (CCFR), and the Colorectal Transdisciplinary (CORECT) study.RESULTS: The associations between circulating UCB levels and CRC risk differed by sex (Pheterogeneity = 0.008). Among men, higher levels of UCB were positively associated with CRC risk (odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.04-1.36; per 1-SD increment of log-UCB). In women, an inverse association was observed (OR = 0.86 (0.76-0.97)). In the MR analysis of the main UGT1A1 SNP (rs6431625), genetically predicted higher levels of total bilirubin were associated with a 7% increase in CRC risk in men (OR = 1.07 (1.02-1.12); P = 0.006; per 1-SD increment of total bilirubin), while there was no association in women (OR = 1.01 (0.96-1.06); P = 0.73). Raised bilirubin levels, predicted by instrumental variables excluding rs6431625, were suggestive of an inverse association with CRC in men, but not in women. These differences by sex did not reach formal statistical significance (Pheterogeneity ≥ 0.2).CONCLUSIONS: Additional insight into the relationship between circulating bilirubin and CRC is needed in order to conclude on a potential causal role of bilirubin in CRC development.
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