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Lundin, Eva
Publications (10 of 133) Show all publications
Israelsson, P., Björk, E., Nagaev, I., Nagaeva, O., Lundin, E., Mincheva-Nilsson, L. & Ottander, U. (2023). NKG2D-mediated cytotoxicity improves after primary surgery for high-grade serous ovarian cancer. American Journal of Reproductive Immunology, 89(1), Article ID e13647.
Open this publication in new window or tab >>NKG2D-mediated cytotoxicity improves after primary surgery for high-grade serous ovarian cancer
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2023 (English)In: American Journal of Reproductive Immunology, ISSN 1046-7408, E-ISSN 1600-0897, Vol. 89, no 1, article id e13647Article in journal (Refereed) Published
Abstract [en]

Problem: Tumors compromise the patients’ immune system to promote their own survival. We have previously reported that HGSC exosomes play a central role, downregulating NKG2D cytotoxicity. Primary surgery's effect on tumor exosomes and NKG2D cytotoxicity in HGSC patients has not been studied before. The overall objective of this study was to explore the effect of surgery on the exosome-induced impairment of NKG2D cytotoxicity in HGSC.

Method of study: Paired pre- and post-operative blood samples were subjected to cell and exosome analyses regarding the NKG2D receptor and ligands, and NKG2D-mediated cytotoxicity. Lymphocytes were phenotyped by immunoflow cytometry. Exosomes, isolated by ultracentrifugation, and characterized by nanoparticle tracking analysis, transmission and immune electron microscopy and western blot were used in functional cytotoxic experiments. HGSC explant culture-derived exosomes, previously studied by us, were used for comparison.

Results: HGSC exosomes from patients’ sera downregulated NKG2D-mediated cytotoxicity in NK cells of healthy donors. In a subgroup of subjects, NKG2D expression on CTLs and NK cells was upregulated after surgery, correlating to a decrease in the concentration of exosomes in postoperative sera. An overall significantly improved NKG2D-mediated cytotoxic response of the HGSC patients’ own NK cells in postoperative compared to preoperative samples was noted.

Conclusions: Surgical removal of the primary tumor has a beneficial effect, relieving the exosome-mediated suppression of NKG2D cytotoxicity in HGSC patients, thus boostering their ability to combat cancer.

Place, publisher, year, edition, pages
John Wiley & Sons, 2023
Keywords
cytotoxicity, EOC/HGSC, epithelial ovarian cancer, exosomes, immune suppression, NKG2D, NKG2D ligands, surgery
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:umu:diva-201334 (URN)10.1111/aji.13647 (DOI)000888859600001 ()36335434 (PubMedID)2-s2.0-85142285991 (Scopus ID)
Funder
Swedish Research Council, 18-20–345240311Swedish Cancer Society, CAN 2018/350; no. 18 07 17
Available from: 2022-12-15 Created: 2022-12-15 Last updated: 2022-12-30Bibliographically approved
Jonsson, S., Jonsson, H., Lundin, E., Häggström, C. & Idahl, A. (2023). Pelvic inflammatory disease and risk of epithelial ovarian cancer: a national population-based case-control study in Sweden. American Journal of Obstetrics and Gynecology, 230(1), 75.e1-75.e15
Open this publication in new window or tab >>Pelvic inflammatory disease and risk of epithelial ovarian cancer: a national population-based case-control study in Sweden
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2023 (English)In: American Journal of Obstetrics and Gynecology, ISSN 0002-9378, E-ISSN 1097-6868, Vol. 230, no 1, p. 75.e1-75.e15Article in journal (Refereed) Published
Abstract [en]

Background: Epithelial ovarian cancer is an insidious disease, and women are often diagnosed when the disease is beyond curative treatment. Accordingly, identifying modifiable risk factors is of paramount importance. Inflammation predisposes an individual to cancer in various organs, but whether pelvic inflammatory disease is associated with an increased risk of epithelial ovarian cancer has not been fully determined.

Objective: This study aimed to investigate a possible association between clinically verified pelvic inflammatory disease and the risk of epithelial ovarian cancer.

Study Design: In this national population-based case-control study, all women in Sweden diagnosed with epithelial ovarian cancer between 1999 and 2020 and 10 controls for each were identified, matched for age and residential district. Using several Swedish nationwide registers, data on previous pelvic inflammatory disease and potential confounding factors (age, parity, educational level, and previous gynecologic surgery) were retrieved. Adjusted odds ratios and 95% confidence intervals were estimated using conditional logistic regression. Histotype-specific analyses were performed for the subgroup of women diagnosed with epithelial ovarian cancer between 2015 and 2020. Moreover, hormonal contraceptives and menopausal hormone therapy were adjusted in addition to the aforementioned confounders.

Results: This study included 15,072 women with epithelial ovarian cancer and 141,322 controls. Most women (9102 [60.4%]) had serous carcinoma. In a subgroup of cases diagnosed between 2015 and 2020, high-grade serous carcinoma (2319 [60.0%]) was identified. A total of 168 cases (1.1%) and 1270 controls (0.9%) were diagnosed with pelvic inflammatory disease. Previous pelvic inflammatory disease was associated with an increased risk of epithelial ovarian cancer (adjusted odds ratio, 1.39; 95% confidence interval, 1.17–1.66) and serous carcinoma (adjusted odds ratio, 1.46; 95% confidence interval, 1.18–1.80) for the entire study population. For the subgroup of women diagnosed in 2015–2020, pelvic inflammatory disease was associated with high-grade serous carcinoma (adjusted odds ratio, 1.43; 95% confidence interval, 1.01–2.04). The odds ratios of the other histotypes were as follows: endometrioid (adjusted odds ratio, 0.13; 95% confidence interval, 0.02–1.06), mucinous (adjusted odds ratio, 1.55; 95% confidence interval, 0.56–4.29), and clear cell carcinoma (adjusted odds ratio, 2.30; 95% confidence interval, 0.90–5.86). A dose-response relationship was observed between the number of pelvic inflammatory disease episodes and the risk of epithelial ovarian cancer (Ptrend<.001).

Conclusion: A history of pelvic inflammatory disease is associated with an increased risk of epithelial ovarian cancer and a dose-response relationship is evident. Histotype-specific analyses show an association with increased risk of serous epithelial ovarian cancer and high-grade serous carcinoma and potentially also with clear cell carcinoma, but there is no significant association with other histotypes. Infection and inflammation of the upper reproductive tract might have serious long-term consequences, including epithelial ovarian cancer.

Place, publisher, year, edition, pages
Elsevier, 2023
Keywords
epithelial ovarian cancer, high-grade serous carcinoma, ovarian cancer, pelvic inflammatory disease, population-based case-control study
National Category
Obstetrics, Gynecology and Reproductive Medicine Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-216205 (URN)10.1016/j.ajog.2023.09.094 (DOI)37778677 (PubMedID)2-s2.0-85175294490 (Scopus ID)
Available from: 2023-11-06 Created: 2023-11-06 Last updated: 2024-01-05Bibliographically approved
Mukama, T., Fortner, R. T., Katzke, V., Hynes, L. C., Petrera, A., Hauck, S. M., . . . Kaaks, R. (2022). Prospective evaluation of 92 serum protein biomarkers for early detection of ovarian cancer. British Journal of Cancer, 126, 1301-1309
Open this publication in new window or tab >>Prospective evaluation of 92 serum protein biomarkers for early detection of ovarian cancer
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2022 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 126, p. 1301-1309Article in journal (Refereed) Published
Abstract [en]

Background: CA125 is the best available yet insufficiently sensitive biomarker for early detection of ovarian cancer. There is a need to identify novel biomarkers, which individually or in combination with CA125 can achieve adequate sensitivity and specificity for the detection of earlier-stage ovarian cancer.

Methods: In the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we measured serum levels of 92 preselected proteins for 91 women who had blood sampled ≤18 months prior to ovarian cancer diagnosis, and 182 matched controls. We evaluated the discriminatory performance of the proteins as potential early diagnostic biomarkers of ovarian cancer.

Results: Nine of the 92 markers; CA125, HE4, FOLR1, KLK11, WISP1, MDK, CXCL13, MSLN and ADAM8 showed an area under the ROC curve (AUC) of ≥0.70 for discriminating between women diagnosed with ovarian cancer and women who remained cancer-free. All, except ADAM8, had shown at least equal discrimination in previous case-control comparisons. The discrimination of the biomarkers, however, was low for the lag-time of >9–18 months and paired combinations of CA125 with any of the 8 markers did not improve discrimination compared to CA125 alone.

Conclusion: Using pre-diagnostic serum samples, this study identified markers with good discrimination for the lag-time of 0–9 months. However, the discrimination was low in blood samples collected more than 9 months prior to diagnosis, and none of the markers showed major improvement in discrimination when added to CA125.

Place, publisher, year, edition, pages
Springer Nature, 2022
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-191667 (URN)10.1038/s41416-021-01697-z (DOI)000742583500001 ()35031764 (PubMedID)2-s2.0-85122722777 (Scopus ID)
Available from: 2022-01-21 Created: 2022-01-21 Last updated: 2022-07-15Bibliographically approved
Patthey, A., Boman, K., Tavelin, B., Lindquist, D., Lundin, E. & Hultdin, M. (2021). Combination of aneuploidy and high S-phase fraction indicates increased risk of relapse in stage I endometrioid endometrial carcinoma. Acta Oncologica, 60(9), 1218-1224
Open this publication in new window or tab >>Combination of aneuploidy and high S-phase fraction indicates increased risk of relapse in stage I endometrioid endometrial carcinoma
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2021 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 60, no 9, p. 1218-1224Article in journal (Refereed) Published
Abstract [en]

INTRODUCTION: Endometrioid endometrial carcinoma is a cancer type with generally excellent prognosis when diagnosed at an early stage, but there is a subset of patients with relapsing disease in spite of early diagnosis and surgical treatment. There is a need to find prognostic markers to identify these patients with increased risk of relapse. Depth of myometrial invasion, histological grade, and presence of lymphovascular invasion are known risk factors. DNA content (ploidy) and proliferation measured as S-phase fraction (SPF) have been discussed as prognostic markers but need additional evaluation.

MATERIAL AND METHODS: We evaluated relapse-free survival (RFS) with respect to ploidy and SPF, which was analyzed by flow cytometry on fresh tumor tissue, in a cohort of 1001 women treated for stage I endometrioid endometrial carcinoma in northern Sweden during the period of 1993-2010, with a median follow up time of 12.0 years. Data were obtained from historical records.

RESULTS: In simple analysis, both aneuploidy and high SPF were associated to increased risk of relapse with hazard ratios (HR) 2.37 (95% CI 1.52-3.70) and 1.94 (95% CI 1.24-3.02), respectively. Our data also confirmed stage, tumor grade, and ploidy as independent prognostic markers in an age adjusted cox regression multivariable analysis but we did not find SPF to contribute to prognosis. However, the combination of aneuploidy and high SPF identified a group of patients with increased risk of relapse, HR 2.02 (95% CI 1.19-3.44).

CONCLUSION: In this study, which is the largest study of ploidy and SPF in stage I endometrioid endometrial carcinoma using fresh frozen tissue, aneuploidy was shown to be an independent prognostic marker. Furthermore, the combination of aneuploidy and high SPF could be used to identify patients with increased risk of relapse.

Place, publisher, year, edition, pages
Taylor & Francis Group, 2021
Keywords
Endometrioid Endometrial Carcinoma, Ploidy, Prognosis, S-phase fraction
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-185073 (URN)10.1080/0284186X.2021.1939146 (DOI)000665673800001 ()34156893 (PubMedID)2-s2.0-85108629114 (Scopus ID)
Funder
Region Västerbotten
Available from: 2021-06-23 Created: 2021-06-23 Last updated: 2023-03-24Bibliographically approved
Hathaway, C. A., Rice, M. S., Townsend, M. K., Hankinson, S. E., Arslan, A. A., Buring, J. E., . . . Tworoger, S. S. (2021). Prolactin and risk of epithelial ovarian cancer. Cancer Epidemiology, Biomarkers and Prevention, 30(9), 1652-1659
Open this publication in new window or tab >>Prolactin and risk of epithelial ovarian cancer
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2021 (English)In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 30, no 9, p. 1652-1659Article in journal (Refereed) Published
Abstract [en]

Background: Prolactin is synthesized in the ovaries and may play a role in ovarian cancer etiology. One prior prospective study observed a suggestive positive association between prolactin levels and risk of ovarian cancer.

Methods: Weconducted a pooled case-control study of 703 cases and 864 matched controls nested within five prospective cohorts. We used unconditional logistic regression to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI) for the association between prolactin and ovarian cancer risk. We examined heterogeneity by menopausal status at blood collection, body mass index (BMI), age, and histotype.

Results: Among women with known menopausal status, we observed a positive trend in the association between prolactin and ovarian cancer risk (Ptrend = 0.045; OR, quartile 4 vs. 1 = 1.34; 95% CI = 0.97–1.85), but no significant association was observed for premenopausal or postmenopausal women individually (corresponding OR = 1.38; 95% CI = 0.74–2.58; Ptrend = 0.32 and OR = 1.41; 95% CI = 0.93–2.13; Ptrend = 0.08, respectively; Pheterogeneity = 0.91). In stratified analyses, we observed a positive association between prolactin and risk for women with BMI ≥ 25 kg/m2, but not BMI < 25 kg/m2 (corresponding OR = 2.68; 95% CI = 1.56–4.59; Ptrend < 0.01 and OR = 0.90; 95% CI = 0.58–1.40; Ptrend = 0.98, respectively; Pheterogeneity < 0.01). Associations did not vary by age, postmenopausal hormone therapy use, histotype, or time between blood draw and diagnosis.

Conclusions: We found a trend between higher prolactin levels and increased ovarian cancer risk, especially among women with a BMI ≥ 25 kg/m2.

Impact: This work supports a previous study linking higher prolactin with ovarian carcinogenesis in a high adiposity setting. Future work is needed to understand the mechanism underlying this association.

Place, publisher, year, edition, pages
American Association for Cancer Research (AACR), 2021
National Category
Cancer and Oncology Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-187455 (URN)10.1158/1055-9965.EPI-21-0139 (DOI)000696386200009 ()34244157 (PubMedID)2-s2.0-85114143616 (Scopus ID)
Funder
Region VästerbottenNIH (National Institute of Health), CA047988, CA182913, HL043851, HL080467, HL099355, P01 CA87969, P30 CA016087, P30 ES000260, R01 CA49449, R01 CA67262, U01 CA176726, U01 CA186107, UM1 CA182934, VR 2017–00650KSwedish Research Council
Available from: 2021-09-13 Created: 2021-09-13 Last updated: 2022-10-31Bibliographically approved
Razumova, Z., Oda, H., Govorov, I., Lundin, E., Östensson, E., Lindquist, D. & Mints, M. (2021). The prognostic role of lrig proteins in endometrial cancer. Cancers, 13(6), 1-12, Article ID 1361.
Open this publication in new window or tab >>The prognostic role of lrig proteins in endometrial cancer
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2021 (English)In: Cancers, ISSN 2072-6694, Vol. 13, no 6, p. 1-12, article id 1361Article in journal (Refereed) Published
Abstract [en]

Endometrial cancer (EC) is the most common gynecologic malignancy in Sweden and it has various prognostic factors. The LRIG family is a group of three integral surface proteins with a similar domain organization. The study aimed to explore LRIG family as prognostic factor proteins in EC. The initial study cohort included 100 women with EC who were treated at the Department of Women’s and Children’s Health, Karolinska University Hospital Solna, between 2007 and 2012. We assessed the associations between LRIG protein expression and type, grade, and stage of EC, as well as progression‐free and overall survival. Immunohistochemistry results revealed that most women in the analytical sample had >50% LRIG1‐, LRIG2‐ and LRIG3‐positive cells. A statistically significant association was observed between having a high number of LRIG3‐positive cells and superior overall survival (incidence rate ratio = 0.977; 95% confidence interval: 0.958–0.996, p = 0.019). Moreover, positive LRIG3 staining of the cell membrane was associated with reducing in the risk of death (hazard ratio = 0.23; 95% confidence interval: 0.09–0.57). Our results show that LRIG3 expression might be a prognostic factor in EC. The role of LRIG1 and LRIG2 expression remains to be further investigated.

Place, publisher, year, edition, pages
MDPI, 2021
Keywords
Endometrial cancer, LRIG1, LRIG2, LRIG3, Prognosis
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-181783 (URN)10.3390/cancers13061361 (DOI)000634344300001 ()2-s2.0-85102558250 (Scopus ID)
Funder
Cancerforskningsfonden i Norrland
Available from: 2021-04-01 Created: 2021-04-01 Last updated: 2023-10-04Bibliographically approved
Jonsson, S., Lundin, E., Elgh, F., Ottander, U. & Idahl, A. (2020). Chlamydia trachomatis and Anti-MUC1 Serology and Subsequent Risk of High-Grade Serous Ovarian Cancer: A Population-Based Case-Control Study in Northern Sweden. Translational Oncology, 13(1), 86-91
Open this publication in new window or tab >>Chlamydia trachomatis and Anti-MUC1 Serology and Subsequent Risk of High-Grade Serous Ovarian Cancer: A Population-Based Case-Control Study in Northern Sweden
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2020 (English)In: Translational Oncology, ISSN 1944-7124, E-ISSN 1936-5233, Vol. 13, no 1, p. 86-91Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Chlamydia trachomatis salpingitis causes inflammatory damage to the fallopian tube and could potentially cause initiation and progression of high-grade serous ovarian cancer (HGSC). Furthermore, C. trachomatis infection may stimulate mucin 1 (MUC1) protein production, possibly affecting anti-MUC1 antibody levels. The aim of this study was to examine if serology indicating past infection with C. trachomatis as well as anti-MUC1 production was associated with subsequent risk of HGSC.

MATERIALS AND METHODS: In a prospective nested case-control study within the Northern Sweden Health and Disease Study and the Northern Sweden Maternity Cohort, the prevalence of chlamydial and anti-MUC1 antibodies was analyzed in blood samples drawn more than one year before diagnosis from 92 women with HGSC and 359 matched controls. Matching factors were age, date at blood draw, and sampling cohort. Plasma C. trachomatis IgG was analyzed using commercial micro-immunofluorescence test; chlamydial Heat Shock Protein 60 IgG (cHSP60) and anti-MUC1 IgG were analyzed with ELISA technique.

RESULTS: The prevalence of C. trachomatis IgG and cHSP60 IgG antibodies, as well as the level of anti-MUC1 IgG was similar in women with HGSC and controls (16.3% vs. 17.0%, P = 0.87; 27.2% vs. 28.5%, P = 0.80; median 0.24 vs. 0.25, P = 0.70). Anti-MUC1 IgG and cHSP60 IgG levels were correlated (r = 0.169; P < 0.001).

CONCLUSIONS: The findings of this prospective nested case-control study did not support an association between C. trachomatis infection, as measured by chlamydial serology, or anti-MUC1 IgG antibodies, and subsequent risk of HGSC.

Place, publisher, year, edition, pages
Elsevier, 2020
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:umu:diva-174272 (URN)10.1016/j.tranon.2019.09.007 (DOI)000502822300010 ()31805519 (PubMedID)2-s2.0-85075720208 (Scopus ID)
Available from: 2020-08-19 Created: 2020-08-19 Last updated: 2023-05-10Bibliographically approved
Israelsson, P., Dehlin, E., Nagaev, I., Lundin, E., Ottander, U. & Mincheva-Nilsson, L. (2020). Cytokine mRNA and protein expression by cell cultures of epithelial ovarian cancer: Methodological considerations on the choice of analytical method for cytokine analyses. American Journal of Reproductive Immunology, 84(1), Article ID e13249.
Open this publication in new window or tab >>Cytokine mRNA and protein expression by cell cultures of epithelial ovarian cancer: Methodological considerations on the choice of analytical method for cytokine analyses
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2020 (English)In: American Journal of Reproductive Immunology, ISSN 1046-7408, E-ISSN 1600-0897, Vol. 84, no 1, article id e13249Article in journal (Refereed) Published
Abstract [en]

Problem: To get a comprehensive picture of cytokine expression in health and disease is difficult, cytokines are transiently and locally expressed, and protein analyses are burdened by biological modifications, technical issues, and sensitivity to handling of samples. Thus, alternative methods, based on molecular techniques for cytokine mRNA analyses, are often used. We compared cytokine mRNA and protein expression to evaluate whether cytokine mRNA profiles can be used instead of protein analyses.

Method of study: In kinetic experiments, cytokine mRNA and protein expression of IL-1 beta, IL-6, IL-8, TNF-alpha, and TNF-beta/LTA were studied using real-time RT-qPCR and Luminex(R) microarrays in the ovarian cancer cell lines OVCAR-3, SKOV-3 and the T-cell line Jurkat, after activation of transcription by thermal stress. In addition, we analyzed IL-6 and IL-8 mRNA and protein in a small number of ovarian cancer patients.

Results: Ovarian cancer cells can express cytokines on both mRNA and protein level, with 1-4 hours' time delay between the mRNA and protein peak and a negative Spearman correlation. The mRNA and protein expression in patient samples was poorly correlated, reflecting previous studies.

Conclusion: Cytokine mRNA and protein expression levels show diverging results, depending on the material analyzed and the method used. Considering the high sensitivity and reproducibility of real-time RT-qPCR, we suggest that cytokine mRNA profiles could be used as a proxy for protein expression for some specific purposes, such as comparisons between different patient groups, and in defining mechanistic pathways involved in the pathogenesis of cancer and other pathological conditions.

Place, publisher, year, edition, pages
John Wiley & Sons, 2020
Keywords
cytokine, mRNA, ovarian cancer, protein, protein microarray, real-time polymerase chain reaction
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:umu:diva-171392 (URN)10.1111/aji.13249 (DOI)000530699700001 ()32307767 (PubMedID)2-s2.0-85085074930 (Scopus ID)
Available from: 2020-06-12 Created: 2020-06-12 Last updated: 2023-03-24Bibliographically approved
Yammine, S., Huybrechts, I., Biessy, C., Dossus, L., Aglago, E. K., Naudin, S., . . . Chajes, V. (2020). Dietary and Circulating Fatty Acids and Ovarian Cancer Risk in the European Prospective Investigation into Cancer and Nutrition. Cancer Epidemiology, Biomarkers and Prevention, 29(9), 1739-1749
Open this publication in new window or tab >>Dietary and Circulating Fatty Acids and Ovarian Cancer Risk in the European Prospective Investigation into Cancer and Nutrition
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2020 (English)In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 29, no 9, p. 1739-1749Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Philadelphia: American Association for Cancer Research, 2020
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-175456 (URN)10.1158/1055-9965.EPI-19-1477 (DOI)000566862600005 ()32616494 (PubMedID)2-s2.0-85100331509 (Scopus ID)
Available from: 2020-10-06 Created: 2020-10-06 Last updated: 2023-03-23Bibliographically approved
Björk, E., Vinnars, M.-T., Nagaev, I., Nagaeva, O., Lundin, E., Ottander, U. & Mincheva-Nilsson, L. (2020). Enhanced local and systemic inflammatory cytokine mRNA expression in women with endometriosis evokes compensatory adaptive regulatory mRNA response that mediates immune suppression and impairs cytotoxicity. American Journal of Reproductive Immunology, 84(4), Article ID e13298.
Open this publication in new window or tab >>Enhanced local and systemic inflammatory cytokine mRNA expression in women with endometriosis evokes compensatory adaptive regulatory mRNA response that mediates immune suppression and impairs cytotoxicity
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2020 (English)In: American Journal of Reproductive Immunology, ISSN 1046-7408, E-ISSN 1600-0897, Vol. 84, no 4, article id e13298Article in journal (Refereed) Published
Abstract [en]

Problem: Endometriosis is a disease characterized by ectopic implantation of endometrium and impaired immune responses. To explore its pathogenic mechanisms, we studied the local and systemic cytokine mRNA profiles and their role in the immunity of patients with endometriosis and healthy controls.

Method of Study: mRNA for eleven cytokines defining cytotoxic Th1, humoral Th2, regulatory Tr1/Th3, and inflammatory cytokine profiles was characterized locally in endometriotic tissue and endometrium, and systemically in PBMCs from women with endometriosis and healthy controls, using real‐time qRT‐PCR. In addition, immunohistochemical stainings with monoclonal antibodies were performed looking for T regulatory cells in endometriotic lesions.

Results: We found a downregulation of mRNA for cytokines mediating cytotoxicity and antibody response and an upregulation of inflammatory and T‐regulatory cytokines in the endometriotic tissues and endometrium from the patients with endometriosis, suggesting enhanced local inflammation and priming of an adaptive regulatory response. Consistent with those findings, there was an abundancy of T regulatory cells in the endometriotic lesions.

Conclusions: The ectopic implantation seen in endometriosis could be possible as a consequence of increased inflammation and priming of adaptive T regulatory cells, resulting in impaired cytotoxicity and enhanced immune suppression.

Place, publisher, year, edition, pages
John Wiley & Sons, 2020
Keywords
Cytokines, Cytotoxicity, Endometriosis, Immune suppression, Inflammation, Regulatory T-Lymphocytes
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:umu:diva-173755 (URN)10.1111/aji.13298 (DOI)000548188900001 ()32623813 (PubMedID)2-s2.0-85087896208 (Scopus ID)
Funder
Swedish Research Council, 18-20-345240311Swedish Cancer Society, CAN 2018/350Swedish Cancer Society, 18 07 17
Available from: 2020-07-31 Created: 2020-07-31 Last updated: 2023-03-23Bibliographically approved
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