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Walsh, N., Zhang, H., Hyland, P. L., Yang, Q., Mocci, E., Zhang, M., . . . Stolzenberg-Solomon, R. Z. (2019). Agnostic Pathway/Gene Set Analysis of Genome-Wide Association Data Identifies Associations for Pancreatic Cancer. Journal of the National Cancer Institute, 111(6), Article ID djy155.
Open this publication in new window or tab >>Agnostic Pathway/Gene Set Analysis of Genome-Wide Association Data Identifies Associations for Pancreatic Cancer
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2019 (English)In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 111, no 6, article id djy155Article in journal (Refereed) Published
Abstract [en]

Background: Genome-wide association studies (GWAS) identify associations of individual single-nucleotide polymorphisms (SNPs) with cancer risk but usually only explain a fraction of the inherited variability. Pathway analysis of genetic variants is a powerful tool to identify networks of susceptibility genes.

Methods: We conducted a large agnostic pathway-based meta-analysis of GWAS data using the summary-based adaptive rank truncated product method to identify gene sets and pathways associated with pancreatic ductal adenocarcinoma (PDAC) in 9040 cases and 12 496 controls. We performed expression quantitative trait loci (eQTL) analysis and functional annotation of the top SNPs in genes contributing to the top associated pathways and gene sets. All statistical tests were two-sided.

Results: We identified 14 pathways and gene sets associated with PDAC at a false discovery rate of less than 0.05. After Bonferroni correction (P ≤ 1.3 × 10-5), the strongest associations were detected in five pathways and gene sets, including maturity-onset diabetes of the young, regulation of beta-cell development, role of epidermal growth factor (EGF) receptor transactivation by G protein-coupled receptors in cardiac hypertrophy pathways, and the Nikolsky breast cancer chr17q11-q21 amplicon and Pujana ATM Pearson correlation coefficient (PCC) network gene sets. We identified and validated rs876493 and three correlating SNPs (PGAP3) and rs3124737 (CASP7) from the Pujana ATM PCC gene set as eQTLs in two normal derived pancreas tissue datasets.

Conclusion: Our agnostic pathway and gene set analysis integrated with functional annotation and eQTL analysis provides insight into genes and pathways that may be biologically relevant for risk of PDAC, including those not previously identified.

National Category
Clinical Medicine
Research subject
Oncology
Identifiers
urn:nbn:se:umu:diva-154571 (URN)10.1093/jnci/djy155 (DOI)30541042 (PubMedID)
Available from: 2018-12-19 Created: 2018-12-19 Last updated: 2019-02-20Bibliographically approved
Nichols, H. B., Schoemaker, M. J., Cai, J., Xu, J., Wright, L. B., Brook, M. N., . . . Sandler, D. P. (2019). Breast Cancer Risk After Recent Childbirth: A Pooled Analysis of 15 Prospective Studies. Annals of Internal Medicine, 170(1), 22-30
Open this publication in new window or tab >>Breast Cancer Risk After Recent Childbirth: A Pooled Analysis of 15 Prospective Studies
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2019 (English)In: Annals of Internal Medicine, ISSN 0003-4819, E-ISSN 1539-3704, Vol. 170, no 1, p. 22-30Article in journal (Refereed) Published
Abstract [en]

Background: Parity is widely recognized as protective for breast cancer, but breast cancer risk may be increased shortly after childbirth. Whether this risk varies with breastfeeding, family history of breast cancer, or specific tumor subtype has rarely been evaluated.

Objective: To characterize breast cancer risk in relation to recent childbirth.

Design: Pooled analysis of individual-level data from 15 prospective cohort studies.

Setting: The international Premenopausal Breast Cancer Collaborative Group.

Participants: Women younger than 55 years.

Measurements: During 9.6 million person-years of follow-up, 18 826 incident cases of breast cancer were diagnosed. Hazard ratios (HRs) and 95% CIs for breast cancer were calculated using Cox proportional hazards regression.

Results: Compared with nulliparous women, parous women had an HR for breast cancer that peaked about 5 years after birth (HR, 1.80 [95% CI, 1.63 to 1.99]) before decreasing to 0.77 (CI, 0.67 to 0.88) after 34 years. The association crossed over from positive to negative about 24 years after birth. The overall pattern was driven by estrogen receptor (ER)-positive breast cancer; no crossover was seen for ER-negative cancer. Increases in breast cancer risk after childbirth were pronounced when combined with a family history of breast cancer and were greater for women who were older at first birth or who had more births. Breastfeeding did not modify overall risk patterns.

Limitations: Breast cancer diagnoses during pregnancy were not uniformly distinguishable from early postpartum diagnoses. Data on human epidermal growth factor receptor 2 (HER2) oncogene overexpression were limited.

Conclusion: Compared with nulliparous women, parous women have an increased risk for breast cancer for more than 20 years after childbirth. Health care providers should consider recent childbirth a risk factor for breast cancer in young women.

Primary Funding Source: The Avon Foundation, the National Institute of Environmental Health Sciences, Breast Cancer Now and the UK National Health Service, and the Institute of Cancer Research.

Place, publisher, year, edition, pages
American College of Physicians, 2019
National Category
Surgery
Identifiers
urn:nbn:se:umu:diva-154575 (URN)10.7326/M18-1323 (DOI)000454685300008 ()30534999 (PubMedID)
Funder
NIH (National Institute of Health), UM1 CA176726NIH (National Institute of Health), UM1 CA186107NIH (National Institute of Health), UM1 CA164974NIH (National Institute of Health), R01 CA058420NIH (National Institute of Health), R01 CA092447NIH (National Institute of Health), P50 CA168504Swedish Research CouncilSwedish Cancer SocietyRegion SkåneVästerbotten County Council
Available from: 2018-12-19 Created: 2018-12-19 Last updated: 2019-02-11Bibliographically approved
Nilchian, A., Johansson, J., Ghalali, A., Travica Asanin, S., Santiago, A., Rosencrantz, O., . . . Fuxe, J. (2019). CXADR-Mediated Formation of an AKT Inhibitory Signalosome at Tight Junctions Controls Epithelial-Mesenchymal Plasticity in Breast Cancer.. Cancer Research, 79(1), 47-60
Open this publication in new window or tab >>CXADR-Mediated Formation of an AKT Inhibitory Signalosome at Tight Junctions Controls Epithelial-Mesenchymal Plasticity in Breast Cancer.
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2019 (English)In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 79, no 1, p. 47-60Article in journal (Refereed) Published
Abstract [en]

Tight junctions (TJ) act as hubs for intracellular signaling pathways controlling epithelial cell fate and function. Deregulation of TJ is a hallmark of epithelial-mesenchymal transition (EMT), which contributes to carcinoma progression and metastasis. However, the signaling mechanisms linking TJ to the induction of EMT are not understood. Here we identify a TJ-based signalosome, which controls AKT signaling and EMT in breast cancer. The coxsackie- and adenovirus receptor (CXADR), a TJ protein with an essential yet uncharacterized role in organogenesis and tissue homeostasis, was identified as a key component of the signalosome. CXADR regulated the stability and function of the phosphatases and AKT inhibitors PTEN and PHLPP2. Loss of CXADR led to hyper-activation of AKT and sensitized cells to TGF-β1-induced EMT. Conversely, restoration of CXADR stabilized PHLPP2 and PTEN, inhibited AKT, and promoted epithelial differentiation. Loss of CXADR in luminal A breast cancer correlated with loss of PHLPP2 and PTEN and poor prognosis. These results show that CXADR promotes the formation of an AKT-inhibitory signalosome at TJ and regulates epithelial-mesenchymal plasticity in breast cancer cells. Moreover, loss of CXADR might be used as a prognostic marker in luminal breast cancer.

Place, publisher, year, edition, pages
American Association for Cancer Research, 2019
National Category
Basic Medicine Cancer and Oncology Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-154580 (URN)10.1158/0008-5472.CAN-18-1742 (DOI)000454833400006 ()30385615 (PubMedID)
Funder
Swedish Research Council, 2017-03056Swedish Research Council, 2018-3114Swedish Cancer Society, CAN 2015/773
Available from: 2018-12-19 Created: 2018-12-19 Last updated: 2019-01-25Bibliographically approved
Javed, M. A., Beyer, G., Le, N., Vinci, A., Wong, H., Palmer, D., . . . Krug, S. (2019). Impact of intensified chemotherapy in metastatic pancreatic ductal adenocarcinoma (PDAC) in clinical routine in Europe. Pancreatology (Print), 19(1), 97-104
Open this publication in new window or tab >>Impact of intensified chemotherapy in metastatic pancreatic ductal adenocarcinoma (PDAC) in clinical routine in Europe
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2019 (English)In: Pancreatology (Print), ISSN 1424-3903, E-ISSN 1424-3911, Vol. 19, no 1, p. 97-104Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis. Gemcitabine is the standard chemotherapy for patients with metastatic pancreatic adenocarcinoma (MPA). Randomized clinical trials evaluating intensified chemotherapies including FOLFIRINOX and nab-paclitaxel plus gemcitabine (NAB+GEM) have shown improvement in survival. Here, we have evaluated the efficacy of intensified chemotherapy versus gemcitabine monotherapy in real-life settings across Europe.

METHODS: A retrospective multi-center study including 1056 MPA patients, between 2012 and 2015, from nine centers in UK, Germany, Italy, Hungary and the Swedish registry was performed. Follow-up was at least 12 months. Cox proportional Harzards regression was used for uni- and multivariable evaluation of prognostic factors.

RESULTS: Of 1056 MPA patients, 1030 (98.7%) were assessable for survival analysis. Gemcitabine monotherapy was the most commonly used regimen (41.3%), compared to FOLFIRINOX (n = 204, 19.3%), NAB+GEM (n = 81, 7.7%) and other gemcitabine- or 5-FU-based regimens (n = 335, 31.7%). The median overall survival (OS) was: FOLFIRINOX 9.9 months (95%CI 8.4-12.6), NAB+GEM 7.9 months (95%CI 6.2-10.0), other combinations 8.5 months (95%CI 7.7-9.3) and gemcitabine monotherapy 4.9 months (95%CI 4.4-5.6). Compared to gemcitabine monotherapy, any combination of chemotherapeutics improved the survival with no significant difference between the intensified regimens. Multivariable analysis showed an association between treatment center, male gender, inoperability at diagnosis and performance status (ECOG 1-3) with poor prognosis.

CONCLUSION: Gemcitabine monotherapy was predominantly used in 2012-2015. Intensified chemotherapy improved OS in comparison to gemcitabine monotherapy. In real-life settings, the OS rates of different treatment approaches are lower than shown in randomized phase III trials.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Intensified chemotherapy, Multicenter study, Pancreatic cancer
National Category
Surgery Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-154578 (URN)10.1016/j.pan.2018.10.003 (DOI)000456089400015 ()30529068 (PubMedID)
Available from: 2018-12-19 Created: 2018-12-19 Last updated: 2019-02-26Bibliographically approved
Gasull, M., Pumarega, J., Kiviranta, H., Rantakokko, P., Raaschou-Nielsen, O., Bergdahl, I., . . . Porta, M. (2019). Methodological issues in a prospective study on plasma concentrations of persistent organic pollutants and pancreatic cancer risk within the EPIC cohort. Environmental Research, 169, 417-433, Article ID S0013-9351(18)30609-1.
Open this publication in new window or tab >>Methodological issues in a prospective study on plasma concentrations of persistent organic pollutants and pancreatic cancer risk within the EPIC cohort
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2019 (English)In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 169, p. 417-433, article id S0013-9351(18)30609-1Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The use of biomarkers of environmental exposure to explore new risk factors for pancreatic cancer presents clinical, logistic, and methodological challenges that are also relevant in research on other complex diseases.

OBJECTIVES: First, to summarize the main design features of a prospective case-control study -nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort- on plasma concentrations of persistent organic pollutants (POPs) and pancreatic cancer risk. And second, to assess the main methodological challenges posed by associations among characteristics and habits of study participants, fasting status, time from blood draw to cancer diagnosis, disease progression bias, basis of cancer diagnosis, and plasma concentrations of lipids and POPs. Results from etiologic analyses on POPs and pancreatic cancer risk, and other analyses, will be reported in future articles.

METHODS: Study subjects were 1533 participants (513 cases and 1020 controls matched by study centre, sex, age at blood collection, date and time of blood collection, and fasting status) enrolled between 1992 and 2000. Plasma concentrations of 22 POPs were measured by gas chromatography - triple quadrupole mass spectrometry (GC-MS/MS). To estimate the magnitude of the associations we calculated multivariate-adjusted odds ratios by unconditional logistic regression, and adjusted geometric means by General Linear Regression Models.

RESULTS: There were differences among countries in subjects' characteristics (as age, gender, smoking, lipid and POP concentrations), and in study characteristics (as time from blood collection to index date, year of last follow-up, length of follow-up, basis of cancer diagnosis, and fasting status). Adjusting for centre and time of blood collection, no factors were significantly associated with fasting status. Plasma concentrations of lipids were related to age, body mass index, fasting, country, and smoking. We detected and quantified 16 of the 22 POPs in more than 90% of individuals. All 22 POPs were detected in some participants, and the smallest number of POPs detected in one person was 15 (median, 19) with few differences by country. The highest concentrations were found for p,p'-DDE, PCBs 153 and 180 (median concentration: 3371, 1023, and 810 pg/mL, respectively). We assessed the possible occurrence of disease progression bias (DPB) in eight situations defined by lipid and POP measurements, on one hand, and by four factors: interval from blood draw to index date, tumour subsite, tumour stage, and grade of differentiation, on the other. In seven of the eight situations results supported the absence of DPB.

CONCLUSIONS: The coexistence of differences across study centres in some design features and participant characteristics is of relevance to other multicentre studies. Relationships among subjects' characteristics and among such characteristics and design features may play important roles in the forthcoming analyses on the association between plasma concentrations of POPs and pancreatic cancer risk.

Keywords
Biomarkers, methods, Disease progression bias, Environmental epidemiology, Lipids, Pancreatic cancer, Persistent organic pollutants
National Category
Surgery
Identifiers
urn:nbn:se:umu:diva-154577 (URN)10.1016/j.envres.2018.11.027 (DOI)30529143 (PubMedID)
Available from: 2018-12-19 Created: 2018-12-19 Last updated: 2019-02-12Bibliographically approved
Schoemaker, M. J., Nichols, H. B., Wright, L. B., Brook, M. N., Jones, M. E., O'Brien, K. M., . . . Swerdlow, A. J. (2018). Association of body mass index and age With subsequent breast cancer risk in premenopausal women. JAMA Oncology, 4(11), Article ID e181771.
Open this publication in new window or tab >>Association of body mass index and age With subsequent breast cancer risk in premenopausal women
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2018 (English)In: JAMA Oncology, ISSN 2374-2437, E-ISSN 2374-2445, Vol. 4, no 11, article id e181771Article in journal (Refereed) Published
Abstract [en]

IMPORTANCE The association between increasing body mass index (BMI; calculated as wei ght in kilograms divided by height in meters squared) and risk of breast cancer is unique in cancer epidemiology in that a crossover effect exists, with risk reduction before and risk increase after menopause. The inverse association with premenopausal breast cancer risk is poorly characterized but might be important in the understanding of breast cancer causation.

OBJECTIVE To investigate the association of BMI with premenopausal breast cancer risk, in particular by age at BMI, attained age, risk factors for breast cancer, and tumor characteristics.

DESIGN, SETTING, AND PARTICIPANTS This multicenter analysis used pooled individual-level data from 758 592 premenopausal women from 19 prospective cohorts to estimate hazard ratios (HRs) of premenopausal breast cancer in association with BMI from ages 18 through 54 years using Cox proportional hazards regression analysis. Median follow-up was 9.3 years (interquartile range, 4.9-13.5 years) per participant, with 13 082 incident cases of breast cancer. Participants were recruited from January 1,1963, through December 31, 2013, and data were analyzed from September 1.2013, through December 31, 2017.

EXPOSURES Body mass index at ages 18 to 24, 25 to 34,35 to 44, and 45 to 54 years.

MAIN OUTCOMES AND MEASURES Invasive or in situ premenopausal breast cancer.

RESULTS Among the 758 592 premenopausal women (median age, 40.6 years; interquartile range, 35.2-45.5 years) included in the analysis, inverse linear associations of BMI with breast cancer risk were found that were stronger for BMI at ages 18 to 24 years (HR per 5 kg/m(2) [5.0-U] difference, 0.77; 95% CI, 0.73-0.80) than for BMI at ages 45 to 54 years (HR per 5.0-U difference, 0.88; 95% CI, 0.86-0.91). The inverse associations were observed even among nonoverweight women. There was a 4.2-fold risk gradient between the highest and lowest BMI categories (BMI >= 35.0 vs <17.0) at ages 18 to 24 years (HR, 0.24; 95% CI, 0.14-0.40). Hazard ratios did not appreciably vary by attained age or between strata of other breast cancer risk factors. Associations were stronger for estrogen receptor-positive and/or progesterone receptor-positive than for hormone receptor-negative breast cancer for BMI at every age group (eg, for BMI at age 18 to 24 years: HR per 5.0-U difference for estrogen receptor-positive and progesterone receptor-positive tumors, 0.76 [95% CI, 0.70-0.81] vs hormone receptor-negative tumors, 0.85 [95% CI: 0.76-0.95]); BMI at ages 25 to 54 years was not consistently associated with triple-negative or hormone receptor-negative breast cancer overall.

CONCLUSIONS AND RELEVANCE The results of this study suggest that increased adiposity is associated with a reduced risk of premenopausal breast cancer at a greater magnitude than previously shown and across the entire distribution of BMI. The strongest associations of risk were observed for BMI in early adulthood. Understanding the biological mechanisms underlying these associations could have important preventive potential.

Place, publisher, year, edition, pages
American Medical Assocation, 2018
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-154074 (URN)10.1001/jamaoncol.2018.1771 (DOI)000449559500002 ()29931120 (PubMedID)
Funder
Swedish Research CouncilSwedish Cancer SocietyRegion SkåneVästerbotten County Council
Available from: 2018-12-12 Created: 2018-12-12 Last updated: 2018-12-12Bibliographically approved
Honda, K., Katzke, V. A., Hüsing, A., Okaya, S., Shoji, H., Onidani, K., . . . Kaaks, R. (2018). CA19-9 and apolipoprotein-A2 isoforms as detection markers for pancreatic cancer: a prospective evaluation. International Journal of Cancer
Open this publication in new window or tab >>CA19-9 and apolipoprotein-A2 isoforms as detection markers for pancreatic cancer: a prospective evaluation
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2018 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215Article in journal (Refereed) Epub ahead of print
Abstract [en]

Recently, we identified unique processing patterns of apolipoprotein A2 (ApoA2) in patients with pancreatic cancer. Our study provides a first prospective evaluation of an ApoA2 isoform ("ApoA2-ATQ/AT"), alone and in combination with carbohydrate antigen 19-9 (CA19-9), as an early detection biomarker for pancreatic cancer. We performed ELISA measurements of CA19-9 and ApoA2-ATQ/AT in 156 patients with pancreatic cancer and 217 matched controls within the European EPIC cohort, using plasma samples collected up to 60 months prior to diagnosis. The detection discrimination statistics were calculated for risk scores by strata of lag-time. For CA19-9, in univariate marker analyses, C-statistics to distinguish future pancreatic cancer patients from cancer-free individuals were 0.80 for plasma taken ≤6 months before diagnosis, and 0.71 for >6-18 months; for ApoA2-ATQ/AT, C-statistics were 0.62, and 0.65, respectively. Joint models based on ApoA2-ATQ/AT plus CA19-9 significantly improved discrimination within >6-18 months (C = 0.74 vs. 0.71 for CA19-9 alone, p = 0.022) and ≤ 18 months (C = 0.75 vs. 0.74, p = 0.022). At 98% specificity, and for lag times of ≤6, >6-18 or ≤ 18 months, sensitivities were 57%, 36% and 43% for CA19-9 combined with ApoA2-ATQ/AT, respectively, vs. 50%, 29% and 36% for CA19-9 alone. Compared to CA19-9 alone, the combination of CA19-9 and ApoA2-ATQ/AT may improve detection of pancreatic cancer up to 18 months prior to diagnosis under usual care, and may provide a useful first measure for pancreatic cancer detection prior to imaging.

Keywords
CA19-9, apolipoprotein A2, early detection, isoforms, pancreatic cancer, prospective study
National Category
Surgery
Identifiers
urn:nbn:se:umu:diva-154581 (URN)10.1002/ijc.31900 (DOI)30259989 (PubMedID)
Available from: 2018-12-19 Created: 2018-12-19 Last updated: 2019-02-11
Winter, D. C. & Sund, M. (2018). Cancer surgery in the genomic era. British Journal of Surgery, 105(2), e12-e13
Open this publication in new window or tab >>Cancer surgery in the genomic era
2018 (English)In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 105, no 2, p. e12-e13Article in journal, Editorial material (Refereed) Published
Place, publisher, year, edition, pages
John Wiley & Sons, 2018
National Category
Surgery
Identifiers
urn:nbn:se:umu:diva-154585 (URN)10.1002/bjs.10806 (DOI)000429002100001 ()29341145 (PubMedID)
Note

Special Issue: SI

Available from: 2018-12-19 Created: 2018-12-19 Last updated: 2019-01-16Bibliographically approved
Ge, W., Clendenen, T. V., Afanasyeva, Y., Koenig, K. L., Agnoli, C., Brinton, L. A., . . . Zeleniuch-Jacquotte, A. (2018). Circulating anti-Müllerian hormone and breast cancer risk: a study in ten prospective cohorts. International Journal of Cancer, 142(11), 2215-2226
Open this publication in new window or tab >>Circulating anti-Müllerian hormone and breast cancer risk: a study in ten prospective cohorts
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2018 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 142, no 11, p. 2215-2226Article in journal (Refereed) Published
Abstract [en]

A strong positive association has been observed between circulating anti‐Müllerian hormone (AMH), a biomarker of ovarian reserve, and breast cancer risk in three prospective studies. Confirming this association is important because of the paucity of biomarkers of breast cancer risk in premenopausal women. We conducted a consortium study including ten prospective cohorts that had collected blood from premenopausal women. A nested case–control design was implemented within each cohort. A total of 2,835 invasive (80%) and in situ (20%) breast cancer cases were individually matched to controls (n = 3,122) on age at blood donation. AMH was measured using a high sensitivity enzyme‐linked immunoabsorbent assay. Conditional logistic regression was applied to the aggregated dataset. There was a statistically significant trend of increasing breast cancer risk with increasing AMH concentration (ptrend across quartiles <0.0001) after adjusting for breast cancer risk factors. The odds ratio (OR) for breast cancer in the top vs. bottom quartile of AMH was 1.60 (95% CI = 1.31–1.94). Though the test for interaction was not statistically significant (pinteraction = 0.15), the trend was statistically significant only for tumors positive for both estrogen receptor (ER) and progesterone receptor (PR): ER+/PR+: ORQ4–Q1 = 1.96, 95% CI = 1.46–2.64, ptrend <0.0001; ER+/PR−: ORQ4–Q1 = 0.82, 95% CI = 0.40–1.68, ptrend = 0.51; ER−/PR+: ORQ4–Q1 = 3.23, 95% CI = 0.48–21.9, ptrend = 0.26; ER−/PR−: ORQ4–Q1 = 1.15, 95% CI = 0.63–2.09, ptrend = 0.60. The association was observed for both pre‐ (ORQ4–Q1= 1.35, 95% CI = 1.05–1.73) and post‐menopausal (ORQ4–Q1 = 1.61, 95% CI = 1.03–2.53) breast cancer (pinteraction = 0.34). In this large consortium study, we confirmed that AMH is associated with breast cancer risk, with a 60% increase in risk for women in the top vs. bottom quartile of AMH.

What's new? To make informed decisions about screening and prevention, women need tools to accurately assess their breast cancer risk. Young women have few predictive biomarkers to look to; estrogen and progesterone are only weakly predictive before menopause. Anti-Müllerian hormone (AMH), which strongly correlates with age at menopause, may also correlate with breast cancer risk, according to some previous data. Here, the authors test this correlation by conducting nested case-control studies within ten different cohorts. They found that breast cancer risk increased along with increasing AMH concentration, confirming this hormone as a possible biomarker for breast cancer.

Place, publisher, year, edition, pages
Hoboken: John Wiley & Sons, 2018
Keywords
AMH, anti-Müllerian hormone, breast cancer, nested case-control study
National Category
Surgery Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-146526 (URN)10.1002/ijc.31249 (DOI)000429545800003 ()29315564 (PubMedID)
Available from: 2018-04-11 Created: 2018-04-11 Last updated: 2018-08-31Bibliographically approved
Holsti, M., Wanhainen, A., Lundin, C., Björck, M., Tegler, G., Svensson, J. & Sund, M. (2018). Circulating Vascular Basement Membrane Fragments are Associated with the Diameter of the Abdominal Aorta and Their Expression Pattern is Altered in AAA Tissue. European Journal of Vascular and Endovascular Surgery, 56(1), 110-118
Open this publication in new window or tab >>Circulating Vascular Basement Membrane Fragments are Associated with the Diameter of the Abdominal Aorta and Their Expression Pattern is Altered in AAA Tissue
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2018 (English)In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 56, no 1, p. 110-118Article in journal (Refereed) Published
Abstract [en]

Objective: Abdominal aortic aneurysm (AAA) is characterised by enhanced proteolytic activity, and extracellular matrix (ECM) remodelling in the vascular wall. Type IV and XVIII collagen/endostatin are structural proteins in vascular basement membrane (VBM), a specialised ECM structure. Here the association between plasma levels of these collagens with the aortic diameter and expansion rate is studied, and their expression in aortic tissue characterised. Methods: This was a retrospective population based cohort study. Type IV and XVIII collagen/endostatin were analysed in plasma by ELISA assay in 615 men, divided into three groups based on the aortic diameter: 1) normal aorta <= 25 mm, 2) sub-aneurysmal aorta (SAA) 26-29 mm, and 3) AAA >= 30 mm. Follow up data were available for 159 men. The association between collagen levels and aortic diameter at baseline, and with the expansion rate at follow up were analysed in ordinal logistic regression and linear regression models, controlling for common confounding factors. Tissue expression of the collagens was analysed in normal aorta (n = 6) and AAA (n = 6) by immunofluorescence. Results: Plasma levels of type XVIII collagen/endostatin (136 ng/mL [SD 29] in individuals with a normal aorta diameter, 154 ng/ml [SD 45] in SAA, and 162 ng/ml [SD 46] in AAA; p = .001) and type IV collagen (105 ng/mL [SD 42] normal aorta, 124 ng/ml [SD 46] SAA, and 127 ng/ml [SD 47] AAA; p = .037) were associated with a larger aortic diameter. A significant association was found between the baseline levels of type XVIII/endostatin and the aortic expansion rate (p = .035), but in the multivariable model, only the initial aortic diameter remained significantly associated with expansion (p = .005). Altered expression patterns of both collagens were observed in AAA tissue. Conclusion: Plasma levels of circulating type IV and XVIII collagen/endostatin increase with AAA diameter. The expression pattern of VBM proteins is altered in the aneurysm wall.

Place, publisher, year, edition, pages
Saunders Elsevier, 2018
Keywords
Abdominal aortic aneurysm, Collagen, Basement membrane, Extracellular matrix, Circulation
National Category
Surgery
Identifiers
urn:nbn:se:umu:diva-152282 (URN)10.1016/j.ejvs.2018.03.002 (DOI)000444270700019 ()29656960 (PubMedID)
Funder
Västerbotten County Council, VLL-582791Västerbotten County Council, VLL-680121Västerbotten County Council, VLL-764621Swedish Research Council, K2013-64X-2040607-3Swedish Heart Lung Foundation, 2012-0353
Available from: 2018-10-01 Created: 2018-10-01 Last updated: 2019-02-18Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-7516-9543

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