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Walsh, N., Zhang, H., Hyland, P. L., Yang, Q., Mocci, E., Zhang, M., . . . Stolzenberg-Solomon, R. Z. (2018). Agnostic Pathway/Gene Set Analysis of Genome-Wide Association Data Identifies Associations for Pancreatic Cancer.. Journal of the National Cancer Institute
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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2018 (English)In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105Article in journal (Refereed) Epub ahead of print
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: 2018-12-19
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
Nichols, H. B., Schoemaker, M. J., Cai, J., Xu, J., Wright, L. B., Brook, M. N., . . . Sandler, D. P. (2018). Breast Cancer Risk After Recent Childbirth: A Pooled Analysis of 15 Prospective Studies.. Annals of Internal Medicine
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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2018 (English)In: Annals of Internal Medicine, ISSN 0003-4819, E-ISSN 1539-3704Article in journal (Refereed) Epub ahead of print
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.

National Category
Surgery
Identifiers
urn:nbn:se:umu:diva-154575 (URN)10.7326/M18-1323 (DOI)30534999 (PubMedID)
Available from: 2018-12-19 Created: 2018-12-19 Last updated: 2018-12-19
Sund, M., 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: 2018-12-19
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: 2018-10-01Bibliographically approved
Nilchian, A., Johansson, J., Ghalali, A., Travica Asanin, S., Santiago, A., Rosencrantz, O., . . . Fuxe, J. (2018). CXADR-Mediated Formation of an AKT Inhibitory Signalosome at Tight Junctions Controls Epithelial-Mesenchymal Plasticity in Breast Cancer.. Cancer Research, Article ID canres.1742.2018.
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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2018 (English)In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, article id canres.1742.2018Article in journal (Refereed) Epub ahead of print
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.

National Category
Basic Medicine
Identifiers
urn:nbn:se:umu:diva-154580 (URN)10.1158/0008-5472.CAN-18-1742 (DOI)30385615 (PubMedID)
Available from: 2018-12-19 Created: 2018-12-19 Last updated: 2018-12-19
Del Chiaro, M., Besselink, M. G., Scholten, L., Bruno, M. J., Cahen, D. L., Gress, T. M., . . . Wusten, L. (2018). European evidence-based guidelines on pancreatic cystic neoplasms. Gut, 67(5), 789-804
Open this publication in new window or tab >>European evidence-based guidelines on pancreatic cystic neoplasms
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2018 (English)In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 67, no 5, p. 789-804Article in journal (Refereed) Published
Abstract [en]

Evidence-based guidelines on the management of pancreatic cystic neoplasms (PCN) are lacking. This guideline is a joint initiative of the European Study Group on Cystic Tumours of the Pancreas, United European Gastroenterology, European Pancreatic Club, European-African Hepato-Pancreato-Biliary Association, European Digestive Surgery, and the European Society of Gastrointestinal Endoscopy. It replaces the 2013 European consensus statement guidelines on PCN. European and non-European experts performed systematic reviews and used GRADE methodology to answer relevant clinical questions on nine topics (biomarkers, radiology, endoscopy, intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm (MCN), serous cystic neoplasm, rare cysts, (neo)adjuvant treatment, and pathology). Recommendations include conservative management, relative and absolute indications for surgery. A conservative approach is recommended for asymptomatic MCN and IPMN measuring < 40 mm without an enhancing nodule. Relative indications for surgery in IPMN include a main pancreatic duct (MPD) diameter between 5 and 9.9 mm or a cyst diameter >= 40 mm. Absolute indications for surgery in IPMN, due to the high-risk of malignant transformation, include jaundice, an enhancing mural nodule > 5 mm, and MPD diameter > 10 mm. Lifelong follow-up of IPMN is recommended in patients who are fit for surgery. The European evidence-based guidelines on PCN aim to improve the diagnosis and management of PCN.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2018
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:umu:diva-147291 (URN)10.1136/gutjnl-2018-316027 (DOI)000429733600004 ()29574408 (PubMedID)
Available from: 2018-05-28 Created: 2018-05-28 Last updated: 2018-06-09Bibliographically approved
Klein, A. P., Wolpin, B. M., Risch, H. A., Stolzenberg-Solomon, R. Z., Mocci, E., Zhang, M., . . . Amundadottir, L. T. (2018). Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer. Nature Communications, 9, Article ID 556.
Open this publication in new window or tab >>Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer
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2018 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 9, article id 556Article in journal (Refereed) Published
Abstract [en]

In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Here, we find significant evidence of a novel association at rs78417682 (7p12/TNS3, P = 4.35 x 10(-8)). Replication of 10 promising signals in up to 2737 patients and 4752 controls from the PANcreatic Disease ReseArch (PAN-DoRA) consortium yields new genome-wide significant loci: rs13303010 at 1p36.33 (NOC2L, P = 8.36 x 10(-14)), rs2941471 at 8q21.11 (HNF4G, P = 6.60 x 10(-10)), rs4795218 at 17q12 (HNF1B, P = 1.32 x 10(-8)), and rs1517037 at 18q21.32 (GRP, P = 3.28 x 10(-8)). rs78417682 is not statistically significantly associated with pancreatic cancer in PANDoRA. Expression quantitative trait locus analysis in three independent pancreatic data sets provides molecular support of NOC2L as a pancreatic cancer susceptibility gene.

Place, publisher, year, edition, pages
Nature Publishing Group, 2018
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-145138 (URN)10.1038/s41467-018-02942-5 (DOI)000424451300001 ()29422604 (PubMedID)
Available from: 2018-03-05 Created: 2018-03-05 Last updated: 2018-06-09Bibliographically approved
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Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-7516-9543

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