umu.sePublications
Change search
Link to record
Permanent link

Direct link
BETA
Pettersson-Kymmer, UlrikaORCID iD iconorcid.org/0000-0002-0557-9803
Alternative names
Publications (10 of 50) Show all publications
Eriksson, A. L., Böttiger, Y., Ekman, A., Reis, M., Persson, K., Pettersson-Kymmer, U. & Wallerstedt, S. M. (2019). Läkemedelsarbete behöver vara integrerat i klinisk utbildning: Att göra många läkemedelsgenomgångar ökar trygghet och reflektion över patientens behandling, visar enkätstudie. Läkartidningen, 116, Article ID FHCT.
Open this publication in new window or tab >>Läkemedelsarbete behöver vara integrerat i klinisk utbildning: Att göra många läkemedelsgenomgångar ökar trygghet och reflektion över patientens behandling, visar enkätstudie
Show others...
2019 (Swedish)In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 116, article id FHCTArticle in journal (Refereed) Published
Abstract [en]

A prerequisite for rational use of medicines is adequate prescribing skills; drug treatment is a complex task requiring diagnostic competence combined with pharmacologic knowledge and patient communication skills. Acquiring professional confidence in the art of prescribing is essential during medical training. The results of this questionnaire study, conducted in four medical schools in Sweden after the course in internal medicine (252 respondents; response rate: 74%; median age: 24 years, 61% female), show that 45% and 62% were confident in performing medication reviews and writing medication summary reports, respectively, i.e. the basics of prescribing. The confidence increased by the number of reviews and reports performed, i.e. the extent of practice (correlation coefficients: 0.41 and 0.38, respectively, both p<0.0001), as did the extent of the students' reflection on important aspects of drug treatment such as adherence, adverse reactions, renal function, dosing, and drug interactions. In multivariate regression analyses, major predictors for confidence in performing medication reviews were extent of practice and extent of clinical supervision. The results suggest that these factors are keys to acquiring professional confidence in the art of prescribing.

National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:umu:diva-162384 (URN)31192436 (PubMedID)
Note

[Preparing for the licence to prescribe in medical school: a questionnaire study on medical students professional confidence in the art of prescribing]

Available from: 2019-08-19 Created: 2019-08-19 Last updated: 2019-11-22Bibliographically approved
Trajanoska, K., Morris, J. A., Oei, L., Zheng, H.-F., Evans, D. M., Kiel, D. P., . . . Rivadeneira, F. (2018). Assessment of the genetic and clinical determinants of fracture risk: genome wide association and mendelian randomisation study. BMJ. British Medical Journal, 362, Article ID k3225.
Open this publication in new window or tab >>Assessment of the genetic and clinical determinants of fracture risk: genome wide association and mendelian randomisation study
Show others...
2018 (English)In: BMJ. British Medical Journal, E-ISSN 1756-1833, Vol. 362, article id k3225Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: To identify the genetic determinants of fracture risk and assess the role of 15 clinical risk factors on osteoporotic fracture risk.

DESIGN: Meta-analysis of genome wide association studies (GWAS) and a two-sample mendelian randomisation approach.

SETTING: 25 cohorts from Europe, United States, east Asia, and Australia with genome wide genotyping and fracture data.

PARTICIPANTS: A discovery set of 37 857 fracture cases and 227 116 controls; with replication in up to 147 200 fracture cases and 150 085 controls. Fracture cases were defined as individuals (>18 years old) who had fractures at any skeletal site confirmed by medical, radiological, or questionnaire reports. Instrumental variable analyses were performed to estimate effects of 15 selected clinical risk factors for fracture in a two-sample mendelian randomisation framework, using the largest previously published GWAS meta-analysis of each risk factor.

RESULTS: Of 15 fracture associated loci identified, all were also associated with bone mineral density and mapped to genes clustering in pathways known to be critical to bone biology (eg, SOST, WNT16, and ESR1) or novel pathways (FAM210A, GRB10, and ETS2). Mendelian randomisation analyses showed a clear effect of bone mineral density on fracture risk. One standard deviation decrease in genetically determined bone mineral density of the femoral neck was associated with a 55% increase in fracture risk (odds ratio 1.55 (95% confidence interval 1.48 to 1.63; P=1.5×10-68). Hand grip strength was inversely associated with fracture risk, but this result was not significant after multiple testing correction. The remaining clinical risk factors (including vitamin D levels) showed no evidence for an effect on fracture.

CONCLUSIONS: This large scale GWAS meta-analysis for fracture identified 15 genetic determinants of fracture, all of which also influenced bone mineral density. Among the clinical risk factors for fracture assessed, only bone mineral density showed a major causal effect on fracture. Genetic predisposition to lower levels of vitamin D and estimated calcium intake from dairy sources were not associated with fracture risk.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2018
National Category
Orthopaedics
Identifiers
urn:nbn:se:umu:diva-151426 (URN)10.1136/bmj.k3225 (DOI)000445701700002 ()30158200 (PubMedID)
Funder
NIH (National Institute of Health), N01AG-12100Swedish Research Council, K2010-54X-09894-19-3Swedish Research Council, 2006-3832Swedish Research Council, K2010-52X-20229-05-3Swedish Foundation for Strategic Research Torsten Söderbergs stiftelseRagnar Söderbergs stiftelseRegion Västra GötalandNIH (National Institute of Health), U01 AR45580NIH (National Institute of Health), U01 AR45614NIH (National Institute of Health), U01 AR45632NIH (National Institute of Health), U01 AR45647NIH (National Institute of Health), U01 AR45654NIH (National Institute of Health), U01 AR45583NIH (National Institute of Health), U01 AG18197NIH (National Institute of Health), U01-AG027810NIH (National Institute of Health), UL1 RR024140Wellcome trust, 101123Wellcome trust, 110141Wellcome trust, 094134Forte, Swedish Research Council for Health, Working Life and WelfareThe Kempe Foundations, JCK-1021Västerbotten County Council, SpjutspetsanslagVLL: 159: 33-2007
Available from: 2018-09-03 Created: 2018-09-03 Last updated: 2019-06-12Bibliographically approved
Pettersson-Kymmer, U., Hanson, A. L., Madeleine, M. M., Wang, S. S., Schwartz, S. M., Newell, F., . . . Leo, P. J. (2018). HLA and KIR Associations of Cervical Neoplasia. Journal of Infectious Diseases, 218(12), 2006-2015
Open this publication in new window or tab >>HLA and KIR Associations of Cervical Neoplasia
Show others...
2018 (English)In: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 218, no 12, p. 2006-2015Article in journal (Refereed) Published
Abstract [en]

Background: Cervical cancer is the fourth most common cancer in women, and we recently reported human leukocyte antigen (HLA) alleles showing strong associations with cervical neoplasia risk and protection. HLA ligands are recognised by killer immunoglobulin-like receptors (KIRs) expressed on a range of immune cell subsets, governing their proinflammatory activity. We hypothesized that the inheritance of particular HLA-KIR combinations would increase cervical neoplasia risk.

Methods: Here, we used HLA and KIR dosages imputed from SNP genotype data from 2,143 cervical neoplasia cases and 13,858 healthy controls of European decent.

Results: Four novel HLA alleles were identified in association with cervical neoplasia: HLA-DRB3*9901 (OR=1.24, P=2.49×10-9), HLA-DRB5*0101 (OR=1.29, P=2.26×10-8), HLA-DRB5*9901 (OR=0.77, P=1.90×10-9) and HLA-DRB3*0301 (OR=0.63, P=4.06×10-5), due to their linkage disequilibrium with known cervical neoplasia-associated HLA-DRB1 alleles. We also found homozygosity of HLA-C1 group alleles is a protective factor for HPV16-related cervical neoplasia (C1/C1, OR=0.79, P=0.005). This protective association was restricted to carriers of either KIR2DL2 (OR=0.67, P=0.00045) or KIR2DS2 (OR=0.69, P=0.0006).

Conclusions: Our findings suggest that HLA-C1 group alleles play a role in protecting against HPV16-related cervical neoplasia, mainly through a KIR-mediated mechanism.

Place, publisher, year, edition, pages
Oxford University Press, 2018
Keywords
Cervical neoplasia; human leukocyte antigens (HLA), killer immunoglobulin-like receptors (KIRs), HPV16-related cervical neoplasia
National Category
Medical and Health Sciences Medical Genetics
Identifiers
urn:nbn:se:umu:diva-151134 (URN)10.1093/infdis/jiy483 (DOI)000453672600018 ()30099516 (PubMedID)
Funder
Swedish Research CouncilSwedish Foundation for Strategic Research Ragnar Söderbergs stiftelseTorsten Söderbergs stiftelseThe Kempe Foundations, JCK-1021Västerbotten County Council
Available from: 2018-08-28 Created: 2018-08-28 Last updated: 2019-05-21Bibliographically approved
Benetou, V., Orfanos, P., Feskanich, D., Michaëlsson, K., Pettersson-Kymmer, U., Byberg, L., . . . Trichopoulou, A. (2018). Mediterranean diet and hip fracture incidence among older adults: the CHANCES project. Osteoporosis International, 29(7), 1591-1599
Open this publication in new window or tab >>Mediterranean diet and hip fracture incidence among older adults: the CHANCES project
Show others...
2018 (English)In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 29, no 7, p. 1591-1599Article in journal (Refereed) Published
Abstract [en]

The association between adherence to Mediterranean diet (MD) and hip fracture incidence is not yet established. In a diverse population of elderly, increased adherence to MD was associated with lower hip fracture incidence. Except preventing major chronic diseases, adhering to MD might have additional benefits in lowering hip fracture risk.

INTRODUCTION: Hip fractures constitute a major public health problem among older adults. Latest evidence links adherence to Mediterranean diet (MD) with reduced hip fracture risk, but still more research is needed to elucidate this relationship. The potential association of adherence to MD with hip fracture incidence was explored among older adults.

METHODS: A total of 140,775 adults (116,176 women, 24,599 men) 60 years and older, from five cohorts from Europe and the USA, were followed-up for 1,896,219 person-years experiencing 5454 hip fractures. Diet was assessed at baseline by validated, cohort-specific, food-frequency questionnaires, and hip fractures were ascertained through patient registers or telephone interviews/questionnaires. Adherence to MD was evaluated by a scoring system on a 10-point scale modified to be applied also to non-Mediterranean populations. In order to evaluate the association between MD and hip fracture incidence, cohort-specific hazard ratios (HR), adjusted for potential confounders, were estimated using Cox proportional-hazards regression and pooled estimates were subsequently derived implementing random-effects meta-analysis.

RESULTS: A two-point increase in the score was associated with a significant 4% decrease in hip fracture risk (pooled adjusted HR 0.96; 95% confidence interval (95% CI) 0.92-0.99, pheterogeneity = 0.446). In categorical analyses, hip fracture risk was lower among men and women with moderate (HR 0.93; 95% CI 0.87-0.99) and high (HR 0.94; 95% CI 0.87-1.01) adherence to the score compared with those with low adherence.

CONCLUSIONS: In this large sample of older adults from Europe and the USA, increased adherence to MD was associated with lower hip fracture incidence.

Place, publisher, year, edition, pages
Springer, 2018
Keywords
Aging, Bone health, CHANCES, Dietary patterns, Hip fractures, Mediterranean diet
National Category
Orthopaedics Geriatrics
Identifiers
urn:nbn:se:umu:diva-151008 (URN)10.1007/s00198-018-4517-6 (DOI)000437737800012 ()29656347 (PubMedID)2-s2.0-85045236820 (Scopus ID)
Available from: 2018-08-22 Created: 2018-08-22 Last updated: 2018-08-22Bibliographically approved
Papadimitriou, N., Tsilidis, K. K., Orfanos, P., Benetou, V., Ntzani, E. E., Soerjomataram, I., . . . Trichopoulou, A. (2017). Burden of hip fracture using disability-adjusted life-years: a pooled analysis of prospective cohorts in the CHANCES consortium. Lancet Public Health, 2(5), E239-E246
Open this publication in new window or tab >>Burden of hip fracture using disability-adjusted life-years: a pooled analysis of prospective cohorts in the CHANCES consortium
Show others...
2017 (English)In: Lancet Public Health, ISSN 2468-2667, Vol. 2, no 5, p. E239-E246Article in journal (Refereed) Published
Abstract [en]

Background: No studies have estimated disability-adjusted life-years (DALYs) lost due to hip fractures using real-life follow-up cohort data. We aimed to quantify the burden of disease due to incident hip fracture using DALYs in prospective cohorts in the CHANCES consortium, and to calculate population attributable fractions based on DALYs for specific risk factors.

Methods: We used data from six cohorts of participants aged 50 years or older at recruitment to calculate DALYs. We applied disability weights proposed by the National OsteoporosisFoundation and did a series of sensitivity analyses to examine the robustness of DALY estimates. We calculated population attributable fractions for smoking, body-mass index (BMI), physical activity, alcohol intake, type 2 diabetes and parity, use of hormone replacement therapy, and oral contraceptives in women. We calculated summary risk estimates across cohorts with pooled analysis and random-effects meta-analysis methods.

Findings: 223 880 men and women were followed up for a mean of 13 years (SD 6). 7724 (3·5%) participants developed an incident hip fracture, of whom 413 (5·3%) died as a result. 5964 DALYs (27 per 1000 individuals) were lost due to hip fractures, 1230 (20·6%) of which were in the group aged 75–79 years. 4150 (69·6%) DALYs were attributed to disability. Current smoking was the risk factor responsible for the greatest hip fracture burden (7·5%, 95% CI 5·2–9·7) followed by physical inactivity (5·5%, 2·1–8·5), history of diabetes (2·8%, 2·1–4·0), and low to average BMI (2·0%, 1·4–2·7), whereas low alcohol consumption (0·01–2·5 g per day) and high BMI had a protective effect.

Interpretation: Hip fracture can lead to a substantial loss of healthy life-years in elderly people. National public health policies should be strengthened to reduce hip fracture incidence and mortality. Primary prevention measures should be strengthened to prevent falls, and reduce smoking and a sedentary lifestyle.

National Category
Geriatrics
Identifiers
urn:nbn:se:umu:diva-145628 (URN)10.1016/S2468-2667(17)30046-4 (DOI)000425586300012 ()29253489 (PubMedID)
Available from: 2018-03-14 Created: 2018-03-14 Last updated: 2018-06-09Bibliographically approved
Leo, P. J., Madeleine, M. M., Wang, S., Schwartz, S. M., Newell, F., Pettersson-Kymmer, U., . . . Brown, M. A. (2017). Defining the genetic susceptibility to cervical neoplasia: A genome-wide association study. PLoS Genetics, 13(8), Article ID e1006866.
Open this publication in new window or tab >>Defining the genetic susceptibility to cervical neoplasia: A genome-wide association study
Show others...
2017 (English)In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 13, no 8, article id e1006866Article in journal (Refereed) Published
Abstract [en]

A small percentage of women with cervical HPV infection progress to cervical neoplasia, and the risk factors determining progression are incompletely understood. We sought to define the genetic loci involved in cervical neoplasia and to assess its heritability using unbiased unrelated case/control statistical approaches. We demonstrated strong association of cervical neoplasia with risk and protective HLA haplotypes that are determined by the amino-acids carried at positions 13 and 71 in pocket 4 of HLA-DRB1 and position 156 in HLA-B. Furthermore, 36% (standard error 2.4%) of liability of HPV-associated cervical pre-cancer and cancer is determined by common genetic variants. Women in the highest 10% of genetic risk scores have approximately >7.1% risk, and those in the highest 5% have approximately >21.6% risk, of developing cervical neoplasia. Future studies should examine genetic risk prediction in assessing the risk of cervical neoplasia further, in combination with other screening methods.

Keywords
cervical neoplasia, GWAS, HPV infection
National Category
Cancer and Oncology
Research subject
molecular medicine (genetics and pathology); Cancer Epidemiology
Identifiers
urn:nbn:se:umu:diva-139764 (URN)10.1371/journal.pgen.1006866 (DOI)000408763800004 ()28806749 (PubMedID)
Available from: 2017-09-21 Created: 2017-09-21 Last updated: 2019-05-21Bibliographically approved
Katsoulis, M., Benetou, V., Karapetyan, T., Feskanich, D., Grodstein, F., Pettersson-Kymmer, U., . . . Trichopoulou, A. (2017). Excess mortality after hip fracture in elderly persons from Europe and the USA: the CHANCES project. Journal of Internal Medicine, 281(3), 300-310
Open this publication in new window or tab >>Excess mortality after hip fracture in elderly persons from Europe and the USA: the CHANCES project
Show others...
2017 (English)In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 281, no 3, p. 300-310Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Hip fractures are associated with diminished quality of life and survival especially amongst the elderly.

OBJECTIVE: All-cause mortality after hip fracture was investigated to assess its magnitude.

METHODS: A total of 122 808 participants from eight cohorts in Europe and the USA were followed up for a mean of 12.6 years, accumulating 4273 incident hip fractures and 27 999 deaths. Incident hip fractures were assessed through telephone interviews/questionnaires or national inpatient/fracture registries, and causes of death were verified with death certificates. Cox proportional hazards models and the time-dependent variable methodology were used to assess the association between hip fracture and mortality and its magnitude at different time intervals after the injury in each cohort. We obtained the effect estimates through a random-effects meta-analysis.

RESULTS: Hip fracture was positively associated with increased all-cause mortality; the hazard ratio (HR) in the fully adjusted model was 2.12, 95% confidence interval (CI) 1.76-2.57, after adjusting for potential confounders. This association was stronger amongst men [HR: 2.39, 95% CI: 1.72-3.31] than amongst women [HR: 1.92, 95% CI: 1.54-2.39], although this difference was not significant. Mortality was higher during the first year after the hip fracture [HR: 2.78, 95% CI: 2.12-3.64], but it remained elevated without major fluctuations after longer time since hip fracture [HR (95% CI): 1.89 (1.50-2.37) after 1-4 years; 2.15 (1.81-2.55) after 4-8 years; 1.79 (1.57-2.05) after 8 or more years].

CONCLUSION: In this large population-based sample of older persons across eight cohorts, hip fracture was associated with excess short- and long-term all-cause mortality in both sexes.

Keywords
CHANCES, ageing, bone, hip fracture, mortality
National Category
Geriatrics
Identifiers
urn:nbn:se:umu:diva-133010 (URN)10.1111/joim.12586 (DOI)000394893800007 ()28093824 (PubMedID)
Funder
EU, European Research Council
Available from: 2017-03-28 Created: 2017-03-28 Last updated: 2019-05-21Bibliographically approved
Tsilidis, K. K., Papadimitriou, N., Capothanassi, D., Bamia, C., Benetou, V., Jenab, M., . . . Trichopoulou, A. (2016). Burden of Cancer in a Large Consortium of Prospective Cohorts in Europe. Journal of the National Cancer Institute, 108(10), Article ID djw127.
Open this publication in new window or tab >>Burden of Cancer in a Large Consortium of Prospective Cohorts in Europe
Show others...
2016 (English)In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 108, no 10, article id djw127Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Disability-adjusted life-years (DALYs) are an indicator of mortality, morbidity, and disability. We calculated DALYs for cancer in middle-aged and older adults participating in the Consortium on Health and Ageing Network of Cohorts in Europe and the United States (CHANCES) consortium.

METHODS: A total of 90 199 participants from five European cohorts with 10 455 incident cancers and 4399 deaths were included in this study. DALYs were calculated as the sum of the years of life lost because of premature mortality (YLLs) and the years lost because of disability (YLDs). Population-attributable fractions (PAFs) were also estimated for five cancer risk factors, ie, smoking, adiposity, physical inactivity, alcohol intake, and type II diabetes.

RESULTS: After a median follow-up of 12 years, the total number of DALYs lost from cancer was 34 474 (382 per 1000 individuals) with a similar distribution by sex. Lung cancer was responsible for the largest number of lost DALYs (22.9%), followed by colorectal (15.3%), prostate (10.2%), and breast cancer (8.7%). Mortality (81.6% of DALYs) predominated over disability. Ever cigarette smoking was the risk factor responsible for the greatest total cancer burden (24.0%, 95% confidence interval [CI] = 22.2% to 26.0%), followed by physical inactivity (4.9%, 95% CI = 0.8% to 8.1%) and adiposity (1.8%, 95% CI = 0.2% to 2.8%).

CONCLUSIONS: DALYs lost from cancer were substantial in this large European sample of middle-aged and older adults. Even if the burden of disease because of cancer is predominantly caused by mortality, some cancers have sizeable consequences for disability. Smoking remained the predominant risk factor for total cancer burden.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-120160 (URN)10.1093/jnci/djw127 (DOI)000386947400011 ()27154917 (PubMedID)
Available from: 2016-05-10 Created: 2016-05-10 Last updated: 2018-06-07Bibliographically approved
Benetou, V., Orfanos, P., Feskanich, D., Michaëlsson, K., Pettersson-Kymmer, U., Eriksson, S., . . . Trichopoulou, A. (2016). Fruit and Vegetable Intake and Hip Fracture Incidence in Older Men and Women: The CHANCES Project. Journal of Bone and Mineral Research, 31(9), 1743-1752
Open this publication in new window or tab >>Fruit and Vegetable Intake and Hip Fracture Incidence in Older Men and Women: The CHANCES Project
Show others...
2016 (English)In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 31, no 9, p. 1743-1752Article in journal (Refereed) Published
Abstract [en]

The role of fruit and vegetable intake in relation to fracture prevention during adulthood and beyond is not adequately understood. We investigated the potential association between fruit and vegetable intake and hip fracture incidence in a large sample of elderly from Europe and United States. A total of 142,018 individuals (among which 116,509 women), aged ≥60 years old, from five cohorts, were followed-up prospectively for 1,911,482 person-years accumulating 5,552 hip fractures. Fruit and vegetable intake was assessed by validated, cohort-specific, food-frequency questionnaires. Ηip fractures were ascertained through national patient registers or telephone interviews/questionnaires. Adjusted hazard ratios (HR) derived by Cox proportional-hazards regression were estimated for each cohort and subsequently pooled using random-effects meta-analysis. Intake of ≤ 1 servings/day of fruit and vegetables combined was associated with 39% higher hip fracture risk [pooled adjusted HR:1.39, 95% Confidence Intervals (CIs): 1.20, 1.58] in comparison to moderate intake (>3 and ≤5 servings/day) (pfor heterogeneity  = 0.505), whereas higher intakes (>5 servings/day) were not associated with lower risk in comparison to the same reference. Associations were more evident among women. We concluded that a daily intake of one or less servings of fruits and vegetables was associated with increased hip fracture risk in relation to moderate daily intakes. Older adults with such low fruit and vegetable consumption may benefit from raising their intakes to moderate amounts in order to reduce their hip fracture risk. 

Keywords
hip fracture,  fruits,  vegetables,  nutrition,  epidemiology
National Category
Nutrition and Dietetics Orthopaedics
Identifiers
urn:nbn:se:umu:diva-120161 (URN)10.1002/jbmr.2850 (DOI)000383718100016 ()27061845 (PubMedID)
Available from: 2016-05-10 Created: 2016-05-10 Last updated: 2018-06-07Bibliographically approved
Hemminki, K., Chen, B., Kumar, A., Melander, O., Manjer, J., Hallmans, G., . . . Försti, A. (2016). Germline genetics of cancer of unknown primary (CUP) and its specific subtypes. OncoTarget, 7(16), 22140-22149
Open this publication in new window or tab >>Germline genetics of cancer of unknown primary (CUP) and its specific subtypes
Show others...
2016 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 16, p. 22140-22149Article in journal (Refereed) Published
Abstract [en]

Cancer of unknown primary site (CUP) is a fatal cancer diagnosed through metastases at various organs. Little is known about germline genetics of CUP which appears worth of a search in view of reported familial associations in CUP. In the present study, samples from CUP patients were identified from 2 Swedish biobanks and a German clinical trial, totaling 578 CUP patients and 7628 regionally matched controls. Diagnostic data specified the organ where metastases were diagnosed. We carried out a genome-wide association study on CUP cases and controls. In the whole sample set, 6 loci reached an allelic p-value in the range of 10-7 and were supported by data from the three centers. Three associations were located next to non-coding RNA genes. rs2660852 flanked 5'UTR of LTA4H (leukotriene A4 hydrolase), rs477145 was intronic to TIAM1 (T-cell lymphoma invasion and metastases) and rs2835931 was intronic to KCNJ6 (potassium channel, inwardly rectifying subfamily J, member 6). In analysis of subgroups of CUP patients (smokers, non-smokers and CUP with liver metastases) genome-wide significant associations were noted. For patients with liver metastases associations on chromosome 6 and 11, the latter including a cluster of genes DHCR7 and NADSYN1, encoding key enzymes in cholesterol and NAD synthesis, and KRTAP5-7, encoding a keratin associated protein. This first GWAS on CUP provide preliminary evidence that germline genes relating to inflammation (LTA4H), metastatic promotion (TIAM1) in association with lipid metabolic disturbance (chromosome 11 cluster) may contribute to the risk of CUP.

Keywords
hidden primary cancer, SNP, genotype, germline genetics, genetic risk factors
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-119104 (URN)10.18632/oncotarget.7903 (DOI)000377705900082 ()26959888 (PubMedID)
Available from: 2016-04-11 Created: 2016-04-11 Last updated: 2018-08-31Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-0557-9803

Search in DiVA

Show all publications