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Ljuslinder, Ingrid
Publications (10 of 24) Show all publications
Chuang, S.-C., Boeing, H., Vollset, S. E., Midttun, O., Ueland, P. M., Bueno-de-Mesquita, B., . . . Aleksandrova, K. (2016). Cellular immune activity biomarker neopterin is associated hyperlipidemia: results from a large population-based study. Immunity & Ageing, 13, Article ID 5.
Open this publication in new window or tab >>Cellular immune activity biomarker neopterin is associated hyperlipidemia: results from a large population-based study
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2016 (English)In: Immunity & Ageing, ISSN 1742-4933, E-ISSN 1742-4933, Vol. 13, article id 5Article in journal (Refereed) Published
Abstract [en]

Background: Increased serum neopterin had been described in older age two decades ago. Neopterin is a biomarker of systemic adaptive immune activation that could be potentially implicated in metabolic syndrome (MetS). Measurements of waist circumference, triglycerides, high-density lipoprotein cholesterol (HDLC), systolic and diastolic blood pressure, glycated hemoglobin as components of MetS definition, and plasma total neopterin concentrations were performed in 594 participants recruited in the European Prospective Investigation into Cancer and Nutrition (EPIC).

Results: Higher total neopterin concentrations were associated with reduced HDLC (9.7 %, p < 0.01 for men and 9.2 %, p < 0.01 for women), whereas no association was observed with the rest of the MetS components as well as with MetS overall (per 10 nmol/L: OR = 1.42, 95 % CI = 0.85-2.39 for men and OR = 1.38, 95 % CI = 0.79-2.43).

Conclusions: These data suggest that high total neopterin concentrations are cross-sectionally associated with reduced HDLC, but not with overall MetS.

Keyword
Neopterin, Cell-mediated immunity, Metabolic syndrome
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-118392 (URN)10.1186/s12979-016-0059-y (DOI)000370838100001 ()
Available from: 2016-04-18 Created: 2016-03-18 Last updated: 2017-11-30Bibliographically approved
Aleksandrova, K., Chuang, S.-C., Boeing, H., Zuo, H., Tell, G. S., Pischon, T., . . . Vineis, P. (2015). A prospective study of the immune system activation biomarker neopterin and colorectal cancer risk. Journal of the National Cancer Institute, 107(4), Article ID djv010.
Open this publication in new window or tab >>A prospective study of the immune system activation biomarker neopterin and colorectal cancer risk
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2015 (English)In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 107, no 4, article id djv010Article in journal (Refereed) Published
Abstract [en]

Background: Neopterin may be relevant for colorectal cancer (CRC) development, as a biomarker of cellular immune activity exerting pleiotropic effects on cellular ageing, oxidative stress, and inflammation. So far, the association between prediagnostic neopterin and colon and rectal cancer risk has not been evaluated in human populations. Methods: A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition cohort using data on plasma concentrations of total neopterin (T-N, sum of neopterin and 7,8-dihydroneopterin) in 830 incident CRC case patients (561 colon and 269 rectal) matched within risk sets to 830 control participants. A subsequent replication study used data from the Hordaland Health Study, where 173 CRC case patients have been diagnosed among 6594 healthy participants over 12 years of follow-up. Results: After multivariable adjustment for a priori chosen CRC risk factors, a "U-shaped" association of T-N with CRC was revealed. Compared with the second quintile of the T-N distribution, the relative risks for the first, third, fourth, and fifth quintiles were 2.37 (95% CI = 1.66 to 3.39), 1.24 (95% CI = 0.87 to 1.77), 1.55 (95% CI = 1.08 to 2.22), and 2.31 (95% CI = 1.63 to 3.27), respectively. Replication of these associations within the Hordaland Health Study yielded similar results. No differences have been observed when the associations were explored by colon and rectal cancer site (two-sided P-difference = .87) and after excluding case patients diagnosed within the first four follow-up years. Conclusions: These novel findings provide evidence of the role of both suppressed and activated cell-mediated immunity as reflected by prediagnostic T-N concentrations in the development of CRC.

Place, publisher, year, edition, pages
Oxford University Press, 2015
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-105269 (URN)10.1093/jnci/djv010 (DOI)000355082500013 ()
Available from: 2015-06-22 Created: 2015-06-22 Last updated: 2017-12-04Bibliographically approved
Kreimer, A. R., Brennan, P., Kuhs, K. A. L., Waterboer, T., Clifford, G., Franceschi, S., . . . Johansson, M. (2015). Human Papillomavirus Antibodies and Future Risk of Anogenital Cancer: A Nested Case-Control Study in the European Prospective Investigation Into Cancer and Nutrition Study. Journal of Clinical Oncology, 33(8), 877-884.
Open this publication in new window or tab >>Human Papillomavirus Antibodies and Future Risk of Anogenital Cancer: A Nested Case-Control Study in the European Prospective Investigation Into Cancer and Nutrition Study
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2015 (English)In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 33, no 8, p. 877-884Article in journal (Refereed) Published
Abstract [en]

Purpose Human papillomavirus (HPV) type 16 (HPV16) causes cancer at several anatomic sites. In the European Prospective Investigation Into Cancer and Nutrition study, HPV16 E6 seropositivity was present more than 10 years before oropharyngeal cancer diagnosis and was nearly absent in controls. The current study sought to evaluate the extent to which HPV16 E6 antibodies are present before diagnosis of anogenital cancers within the same cohort. Methods Four hundred incident anogenital cancers (273 cervical, 24 anal, 67 vulvar, 12 vaginal, and 24 penile cancers) with prediagnostic blood samples (collected on average 3 and 8 years before diagnosis for cervix and noncervix cancers, respectively) and 718 matched controls were included. Plasma was analyzed for antibodies against HPV16 E6 and multiple other HPV proteins and genotypes and evaluated in relation to risk using unconditional logistic regression. Results HPV16 E6 seropositivity was present in 29.2% of individuals (seven of 24 individuals) who later developed anal cancer compared with 0.6% of controls (four of 718 controls) who remained cancer free (odds ratio [OR], 75.9; 95% CI, 17.9 to 321). HPV16 E6 seropositivity was less common for cancers of the cervix (3.3%), vagina (8.3%), vulva (1.5%), and penis (8.3%). No associations were seen for non-type 16 HPV E6 antibodies, apart from anti-HPV58 E6 and anal cancer (OR, 6.8; 95% CI, 1.4 to 33.1). HPV16 E6 seropositivity tended to increase in blood samples drawn closer in time to cancer diagnosis. Conclusion HPV16 E6 seropositivity is relatively common before diagnosis of anal cancer but rare for other HPV-related anogenital cancers.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-106032 (URN)10.1200/JCO.2014.57.8435 (DOI)000356055600014 ()25667279 (PubMedID)
Available from: 2015-07-06 Created: 2015-07-03 Last updated: 2017-12-04Bibliographically approved
Nimptsch, K., Aleksandrova, K., Boeing, H., Janke, J., Lee, Y.-A., Jenab, M., . . . Pischon, T. (2015). Plasma fetuin-A concentration, genetic variation in the AHSG gene and risk of colorectal cancer. International Journal of Cancer, 137(4), 911-920.
Open this publication in new window or tab >>Plasma fetuin-A concentration, genetic variation in the AHSG gene and risk of colorectal cancer
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2015 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 137, no 4, p. 911-920Article in journal (Refereed) Published
Abstract [en]

Fetuin-A, also referred to as alpha 2-Heremans-Schmid glycoprotein (AHSG), is a liver protein known to inhibit insulin actions. Hyperinsulinemia is a possible risk factor for colorectal cancer; however, the role of fetuin-A in the development of colorectal cancer is unclear. We investigated the association between circulating fetuin-A and colorectal cancer risk in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition. Fetuin-A concentrations were measured in prediagnostic plasma samples from 1,367 colorectal cancer cases and 1,367 matched controls. In conditional logistic regression models adjusted for potential confounders, the estimated relative risk (95% confidence interval) of colorectal cancer per 40 mg/mL higher fetuin-A concentrations (approximately one standard deviation) was 1.13 (1.02-1.24) overall, 1.21 (1.05-1.39) in men, 1.06 (0.93-1.22) in women, 1.13 (1.00-1.27) for colon cancer and 1.12 (0.94-1.32) for rectal cancer. To improve causal inference in a Mendelian Randomization approach, five tagging single nucleotide polymorphisms of the AHSG gene were genotyped in a subset of 456 case-control pairs. The AHSG allele-score explained 21% of the interindividual variation in plasma fetuin-A concentrations. In instrumental variable analysis, genetically raised fetuin-A was not associated with colorectal cancer risk (relative risk per 40 mg/mL genetically determined higher fetuin-A was 0.98, 95% confidence interval: 0.73-1.33). The findings of our study indicate a modest linear association between fetuin-A concentrations and risk of colorectal cancer but suggest that fetuin-A may not be causally related to colorectal cancer development.

Keyword
fetuin-A, AHSG, colorectal cancer
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-106308 (URN)10.1002/ijc.29448 (DOI)000356428400017 ()25611809 (PubMedID)
Available from: 2015-07-20 Created: 2015-07-10 Last updated: 2017-12-04Bibliographically approved
Hughes, D. J., Fedirko, V., Jenab, M., Schomburg, L., Méplan, C., Freisling, H., . . . Hesketh, J. E. (2015). Selenium status is associated with colorectal cancer risk in the European prospective investigation of cancer and nutrition cohort.. International Journal of Cancer, 136(5), 1149-1161.
Open this publication in new window or tab >>Selenium status is associated with colorectal cancer risk in the European prospective investigation of cancer and nutrition cohort.
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2015 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 136, no 5, p. 1149-1161Article in journal (Refereed) Published
Abstract [en]

Suboptimal intakes of the micronutrient selenium (Se) are found in many parts of Europe. Low Se status may contribute to colorectal cancer (CRC) development. We assessed Se status by measuring serum levels of Se and Selenoprotein P (SePP) and examined the association with CRC risk in a nested case-control design (966 CRC cases; 966 matched controls) within the European Prospective Investigation into Cancer and Nutrition. Se was measured by total reflection X-ray fluorescence and SePP by immunoluminometric sandwich assay. Multivariable incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. Respective mean Se and SePP levels were 84.0 μg/L and 4.3 mg/L in cases and 85.6 μg/L and 4.4 mg/L in controls. Higher Se concentrations were associated with a non-significant lower CRC risk (IRR = 0.92, 95% CI: 0.82-1.03 per 25 μg/L increase). However, sub-group analyses by sex showed a statistically significant association for women (ptrend  = 0.032; per 25 μg/L Se increase, IRR = 0.83, 95% CI: 0.70-0.97) but not for men. Higher SePP concentrations were inversely associated with CRC risk (ptrend  = 0.009; per 0.806 mg/L increase, IRR = 0.89, 95% CI: 0.82-0.98) with the association more apparent in women (ptrend  = 0.004; IRR = 0.82, 95% CI: 0.72-0.94 per 0.806 mg/L increase) than men (ptrend  = 0.485; IRR = 0.98, 95% CI: 0.86-1.12 per 0.806 mg/L increase). The findings indicate that Se status is suboptimal in many Europeans and suggest an inverse association between CRC risk and higher serum Se status, which is more evident in women.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-97466 (URN)10.1002/ijc.29071 (DOI)000346350500040 ()25042282 (PubMedID)
Available from: 2014-12-18 Created: 2014-12-18 Last updated: 2017-12-05Bibliographically approved
Aleksandrova, K., Jenab, M., Bueno-de-Mesquita, H. B., Fedirko, V., Kaaks, R., Lukanova, A., . . . Boeing, H. (2014). Biomarker patterns of inflammatory and metabolic pathways are associated with risk of colorectal cancer: results from the European Prospective Investigation into Cancer and Nutrition (EPIC). European Journal of Epidemiology, 29(4), 261-275.
Open this publication in new window or tab >>Biomarker patterns of inflammatory and metabolic pathways are associated with risk of colorectal cancer: results from the European Prospective Investigation into Cancer and Nutrition (EPIC)
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2014 (English)In: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 29, no 4, p. 261-275Article in journal (Refereed) Published
Abstract [en]

A number of biomarkers of inflammatory and metabolic pathways are individually related to higher risk of colorectal cancer (CRC); however, the association between biomarker patterns and CRC incidence has not been previously evaluated. Our study investigates the association of biomarker patterns with CRC in a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC). During median follow-up time of 7.0 (3.7-9.4) years, 1,260 incident CRC cases occurred and were matched to 1,260 controls using risk-set sampling. Pre-diagnostic measurements of C-peptide, glycated hemoglobin, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), C-reactive protein (CRP), reactive oxygen metabolites (ROM), insulin-like growth factor 1, adiponectin, leptin and soluble leptin receptor (sOB-R) were used to derive biomarker patterns from principal component analysis (PCA). The relation with CRC incidence was assessed using conditional logistic regression models. We identified four biomarker patterns 'HDL-C/Adiponectin fractions', 'ROM/CRP', 'TG/C-peptide' and 'leptin/sOB-R' to explain 60 % of the overall biomarker variance. In multivariable-adjusted logistic regression, the 'HDL-C/Adiponectin fractions', 'ROM/CRP' and 'leptin/sOB-R' patterns were associated with CRC risk [for the highest quartile vs the lowest, incidence rate ratio (IRR) = 0.69, 95 % CI 0.51-0.93, P-trend = 0.01; IRR = 1.70, 95 % CI 1.30-2.23, P-trend = 0.002; and IRR = 0.79, 95 % CI 0.58-1.07; P-trend = 0.05, respectively]. In contrast, the 'TG/C-peptide' pattern was not associated with CRC risk (IRR = 0.75, 95 % CI 0.56-1.00, P-trend = 0.24). After cases within the first 2 follow-up years were excluded, the 'ROM/CRP' pattern was no longer associated with CRC risk, suggesting potential influence of preclinical disease on these associations. By application of PCA, the study identified 'HDL-C/Adiponectin fractions', 'ROM/CRP' and 'leptin/sOB-R' as biomarker patterns representing potentially important pathways for CRC development.

Keyword
Colorectal cancer, Biomarker patterns, Inflammatory and metabolic pathways, Principal component analysis, European Prospective Investigation into Cancer and Nutrition (EPIC)
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-90866 (URN)10.1007/s10654-014-9901-8 (DOI)000336801600005 ()
Available from: 2014-07-08 Created: 2014-07-01 Last updated: 2017-12-05Bibliographically approved
Dik, V. K., Bueno-de-Mesquita, H. B., Van Oijen, M. G., Siersema, P. D., Uiterwaal, C. S., Van Gils, C. H., . . . Riboli, E. (2014). Coffee and tea consumption, genotype based CYP1A2 and NAT2 activity, and colorectal cancer risk: results from the EPIC cohort study. International Journal of Cancer, 135(2), 401-412.
Open this publication in new window or tab >>Coffee and tea consumption, genotype based CYP1A2 and NAT2 activity, and colorectal cancer risk: results from the EPIC cohort study
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2014 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 135, no 2, p. 401-412Article in journal (Refereed) Published
Abstract [en]

Coffee and tea contain numerous antimutagenic and antioxidant components and high levels of caffeine that may protect against colorectal cancer (CRC). We investigated the association between coffee and tea consumption and CRC risk and studied potential effect modification by CYP1A2 and NAT2 genotypes, enzymes involved in the metabolization of caffeine. Data from 477,071 participants (70.2% female) of the European Investigation into Cancer and Nutrition (EPIC) cohort study were analyzed. At baseline (1992-2000) habitual (total, caffeinated and decaffeinated) coffee and tea consumption was assessed with dietary questionnaires. Cox proportional hazards models were used to estimate adjusted hazard ratio's (HR) and 95%-confidence intervals (95%-CI). Potential effect modification by genotype-based CYP1A2 and NAT2 activity was studied in a nested case-control set of 1,252 cases and 2,175 controls. After a median follow-up of 11.6 years, 4,234 participants developed CRC (mean age 64.7±8.3 years). Total coffee consumption (high vs. non/low) was not associated with CRC risk (HR 1.06, 95%-CI 0.95-1.18) or subsite cancers, and no significant associations were found for caffeinated (HR 1.10, 95%-CI 0.97-1.26) and decaffeinated coffee (HR 0.96, 95%-CI 0.84-1.11) and tea (HR 0.97, 95%-CI 0.86-1.09). High coffee and tea consuming subjects with slow CYP1A2 or NAT2 activity had a similar CRC risk compared to non/low coffee and tea consuming subjects with a fast CYP1A2 or NAT2 activity, which suggest that caffeine metabolism does not affect the link between coffee and tea consumption and CRC risk. This study shows that coffee and tea consumption is not likely to be associated with overall CRC.

National Category
Public Health, Global Health, Social Medicine and Epidemiology Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-84217 (URN)10.1002/ijc.28655 (DOI)000335460400018 ()24318358 (PubMedID)
Available from: 2013-12-18 Created: 2013-12-18 Last updated: 2017-12-06Bibliographically approved
Aleksandrova, K., Pischon, T., Jenab, M., Bueno-de-Mesquita, H. B., Fedirko, V., Norat, T., . . . Boeing, H. (2014). Combined impact of healthy lifestyle factors on colorectal cancer: a large European cohort study. BMC Medicine, 12(1), 168.
Open this publication in new window or tab >>Combined impact of healthy lifestyle factors on colorectal cancer: a large European cohort study
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2014 (English)In: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 12, no 1, p. 168-Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Excess body weight, physical activity, smoking, alcohol consumption and certain dietary factors are individually related to colorectal cancer (CRC) risk; however, little is known about their joint effects. The aim of this study was to develop a healthy lifestyle index (HLI) composed of five potentially modifiable lifestyle factors - healthy weight, physical activity, non-smoking, limited alcohol consumption and a healthy diet, and to explore the association of this index with CRC incidence using data collected within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: In the EPIC cohort, a total of 347,237 men and women, 25- to 70-years old, provided dietary and lifestyle information at study baseline (1992 to 2000). Over a median follow-up time of 12 years, 3,759 incident CRC cases were identified. The association between a HLI and CRC risk was evaluated using Cox proportional hazards regression models and population attributable risks (PARs) have been calculated. RESULTS: After accounting for study centre, age, sex and education, compared with 0 or 1 healthy lifestyle factors, the hazard ratio (HR) for CRC was 0.87 (95% confidence interval (CI): 0.44 to 0.77) for two factors, 0.79 (95% CI: 0.70 to 0.89) for three factors, 0.66 (95% CI: 0.58 to 0.75) for four factors and 0.63 (95% CI: 0.54 to 0.74) for five factors; P-trend <0.0001. The associations were present for both colon and rectal cancers, HRs, 0.61 (95% CI: 0.50 to 0.74; P for trend <0.0001) for colon cancer and 0.68 (95% CI: 0.53 to 0.88; P-trend <0.0001) for rectal cancer, respectively (P-difference by cancer sub-site = 0.10). Overall, 16% of the new CRC cases (22% in men and 11% in women) were attributable to not adhering to a combination of all five healthy lifestyle behaviours included in the index. CONCLUSIONS: Combined lifestyle factors are associated with a lower incidence of CRC in European populations characterized by western lifestyles. Prevention strategies considering complex targeting of multiple lifestyle factors may provide practical means for improved CRC prevention.

Place, publisher, year, edition, pages
BioMed Central, 2014
Keyword
acrylamide, dietary questionnaires, haemoglobin adducts, biomarkers, smoking, measurement errors, lifestyle factors, combined impact, population attributable risks, colorectal cancer, European Prospective Investigation into Cancer and Nutrition (EPIC)
National Category
Public Health, Global Health, Social Medicine and Epidemiology Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-95215 (URN)10.1186/s12916-014-0168-4 (DOI)000344889900001 ()25319089 (PubMedID)
Available from: 2014-10-24 Created: 2014-10-24 Last updated: 2017-12-05Bibliographically approved
Olofsson, R., Ny, L., All-Ericsson, C., Sternby Eilard, M. S., Rizell, M., Cahlin, C., . . . Lindnér, P. (2014). Isolated hepatic perfusion as a treatment for uveal melanoma liver metastases (the SCANDIUM trial): study protocol for a randomized controlled trial. Trials, 15, 317.
Open this publication in new window or tab >>Isolated hepatic perfusion as a treatment for uveal melanoma liver metastases (the SCANDIUM trial): study protocol for a randomized controlled trial
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2014 (English)In: Trials, ISSN 1745-6215, E-ISSN 1745-6215, Vol. 15, p. 317-Article in journal (Refereed) Published
Abstract [en]

Background: Uveal melanoma is the most common primary intraocular malignancy in adults. Despite successful control of the primary tumor, metastatic disease will ultimately develop in approximately 50% of patients, with the liver being the most common site for metastases. The median survival for patients with liver metastases is between 6 and 12 months, and no treatment has in randomized trials ever been shown to prolong survival. A previous phase II trial using isolated hepatic perfusion (IHP) has suggested a 14-month increase in overall survival compared with a historic control group consisting of the longest surviving patients in Sweden during the same time period (26 versus 12 months). Methods/Design: This is the protocol for a multicenter phase III trial randomizing patients with isolated liver metastases of uveal melanoma to IHP or best alternative care (BAC). Inclusion criteria include liver metastases (verified by biopsy) and no evidence of extra-hepatic tumor manifestations by positron emission tomography-computed tomography (PET-CT). The primary endpoint is overall survival at 24 months, with secondary endpoints including response rate, progression-free survival, and quality of life. The planned sample size is 78 patients throughout five years. Discussion: Patients with isolated liver metastases of uveal melanoma origin have a short expected survival and no standard treatment option exists. This is the first randomized clinical trial to evaluate IHP as a treatment option with overall survival being the primary endpoint.

Keyword
Uveal melanoma, Liver metastases, Isolated hepatic perfusion, Regional treatment
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-93494 (URN)10.1186/1745-6215-15-317 (DOI)000340787700001 ()25106493 (PubMedID)
Note

Errata Trials (2015), 16, 334. DOI: 10.1186/s13063-015-0809-8

Available from: 2014-11-10 Created: 2014-09-23 Last updated: 2017-12-05Bibliographically approved
Thompson, P. A., Ljuslinder, I., Tsavachidis, S., Brewster, A., Sahin, A., Hedman, H., . . . Melin, B. S. (2014). Loss of LRIG1 Locus Increases Risk of Early and Late Relapse of Stage I/II Breast Cancer. Cancer Research, 74(11), 2928-2935.
Open this publication in new window or tab >>Loss of LRIG1 Locus Increases Risk of Early and Late Relapse of Stage I/II Breast Cancer
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2014 (English)In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 74, no 11, p. 2928-2935Article in journal (Refereed) Published
Abstract [en]

Gains and losses at chromosome 3p12-21 are common in breast tumors and associated with patient outcomes. We hypothesized that the LRIG1 gene at 3p14.1, whose product functions in ErbB-family member degradation, is a critical tumor modifier at this locus. We analyzed 971 stage I/II breast tumors using Affymetrix Oncoscan molecular inversion probe arrays that include 12 probes located within LRIG1. Copy number results were validated against gene expression data available in the public database. By partitioning the LRIG1 probes nearest exon 12/13, we confirm a breakpoint in the gene and show that gains and losses in the subregions differ by tumor and patient characteristics including race/ethnicity. In analyses adjusted for known prognostic factors, loss of LRIG1 was independently associated with risk of any relapse (HR, 1.90; 95% CI, 1.32-2.73), relapse >= 5 years (HR, 2.39; 95% CI, 1.31-4.36), and death (HR, 1.55; 95% CI, 1.11-2.16). Analyses of copy number across chromosome 3, as well as expression data from pooled, publicly available datasets, corroborated the hypothesis of an elevated and persistent risk among cases with loss of or low LRIG1. We concluded that loss/low expression of LRIG1 is an independent risk factor for breast cancer metastasis and death in stage I/II patients. Increased hazard in patients with loss/low LRIG1 persists years after diagnosis, suggesting that LRIG1 is acting as a critical suppressor of tumor metastasis and is an early clinical indicator of risk for late recurrences in otherwise low-risk patients.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-91143 (URN)10.1158/0008-5472.CAN-13-2112 (DOI)000337170600004 ()
Available from: 2014-07-17 Created: 2014-07-15 Last updated: 2017-12-05Bibliographically approved
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