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Rasmuson, Torgny
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Baltar, V. T., Xun, W. W., Johansson, M., Ferrari, P., Chuang, S.-C., Relton, C., . . . Vineis, P. (2013). A structural equation modelling approach to explore the role of B vitamins and immune markers in lung cancer risk. European Journal of Epidemiology, 28(8), 677-688
Open this publication in new window or tab >>A structural equation modelling approach to explore the role of B vitamins and immune markers in lung cancer risk
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2013 (English)In: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 28, no 8, p. 677-688Article in journal (Refereed) Published
Abstract [en]

The one-carbon metabolism (OCM) is considered key in maintaining DNA integrity and regulating gene expression, and may be involved in the process of carcinogenesis. Several B-vitamins and amino acids have been implicated in lung cancer risk, via the OCM directly as well as immune system activation. However it is unclear whether these factors act independently or through complex mechanisms. The current study applies structural equations modelling (SEM) to further disentangle the mechanisms involved in lung carcinogenesis. SEM allows simultaneous estimation of linear relations where a variable can be the outcome in one equation and the predictor in another, as well as allowing estimation using latent variables (factors estimated by correlation matrix). A large number of biomarkers have been analysed from 891 lung cancer cases and 1,747 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Four putative mechanisms in the OCM and immunity were investigated in relation to lung cancer risk: methionine-homocysteine metabolism, folate cycle, transsulfuration, and mechanisms involved in inflammation and immune activation, all adjusted for tobacco exposure. The hypothesized SEM model confirmed a direct and protective effect for factors representing methionine-homocysteine metabolism (p = 0.020) and immune activation (p = 0.021), and an indirect protective effect of folate cycle (p = 0.019), after adjustment for tobacco smoking. In conclusion, our results show that in the investigation of the involvement of the OCM, the folate cycle and immune system in lung carcinogenesis, it is important to consider complex pathways (by applying SEM) rather than the effects of single vitamins or nutrients (e.g. using traditional multiple regression). In our study SEM were able to suggest a greater role of the methionine-homocysteine metabolism and immune activation over other potential mechanisms.

Keywords
B vitamins, folate, methionine, lung cancer, immune markers, structural equation model
National Category
Occupational Health and Environmental Health
Identifiers
urn:nbn:se:umu:diva-80829 (URN)10.1007/s10654-013-9793-z (DOI)000324321700006 ()23532743 (PubMedID)
Available from: 2013-09-26 Created: 2013-09-26 Last updated: 2018-06-08Bibliographically approved
Papworth, K., Bergh, A., Grankvist, K., Ljungberg, B., Sandlund, J. & Rasmuson, T. (2013). Osteopontin but not parathyroid hormone-related protein predicts prognosis in human renal cell carcinoma. Acta Oncologica, 52(1), 159-165
Open this publication in new window or tab >>Osteopontin but not parathyroid hormone-related protein predicts prognosis in human renal cell carcinoma
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2013 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, no 1, p. 159-165Article in journal (Refereed) Published
Abstract [en]

Objective. To evaluate the relationship between osteopontin (OPN) in serum and plasma and parathyroid hormone-related protein (PTHrP) in serum, plasma and tumour tissue, and to assess the prognostic impact of OPN and PTHrP in human renal cell carcinoma (RCC).

Material and methods. The study included 269 patients with RCC. In 189 patients, immunohistochemical (IHC) PTHrP tumour tissue expression was evaluated, and OPN and PTHrP in serum were assessed. In 80 patients, plasma OPN and PTHrP were analysed. Tumour type, TNM stage, nuclear grade and RCC-specific survival were also registered. In a sub-group, IHC expression of CD 31 was assessed. The prognostic information of the factors was analysed using uni- and multivariate analyses.

Results. The median OPN level was 2.3 times higher in plasma than in serum. Serum OPN was significantly higher in patients with papillary RCC compared to clear cell RCC and chromophobe RCC. Both serum and plasma OPN levels were positively correlated to TNM stage and nuclear grade. Multivariate analysis showed that serum and plasma OPN levels were independent prognostic factors for RCC-specific survival, along with TNM stage. Immunohistochemical expression of PTHrP associated to TNM stage but not to nuclear grade or serum OPN. Furthermore, IHC expression of PTHrP was positively correlated to serum PTHrP but inversely to tumour CD31 expression. Plasma PTHrP was increased in 20% of the patients and related to TNM stage but not to nuclear grade. Plasma OPN was significantly higher in patients with increased PTHrP levels, compared to those with normal levels.

Conclusion. Plasma OPN levels differed between RCC types, and in clear cell RCC, both serum and plasma OPN levels were independent predictors of survival. We found no evidence for prognostic value related to circulating levels or the IHC expression of PTHrP.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-63418 (URN)10.3109/0284186X.2012.693623 (DOI)000312505900020 ()
Available from: 2013-01-03 Created: 2013-01-03 Last updated: 2018-06-08Bibliographically approved
Hoggart, C., Brennan, P., Tjönneland, A., Vogel, U., Overvad, K., Nautrup Östergaard, J., . . . Vineis, P. (2012). A Risk Model for Lung Cancer Incidence. Cancer Prevention Research, 5(6), 834-846
Open this publication in new window or tab >>A Risk Model for Lung Cancer Incidence
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2012 (English)In: Cancer Prevention Research, ISSN 1940-6207, E-ISSN 1940-6215, Vol. 5, no 6, p. 834-846Article in journal (Refereed) Published
Abstract [en]

Risk models for lung cancer incidence would be useful for prioritising individuals for screening and participation in clinical trials of chemoprevention. We present a risk model for lung cancer built using prospective cohort data from a general population which predicts individual incidence in a given time period.We build separate risk models for current and former smokers utilising 169,035 ever smokers from the multicentre European Prospective Investigation into Cancer and Nutrition (EPIC) and considered a model for never smokers. The data set was split into independent training and test sets. Lung cancer incidence was modelled using survival analysis, stratifying by age started smoking, and for former smokers, also smoking duration. Other risk factors considered were smoking intensity, ten occupational/environmental exposures previously implicated with lung cancer, and SNPs at two loci identified by genome-wide association studies of lung cancer. Individual risk in the test set was measured by the predicted probability of lung cancer incidence in the year preceding last follow-up time, predictive accuracy was measured by the area under the receiver operator characteristic curve (AUC).Utilising smoking information alone gave good predictive accuracy: the AUC and 95% confidence interval in ever smokers was 0.843 (0.810, 0.875), the Bach model applied to the same data gave an AUC of 0.775 (0.737, 0.813). Other risk factors had negligible effect on the AUC, including never smokers for whom prediction was poor.Our model is generalisable and straightforward to implement. Its accuracy can be attributed to its modelling of lifetime exposure to smoking.

Place, publisher, year, edition, pages
Philadelphia: American Association for Cancer Research, 2012
Keywords
Risk model, risk factors, lung cancer, cigarette smoke, cohort study
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-54431 (URN)10.1158/1940-6207.CAPR-11-0237 (DOI)000308222500004 ()22496387 (PubMedID)
Available from: 2012-04-26 Created: 2012-04-26 Last updated: 2018-06-08Bibliographically approved
Rinaldi, S., Lise, M., Clavel-Chapelon, F., Boutron-Ruault, M.-C., Guillas, G., Overvad, K., . . . Franceschi, S. (2012). Body size and risk of differentiated thyroid carcinomas: findings from the EPIC study. International Journal of Cancer, 131(6), E1004-E1014
Open this publication in new window or tab >>Body size and risk of differentiated thyroid carcinomas: findings from the EPIC study
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2012 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 131, no 6, p. E1004-E1014Article in journal (Refereed) Published
Abstract [en]

Results from case-control and prospective studies suggest a moderate positive association between obesity and height and differentiated thyroid carcinoma (TC). Little is known on the relationship between other measures of adiposity and differentiated TC risk. Here, we present the results of a study on body size and risk of differentiated TC based on a large European prospective study (EPIC). During follow-up, 508 incident cases of differentiated TC were identified in women, and 58 in men. 78% of cases were papillary TC. Cox proportional hazard models were used to estimate hazard ratios (HRs). In women, differentiated TC risk was significantly associated with body mass index (BMI, kg/m(2) ) (HR highest vs lowest quintile = 1.41, 95% CI: 1.03 - 1.94); height (HR = 1.61; 95% CI: 1.18 - 2.20); HR highest vs lowest tertile waist (HR = 1.34, 95% CI: 1.00 - 1.79) and waist-to-hip ratio (HR = 1.42, 95% CI: 1.05 - 1.91). The association with BMI was somewhat stronger in women below age 50. Corresponding associations for papillary TC were similar to those for all differentiated TC. In men the only body size factors significantly associated with differentiated TC were height (non linear), and leg length (HR highest vs lowest tertile = 3.03, 95% CI: 1.30 - 7.07). Our study lends further support to the presence of a moderate positive association between differentiated TC risk and overweight and obesity in women. The risk increase among taller individuals of both sexes suggests that some genetic characteristics or early environmental exposures may also be implicated in the etiology of differentiated TC.

Place, publisher, year, edition, pages
John Wiley & Sons, 2012
Keywords
body size, differentiated thyroid carcinoma, EPIC
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-54429 (URN)10.1002/ijc.27601 (DOI)000306735700016 ()22511178 (PubMedID)
Available from: 2012-04-26 Created: 2012-04-26 Last updated: 2018-06-08Bibliographically approved
Linseisen, J., Rohrmann, S., Bueno-de-Mesquita, B., Büchner, F. L., Boshuizen, H. C., Agudo, A., . . . Riboli, E. (2011). Consumption of meat and fish and risk of lung cancer: results from the European Prospective Investigation into Cancer and Nutrition.. Cancer Causes and Control, 22(6), 909-918
Open this publication in new window or tab >>Consumption of meat and fish and risk of lung cancer: results from the European Prospective Investigation into Cancer and Nutrition.
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2011 (English)In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 22, no 6, p. 909-918Article in journal (Refereed) Published
Abstract [en]

Evidence from case-control studies, but less so from cohort studies, suggests a positive association between meat intake and risk of lung cancer. Therefore, this association was evaluated in the frame of the European Prospective Investigation into Cancer and Nutrition, EPIC. Data from 478,021 participants, recruited from 10 European countries, who completed a dietary questionnaire in 1992-2000 were evaluated; 1,822 incident primary lung cancer cases were included in the present evaluation. Relative risk estimates were calculated for categories of meat intake using multi-variably adjusted Cox proportional hazard models. In addition, the continuous intake variables were calibrated by means of 24-h diet recall data to account for part of the measurement error. There were no consistent associations between meat consumption and the risk of lung cancer. Neither red meat (RR = 1.06, 95% CI 0.89-1.27 per 50 g intake/day; calibrated model) nor processed meat (RR = 1.13, 95% CI 0.95-1.34 per 50 g/day; calibrated model) was significantly related to an increased risk of lung cancer. Also, consumption of white meat and fish was not associated with the risk of lung cancer. These findings do not support the hypothesis that a high intake of red and processed meat is a risk factor for lung cancer.

Place, publisher, year, edition, pages
Springer, 2011
Keywords
Lung cancer, Diet, Epidemiology, Meat, Fish, EPIC
Identifiers
urn:nbn:se:umu:diva-45260 (URN)10.1007/s10552-011-9764-1 (DOI)21479828 (PubMedID)
Available from: 2011-06-29 Created: 2011-06-29 Last updated: 2018-06-08Bibliographically approved
Timofeeva, M. N., McKay, J. D., Smith, G. D., Johansson, M., Byrnes, G. B., Chabrier, A., . . . Brennan, P. (2011). Genetic polymorphisms in 15q25 and 19q13 loci, cotinine levels, and risk of lung cancer in EPIC. Cancer Epidemiology, Biomarkers and Prevention, 20(10), 2250-2261
Open this publication in new window or tab >>Genetic polymorphisms in 15q25 and 19q13 loci, cotinine levels, and risk of lung cancer in EPIC
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2011 (English)In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 20, no 10, p. 2250-2261Article in journal (Refereed) Published
Abstract [en]

Backgrounds: Multiple polymorphisms affecting smoking behavior have been identified through genome-wide association studies. Circulating levels of the nicotine metabolite cotinine is a marker of recent smoking exposure. Hence, genetic variants influencing smoking behavior are expected to be associated with cotinine levels.METHODS: We conducted an analysis in a lung cancer case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. We investigated the effects of single-nucleotide polymorphisms (SNP) previously associated with smoking behavior on (i) circulating cotinine and (ii) lung cancer risk. A total of 894 cases and 1,805 controls were analyzed for cotinine and genotyped for 10 polymorphisms on 7p14, 8p11, 10q23, 15q25, and 19q13.RESULTS: Two variants in the nicotinic acetylcholine receptor subunit genes CHRNA5 and CHRNA3 on 15q25, rs16969968 and rs578776, were associated with cotinine (P = 0.001 and 0.03, respectively) in current smokers and with lung cancer risk (P < 0.001 and P = 0.001, respectively). Two 19q13 variants, rs7937 and rs4105144, were associated with increased cotinine (P = 0.003 and P < 0.001, respectively) but decreased lung cancer risk (P = 0.01 for both, after adjusting for cotinine). Variants in 7p14, 8p11, and 10q23 were not associated with cotinine or lung cancer risk.CONCLUSIONS: 15q25 and 19q13 SNPs were associated with circulating cotinine. The directions of association for 15q25 variants with cotinine were in accordance with that expected of lung cancer risk, whereas SNPs on 19q13 displayed contrasting associations of cotinine and lung cancer that require further investigation.Impact: This study is the largest to date investigating the effects of polymorphisms affecting smoking behavior on lung cancer risk using circulating cotinine measures as proxies for recent smoking behavior. Cancer Epidemiol Biomarkers Prev; ©2011 AACR.

National Category
Medical and Health Sciences
Research subject
Oncology; Nutrition
Identifiers
urn:nbn:se:umu:diva-47540 (URN)10.1158/1055-9965.EPI-11-0496 (DOI)21862624 (PubMedID)
Available from: 2011-09-22 Created: 2011-09-22 Last updated: 2018-06-08Bibliographically approved
Xun, W. W., Brennan, P., Tjonneland, A., Vogel, U., Overvad, K., Kaaks, R., . . . Vineis, P. (2011). Single-nucleotide polymorphisms (5p15.33, 15q25.1, 6p22.1, 6q27 and 7p15.3) and lung cancer survival in the European Prospective Investigation into Cancer and Nutrition (EPIC).. Mutagenesis, 26(5), 657-666
Open this publication in new window or tab >>Single-nucleotide polymorphisms (5p15.33, 15q25.1, 6p22.1, 6q27 and 7p15.3) and lung cancer survival in the European Prospective Investigation into Cancer and Nutrition (EPIC).
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2011 (English)In: Mutagenesis, ISSN 0267-8357, E-ISSN 1464-3804, Vol. 26, no 5, p. 657-666Article in journal (Refereed) Published
Abstract [en]

The single-nucleotide polymorphisms (SNPs) rs402710 (5p15.33), rs16969968 and rs8034191 (15q25.1) have been consistently identified by genome-wide association studies (GWAS) as significant predictors of lung cancer risk, while rs4324798 (6p22.1) was previously found to influence survival time in small-cell lung cancer (SCLC) patients. Using the same population of one of the original GWAS, we investigated whether the selected SNPs and 31 others (also identified in GWAS) influence survival time, assuming an additive model. The effect of each polymorphism on all cause survival was estimated in 1094 lung cancer patients, and lung cancer-specific survival in 763 patients, using Cox regression adjusted for a priori confounders and competing causes of death where appropriate. Overall, after 1558 person-years of post-diagnostic follow-up, 874 deaths occurred from all causes, including 690 from lung cancer. In the lung cancer-specific survival analysis (1102 person-years), only rs7452888 (6q27) and rs2710994 (7p15.3) modified survival, with adjusted hazard ratios of 1.19 (P = 0.009) and 1.32 (P = 0.011) respectively, taking competing risks into account. Some weak associations were identified in subgroup analysis for rs16969968 and rs8034191 (15q25.1) and rs4324798 (6p22.1) and survival in never-smokers, as well as for rs402710 in current smokers and SCLC patients. In conclusion, rs402710 (5p15.33), rs16969968 and rs8034191 (both 15q25.1) and rs4324798 (6p22.1) were found to be unrelated to survival times in this large cohort of lung cancer patients, regardless of whether the cause of death was from lung cancer or not. However, rs7452888 (6q27) was identified as a possible candidate SNP to influence lung cancer survival, while stratified analysis hinted at a possible role for rs8034191, rs16969968 (15q25.1) and rs4324798 (6p22.1) in influencing survival time in lung cancer patients who were never-smokers, based on a small sample.

National Category
Genetics
Identifiers
urn:nbn:se:umu:diva-47537 (URN)10.1093/mutage/ger030 (DOI)21750227 (PubMedID)
Available from: 2011-09-22 Created: 2011-09-22 Last updated: 2018-06-08Bibliographically approved
Baltar, V. T., Xun, W. W., Chuang, S.-C., Relton, C., Ueland, P. M., Vollset, S. E., . . . Vineis, P. (2011). Smoking, secondhand smoke, and cotinine levels in a subset of EPIC cohort. Cancer Epidemiology, Biomarkers and Prevention, 20(5), 869-875
Open this publication in new window or tab >>Smoking, secondhand smoke, and cotinine levels in a subset of EPIC cohort
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2011 (English)In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 20, no 5, p. 869-875Article in journal (Refereed) Published
Abstract [en]

Background: Several countries are discussing new legislation regarding the ban on smoking in public places, based on the growing evidence of the hazards of secondhand smoke (SHS) exposure. The objective of the present study is to quantitatively assess the relationship between smoking, SHS, and serum cotinine levels in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

Methods: From a study on lung cancer in the EPIC cohort, questionnaire information on smoking was collected at enrolment, and cotinine was measured in serum. Three statistical models were applied by using samples available in a cross-section design: (i) cotinine levels by categories combining smoking and SHS (n = 859); (ii) the effect of hours of passive smoking exposure in nonsmokers only (n = 107); (iii) the effect of the number of cigarettes consumed per day in current smokers only (n = 832). All models were adjusted for country, sex, age, and body mass index.

Results: Among nonsmokers, passive smokers presented significant differences in cotinine compared with nonexposed, with a marked (but not significant) difference among former-smokers. A one hour per day increment of SHS gave rise to a significant 2.58 nmol/L (0.45 ng/mL) increase in mean serum cotinine (P < 0.001). In current smokers, a one cigarette per day increment gave rise to a significant 22.44 nmol/L (3.95 ng/mL) increase in cotinine mean (P < 0.001).

Conclusions: There is clear evidence that not only tobacco smoking but also involuntary exposure increases cotinine levels.

Impact: This study strengthens the evidence for the benefits of a smoking ban in public places.

Place, publisher, year, edition, pages
American Association for Cancer Research, 2011
Identifiers
urn:nbn:se:umu:diva-45261 (URN)10.1158/1055-9965.EPI-10-1235 (DOI)21357382 (PubMedID)
Available from: 2011-06-29 Created: 2011-06-29 Last updated: 2018-06-08Bibliographically approved
Büchner, F. L., Bueno-de-Mesquita, H. B., Linseisen, J., Boshuizen, H. C., Kiemeney, L. A., Ros, M. M., . . . Riboli, E. (2010). Fruits and vegetables consumption and the risk of histological subtypes of lung cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC). Cancer Causes and Control, 21(3), 357-371
Open this publication in new window or tab >>Fruits and vegetables consumption and the risk of histological subtypes of lung cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)
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2010 (English)In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 21, no 3, p. 357-371Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: To examine the association between fruit and vegetable consumption and risk of different histological subtypes of lung cancer among participants of the European Prospective Investigation into Cancer and Nutrition study. METHODS: Multivariable Cox proportional hazard models were used to analyze the data. A calibration study in a subsample was used to reduce dietary measurement errors. RESULTS: During a mean follow-up of 8.7 years, 1,830 incident cases of lung cancer (574 adenocarcinoma, 286 small cell, 137 large cell, 363 squamous cell, 470 other histologies) were identified. In line with our previous conclusions, we found that after calibration a 100 g/day increase in fruit and vegetables consumption was associated with a reduced lung cancer risk (HR 0.94; 95% CI 0.89-0.99). This was also seen among current smokers (HR 0.93; 95% CI 0.90-0.97). Risks of squamous cell carcinomas in current smokers were reduced for an increase of 100 g/day of fruit and vegetables combined (HR 0.85; 95% CI 0.76-0.94), while no clear effects were seen for the other histological subtypes. CONCLUSION: We observed inverse associations between the consumption of vegetables and fruits and risk of lung cancer without a clear effect on specific histological subtypes of lung cancer. In current smokers, consumption of vegetables and fruits may reduce lung cancer risk, in particular the risk of squamous cell carcinomas.

Keywords
fruits, vegetables, lung neioplasms, small cell lung carcinoma, non-small-cell lung carcinoma, adenocarcinoma, large cell carcinoma
Identifiers
urn:nbn:se:umu:diva-34563 (URN)10.1007/s10552-009-9468-y (DOI)19924549 (PubMedID)
Available from: 2010-06-08 Created: 2010-06-08 Last updated: 2018-06-08Bibliographically approved
Norberg, L., Johansson, R. & Rasmuson, T. (2010). Intracranial tumours after external fractionated radiotherapy for pituitary adenomas in northern Sweden. Acta Oncologica, 49(8), 1276-1282
Open this publication in new window or tab >>Intracranial tumours after external fractionated radiotherapy for pituitary adenomas in northern Sweden
2010 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 49, no 8, p. 1276-1282Article in journal (Refereed) Published
Abstract [en]

The results indicate an increased risk of second primary intracranial tumours in patients treated with radiotherapy for pituitary adenomas, compared to patients not exposed to irradiation and to the general population. Meningiomas were more frequent than gliomas and the median time interval between radiotherapy and second intracranial tumour was 17 years.

Keywords
2nd brain-tumor; radiation-therapy; conservative surgery; nervous-system; follow-up; risk; mortality; macroadenomas; epidemiology; prevalence
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-39278 (URN)10.3109/02841861003782025 (DOI)000283065400010 ()20429723 (PubMedID)
Available from: 2011-01-20 Created: 2011-01-20 Last updated: 2018-06-08Bibliographically approved
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