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      Cancer incidence among children and young adults who have undergone x-ray guided cardiac catheterization procedures

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          Abstract

          Children and young adults with heart disease appear to be at increased risk of developing cancer, although the reasons for this are unclear. A cohort of 11,270 individuals, who underwent cardiac catheterizations while aged ≤ 22 years in the UK, was established from hospital records. Radiation doses from cardiac catheterizations and CT scans were estimated. The cohort was matched with the NHS Central Register and NHS Transplant Registry to determine cancer incidence and transplantation status. Standardized incidence ratios (SIR) with associated confidence intervals (CI) were calculated. The excess relative risk (ERR) of lymphohaematopoietic  neoplasia was also calculated using Poisson regression. The SIR was raised for all malignancies (2.32, 95% CI 1.65, 3.17), lymphoma (8.34, 95% CI 5.22, 12.61) and leukaemia (2.11, 95% CI 0.82, 4.42). After censoring transplant recipients, post-transplant, the SIR was reduced to 0.90 (95% CI 0.49, 1.49) for all malignancies. All lymphomas developed post-transplant. The SIR for all malignancies developing 5 years from the first cardiac catheterization (2 years for leukaemia/lymphoma) remained raised (3.01, 95% CI 2.09, 4.19) but was again reduced after censoring transplant recipients (0.98, 95% CI 0.48, 1.77). The ERR per mGy bone marrow dose for lymphohaematopoietic neoplasia was reduced from 0.541 (95% CI 0.104, 1.807) to 0.018 (95% CI − 0.002, 0.096) where transplantation status was accounted for as a time-dependent background risk factor. In conclusion, transplantation appears to be a large contributor to elevated cancer rates in this patient group. This is likely to be mainly due to associated immunosuppression, however, radiation exposure may also be a contributing factor.

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          Most cited references23

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          Studies of the mortality of atomic bomb survivors, Report 14, 1950-2003: an overview of cancer and noncancer diseases.

          This is the 14th report in a series of periodic general reports on mortality in the Life Span Study (LSS) cohort of atomic bomb survivors followed by the Radiation Effects Research Foundation to investigate the late health effects of the radiation from the atomic bombs. During the period 1950-2003, 58% of the 86,611 LSS cohort members with DS02 dose estimates have died. The 6 years of additional follow-up since the previous report provide substantially more information at longer periods after radiation exposure (17% more cancer deaths), especially among those under age 10 at exposure (58% more deaths). Poisson regression methods were used to investigate the magnitude of the radiation-associated risks, the shape of the dose response, and effect modification by gender, age at exposure, and attained age. The risk of all causes of death was positively associated with radiation dose. Importantly, for solid cancers the additive radiation risk (i.e., excess cancer cases per 10(4) person-years per Gy) continues to increase throughout life with a linear dose-response relationship. The sex-averaged excess relative risk per Gy was 0.42 [95% confidence interval (CI): 0.32, 0.53] for all solid cancer at age 70 years after exposure at age 30 based on a linear model. The risk increased by about 29% per decade decrease in age at exposure (95% CI: 17%, 41%). The estimated lowest dose range with a significant ERR for all solid cancer was 0 to 0.20 Gy, and a formal dose-threshold analysis indicated no threshold; i.e., zero dose was the best estimate of the threshold. The risk of cancer mortality increased significantly for most major sites, including stomach, lung, liver, colon, breast, gallbladder, esophagus, bladder and ovary, whereas rectum, pancreas, uterus, prostate and kidney parenchyma did not have significantly increased risks. An increased risk of non-neoplastic diseases including the circulatory, respiratory and digestive systems was observed, but whether these are causal relationships requires further investigation. There was no evidence of a radiation effect for infectious or external causes of death.
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            A record-based case-control study of natural background radiation and the incidence of childhood leukaemia and other cancers in Great Britain during 1980-2006.

            We conducted a large record-based case-control study testing associations between childhood cancer and natural background radiation. Cases (27,447) born and diagnosed in Great Britain during 1980-2006 and matched cancer-free controls (36,793) were from the National Registry of Childhood Tumours. Radiation exposures were estimated for mother's residence at the child's birth from national databases, using the County District mean for gamma rays, and a predictive map based on domestic measurements grouped by geological boundaries for radon. There was 12% excess relative risk (ERR) (95% CI 3, 22; two-sided P=0.01) of childhood leukaemia per millisievert of cumulative red bone marrow dose from gamma radiation; the analogous association for radon was not significant, ERR 3% (95% CI -4, 11; P=0.35). Associations for other childhood cancers were not significant for either exposure. Excess risk was insensitive to adjustment for measures of socio-economic status. The statistically significant leukaemia risk reported in this reasonably powered study (power ~50%) is consistent with high-dose rate predictions. Substantial bias is unlikely, and we cannot identify mechanisms by which confounding might plausibly account for the association, which we regard as likely to be causal. The study supports the extrapolation of high-dose rate risk models to protracted exposures at natural background exposure levels.
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              Risk of cancer incidence before the age of 15 years after exposure to ionising radiation from computed tomography: results from a German cohort study.

              The aim of this cohort study was to assess the risk of developing cancer, specifically leukaemia, tumours of the central nervous system and lymphoma, before the age of 15 years in children previously exposed to computed tomography (CT) in Germany. Data for children with at least one CT between 1980 and 2010 were abstracted from 20 hospitals. Cancer cases occurring between 1980 and 2010 were identified by stochastic linkage with the German Childhood Cancer Registry (GCCR). For all cases and a sample of non-cases, radiology reports were reviewed to assess the underlying medical conditions at time of the CT. Cases were only included if diagnosis occurred at least 2 years after the first CT and no signs of cancer were recorded in the radiology reports. Standardised incidence ratios (SIR) using incidence rates from the general population were estimated. The cohort included information on 71,073 CT examinations in 44,584 children contributing 161,407 person-years at risk with 46 cases initially identified through linkage with the GCCR. Seven cases had to be excluded due to signs possibly suggestive of cancer at the time of first CT. Overall, more cancer cases were observed (O) than expected (E), but this was mainly driven by unexpected and possibly biased results for lymphomas. For leukaemia, the SIR (SIR = O/E) was 1.72 (95 % CI 0.89-3.01, O = 12), and for CNS tumours, the SIR was 1.35 (95 % CI 0.54-2.78, O = 7). Despite careful examination of the medical information, confounding by indication or reverse causation cannot be ruled out completely and may explain parts of the excess. Furthermore, the CT exposure may have been underestimated as only data from the participating clinics were available. This should be taken into account when interpreting risk estimates.
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                Author and article information

                Contributors
                0191 282 1352 , richard.harbron@ncl.ac.uk
                Journal
                Eur J Epidemiol
                Eur. J. Epidemiol
                European Journal of Epidemiology
                Springer Netherlands (Dordrecht )
                0393-2990
                1573-7284
                18 January 2018
                18 January 2018
                2018
                : 33
                : 4
                : 393-401
                Affiliations
                [1 ]ISNI 0000 0001 0462 7212, GRID grid.1006.7, Institute of Health and Society, Sir James Spence Institute, Royal Victoria Infirmary, , Newcastle University, ; Newcastle upon Tyne, NE1 4LP UK
                [2 ]ISNI 0000 0001 0462 7212, GRID grid.1006.7, NIHR Health Protection Research Unit in Chemical and Radiation Threats and Hazards, , Newcastle University, ; Newcastle upon Tyne, NE2 4AA UK
                [3 ]ISNI 0000 0004 0444 2244, GRID grid.420004.2, Regional Medical Physics Department, Freeman Hospital, , Newcastle-upon-Tyne Hospitals NHS Trust, ; Newcastle upon Tyne, NE7 7DN UK
                [4 ]ISNI 0000 0004 0444 2244, GRID grid.420004.2, Paediatric Cardiology, Freeman Hospital, , Newcastle upon Tyne Hospitals NHS Foundation Trust, ; Newcastle upon Tyne, NE7 7DN UK
                [5 ]ISNI 0000 0001 2297 5165, GRID grid.94365.3d, Division of Cancer Epidemiology and Genetics, National Cancer Institute, , National Institutes of Health, ; Bethesda, MD USA
                [6 ]ISNI 0000 0004 5902 9895, GRID grid.424537.3, Radiology Department, , Great Ormond Street Hospital for Children NHS Trust, ; London, UK
                [7 ]ISNI 0000 0004 0467 2410, GRID grid.462072.5, Basque Center for Applied Mathematics, ; Alameda de Mazarredo, 14, 48009 Bilbao, Basque Country Spain
                Author information
                http://orcid.org/0000-0001-6073-2850
                Article
                357
                10.1007/s10654-018-0357-0
                5945801
                29349586
                8eb0bd73-d553-40d7-9553-a7810cfc4489
                © The Author(s) 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 24 July 2017
                : 12 January 2018
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100000274, British Heart Foundation;
                Award ID: PG/15/1/31217
                Award Recipient :
                Funded by: Newcastle Healthcare Charity
                Award ID: N/A
                Award Recipient :
                Categories
                Radiation Epidemiology
                Custom metadata
                © Springer Science+Business Media B.V., part of Springer Nature 2018

                Public health
                cardiac,radiation exposure,dose,transplant,cancer
                Public health
                cardiac, radiation exposure, dose, transplant, cancer

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