Cancer Risk in People Exposed to CT Scans in Childhood
Cancer Risk in People Exposed to CT Scans in Childhood
The cohort included 10,939,680 people. Based on a one year lag period, 680 211 (6.2%) were transferred into the CT exposed group before their exit from the study ( Table 1 ), and 18% of the exposed group had more than one scan ( Table 2 ). Mean length of follow-up was 9.5 years for the exposed group and 17.3 years for the unexposed group. By 31 December 2007, 3150 individuals in the exposed group and 57,524 individuals in the unexposed group had been diagnosed with a cancer, giving a total of 60,674 people with a cancer. For all types of cancer combined, incidence was 24% greater in the exposed group than in the unexposed group (IRR 1.24 (95% confidence interval 1.20 to 1.29) after stratification for age, sex, and year of birth, P<0.001), and the IRR increased by 0.16 (0.13 to 0.19) with each additional CT scan (P<0.001 for trend; Figure 2. When the calculations were repeated based on lag periods of five and 10 years, cancer incidence remained higher in the exposed group than in the unexposed group, although the proportional increases were smaller compared with those based on the one year lag period (five year lag period: IRR 1.21 (1.16 to 1.26), P<0.001; 10 year lag period: 1.18 (1.11 to 1.24), P<0.001; Table 3 ). For lag periods of five and 10 years, the IRR increased by 0.13 (0.10 to 0.16) and 0.10 (0.06 to 0.15), respectively, for each additional scan (Web Figure A).
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Figure 2.
Incidence rate ratios (IRR) for all types of cancers in exposed versus unexposed individuals based on a one year lag period, by the number of CT scans. The IRR increased by 0.16 (95% confidence interval 0.13 to 0.19) for each additional CT scan, calculated after stratification for age, sex, and year of birth (χ =131.4 and P<0.001 for trend). If unexposed people were excluded, the trend remained significant (χ =5.79 and P=0.02 for trend). The average number of scans among individuals exposed to three or more scans was 3.5. (Web figure A shows corresponding results based on lag periods of five and 10 years).
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Web Figure A.
Incidence rate ratios (IRR), exposed versus unexposed, for cancers of all types and 95% confidence intervals(CI) by number of CT scans, based on 5 and 10 year lag periods.
a) Based on a 5 year lag, the incidence rate increased by 0.13 (95% CI 0.10 to 0.16) for each additional CT scan, calculated after stratification for age, sex, and year of birth (χ for trend: 65.3, 2p <0.0001). If unexposed persons are excluded, the trend is no longer significant (χ for trend: 0.26, 2p = 0.62).
b) Based on a 10 year lag, the incidence rate increased by an average factor of 0.10 (95% CI 0.06 to 0.15) for every additional CT scan calculated after stratification for age, sex, and year of birth (χ for trend: 24.7, p<0.0001). If unexposed persons are excluded, the trend is no longer significant (χ for trend: 0.46, 2p = 0.50). For both 5 and 10 year lags, the average number of scans among individuals exposed to 3+ scans was 3.5.
The IRR for the exposed group versus the unexposed group was increased not only for all cancers combined but also for all solid cancers and for all lymphoid and haematopoietic cancers when these were considered separately ( Table 4 ). Among specific malignancies, brain cancer had the largest IRR, although incidence was also increased significantly for cancers of the digestive organs, melanoma, soft tissue, female genital organs, urinary tract, thyroid, ill defined and unspecified sites, Hodgkin's lymphoma, other lymphoid cancers, leukaemias and myelodysplasias, all leukaemias, myeloid and other leukaemias, and myelodysplasias ( Table 4 ). We saw no separate increase in IRR for breast cancer or lymphoid leukaemia. The estimated total number of excess cancers for the exposed group was 608, with melanoma, soft tissue cancers, brain cancer, thyroid cancer, and all lymphoid and haematopoietic cancer each contributing more than 50 cases ( Table 4 ). EIRs were 9.38 per 100,000 person years for all cancers combined, and more than 1 per 100 000 person years each for melanoma, brain cancer, thyroid cancer, and all lymphoid and haematopoietic cancers. Results by cancer type were consistent when we repeated the analysis using lag periods of five and 10 years ( Web Table A and Web Table B , respectively).
For brain cancer, both the proportional increase in the incidence rate and the absolute excess incidence rate in the exposed group were greatest 1-4 years after first CT exposure, after which they declined (P<0.001 for IRR trend, P=0.03 for EIR trend). Nevertheless, brain cancer incidence was still increased significantly at 15 or more years following first exposure ( Table 5 ). For other solid cancers, there was no significant trend in the proportional increase in incidence rate with time since first exposure (P=0.88 for IRR trend), although the absolute excess incidence rate increased with time since first exposure (P=0.01 for EIR trend). For leukaemias and myelodysplasias and for other lymphoid and haematopoietic cancers, there were no significant trends with time since first exposure in either the proportional increase (IRR) or the absolute increase (EIR) in incidence rate. For all cancers combined, the proportional increase in the incidence rate declined with years since the first CT scan (P=0.009 for IRR trend), but the incidence rate for all cancers combined in the exposed group was still increased at 15 or more years after first exposure (IRR 1.24,95% confidence interval 1.14 to 1.34). We saw no significant trend in EIR for all cancers combined (P=0.43 for trend).
For brain cancer, the IRR for a given time since first exposure was less if the exposure happened in a later calendar period (P<0.001 for trend), but for all solid cancers other than brain cancer and for all cancers combined, the trends in IRR with calendar period of first exposure were not significant (P=0.68 and P=0.18, respectively; Table 6 , Web Table C , Web Figure B and Web Figure C).
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Web Figure B.
Incidence rate ratios, exposed versus unexposed, for selected cancers by years since exposure and calendar period of first exposure, based on a 1 year lag period.
Incidence rate ratios, exposed versus unexposed, calculated after stratification for age, sex, and year of birth.
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Web Figure C.
Absolute excess incidence rates per 100,000 person-years in exposed persons, for selected cancers by years since exposure and calendar period of first exposure, based on a 1 year lag period.
Absolute excess incidence rates compared with rates in unexposed persons, after stratification for age, sex, and year of birth.
For brain cancer and for all cancers combined, IRRs were highest for CT exposures in children younger than 5 years, and decreased with increasing age at first exposure (P=0.001 for trend for brain cancer, P<0.001 for trend for all cancers; Table 7 ). For all solid cancers other than brain cancer, the IRR also tended to decrease with increasing age at first exposure (P=0.06 for trend). Despite these reductions, the IRR remained significantly increased in the oldest group at first exposure, for brain cancers, all cancers combined, and all solid cancers other than brain cancer. For lymphoid and haematopoietic cancers other than leukaemias and myelodysplasias, the IRR also fell with increasing age at first exposure (P=0.04 for trend). For leukaemias and myelodysplasias, however, the IRR tended to increase with age at first exposure (P=0.06 for trend). Nearly half of the exposed group had their first CT scan at ages 15-19 ( Table 2 ). Therefore, despite the IRR reduction with increasing age at first exposure for all cancers combined, over half the excess cancers (338 of 608) occurred among those first exposed at ages 15-19 years.
For brain cancer, leukaemias and myelodysplasias, other lymphoid and haematopoietic cancers, and all cancers combined, neither the IRR nor the EIR differed significantly between the sexes ( Web Table D ). However, for solid cancers other than brain cancer, the IRR was greater in female patients than in male patients (1.23 (95% confidence interval 1.16 to 1.31) v 1.14 (1.07 to 1.22), P=0.07 for difference); the EIR was also significantly greater in female patients than for male patients (7.59 (5.35 to 9.82) v 3.57 (1.76 to 5.37), P=0.006 for difference). Socioeconomic status was only weakly related to CT scan exposure ( Table 1 ), and the effect of exposure did not differ significantly according to socioeconomic status ( Web Table E ). Information was not available for potential confounding factors such as alcohol, smoking, sun exposure, or for Down's syndrome or other markers of cancer susceptibility. However, because the CT related increase in cancer risk varied very little by socioeconomic status, it is unlikely that our results were substantially biased by confounding factors such as these.
For all cancers combined, the IRR in the exposed group versus the unexposed group was significantly increased (P<0.05) for very anatomical site of CT scan considered (Figure 3). The IRRs differed according to the site of the CT scan (P<0.001 for heterogeneity), with larger increases after CT scans of the chest (1.62) and abdomen or pelvis (1.61), and smaller increases after CT scans of the facial bones (1.14) and spine or neck (1.13). For some CT sites, the IRR also varied between different types of cancer (P<0.001 for heterogeneity after scans of head or brain; P=0.02 after scans of abdomen or pelvis). After CT scans of the brain, the largest IRR was for brain cancer (2.44, 95% confidence interval 2.12 to 2.81), although there were also significant (P<0.05) increases for melanoma, soft tissue cancers, thyroid cancer, and other solid cancers. After scans of the abdomen or pelvis, the largest IRR was for leukaemias and myelodysplasias (3.24, 2.17 to 4.84); there were also significant increases for soft tissue cancer, brain cancer, and all other solid cancers apart from melanoma and thyroid cancer. Web Figure D shows corresponding results based on a five year lag period.
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Figure 3.
Incidence rate ratios (IRR) for exposed versus unexposed by site of CT scan and type of cancer, based on a one year lag period. IRRs were calculated after stratification for age, sex, and year of birth. Heterogeneity between cancer types, by site of CT scan exposure: all sites, χ=23.58 (6 df), P=0.001; brain, χ=104.1 (6 df), P<0.001; abdomen or pelvis, χ=15.7 (6 df), P=0.02. Heterogeneity between sites of CT scan exposure, by cancer type: all cancers, χ=111.1 (6 df), P<0.001 brain, Ă·2=13.9 (6 df), P=0.03; leukaemia, χ=24.81 6 df), P<0.001.
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Web Figure D.
Incidence rate ratios (IRR), exposed versus unexposed, and 95% confidence intervals (CI) by site of CT scan and type of cancer, based on a 5 year lag period.
Incidence rate ratios versus unexposed calculated after stratification for age, sex, and year of birth. Heterogeneity between cancer types — all sites of CT scan exposure: χ = 33.5 on 6 df, p<0.001; brain scans: χ = 36.5 on 6 df, p<0.001. Heterogeneity between sites of CT scan exposure — all cancers: χ = 9.04 on 6 df, p=0.156; brain cancer: χ = 12.48 on 6 df, p=0.052; leukaemias: χ = 7.24 on 5 df, p=0.211.
Almost 60% of CT scans were of the brain ( Table 2 ), and some low grade cancers in the brain may have given rise to symptoms that were investigated several years before they were finally diagnosed (that is, the brain cancer may have caused the scan, rather than vice versa). To explore the extent to which our results might have been affected by such reverse causation, we repeated our main analyses excluding any brain cancers that occurred after a CT scan of the brain. For all cancers other than brain cancers following a brain CT, the increase in IRR with increasing number of CT scans was maintained (Web Figure E). The IRR for brain cancers after a scan to a site other than the brain remained raised (1.51 (95% confidence interval 1.19 to 1.91), Table 4 ) as did the IRRs for all solid cancers (1.20, 1.15 to 1.25) and for all cancers (1.20,1.15 to 1.24).The IRR for the remaining brain cancers tended to decrease with increasing time since first exposure, although the trend did not reach significance (P=0.06 for trend, Table 5 ). The trend with time since first exposure in the IRR for all cancers (except brain cancer after a brain CT) was also not significant (P=0.30 for trend, Table 5 ). In any given period after exposure, there was no significant association between the IRR for all solid cancers (except brain cancer after a brain CT) and the calendar year of first exposure (P=0.68 for trend, Web Table C ). The reduction in IRR for all solid cancers (except brain cancer after a brain CT scan) with increasing age at exposure was highly significant (P=0.01 for trend, Table 7 ), but there was no significant trend in the EIR with increasing age at exposure (P=0.21 for trend).
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Web Figure E.
Incidence rate ratios (IRR), exposed versus unexposed, for all cancers except brain cancer after brain CT and 95% confidence intervals (CI) based on a 1 year lag period, by number of CT scans.
The incidence rate ratio increased by 0.14 (95% CI 0.11 to 0.17) for each additional CT scan, calculated after stratification for age, sex, and year of birth (χ for trend: 94.7 , p<0.0001). If unexposed persons are excluded the trend remains significant (χ for trend: 7.90 p =0.005). The average number of scans among individuals exposed to 3+ scans was 3.5.
Based on a one year lag period, the collective effective dose from all CT scans combined was about 3900 Sv, and the average effective dose to all organs of the body was about 4.5 mSv per scan. On the assumption that all the excess cancers, apart from brain cancers after CT scans of the brain, are attributable to CT scans, this suggests that each sievert of effective dose caused 0.125 cancers by 31 December 2007 ( Table 8 ) in an average follow-up period of 9.5 years. So far, one in every 1800 CT scans has been followed by an excess cancer, with an excess rate ratio per mSv of 0.035 (95% confidence interval 0.026 to 0.042). A similar calculation considering only brain cancers after a brain CT suggests a collective organ dose to the brain of 19,800 Gy from an average brain dose of 40 mGy per brain scan. If CT scans had caused all the excess of brain cancer in this group, each Gy to the brain would have led to 0.006 brain cancers by the end of available follow-up (31 December 2007), one in 4000 brain scans would have led to a brain cancer, and the excess rate ratio of brain cancers per mGy to the brain would be 0.029 (95% confidence interval 0.023 to 0.037). The estimated collective dose to red bone marrow, based on a one year lag period, was 4000 Gy, and the average estimated red bone marrow dose was 4.6 mGy per scan. This suggests that each gray of radiation to the red bone marrow has led to 0.012 excess leukaemias or myelodysplasias to date, and that the excess rate ratio for leukaemias and myelodysplasias per mGy to the red bone marrow is 0.039 (95% confidence interval 0.014 to 0.070). When these calculations were repeated for lag periods of five and 10 years, the collective doses were considerably lower, and the excess rate ratio per mSv was slightly reduced for all cancers except brain cancer following a brain scan, more reduced for brain cancer following a brain scan, and substantially reduced for leukaemias and myelodysplasias at a 10 year lag ( Table 8 ).
Results
Study Population and Overall Risks
The cohort included 10,939,680 people. Based on a one year lag period, 680 211 (6.2%) were transferred into the CT exposed group before their exit from the study ( Table 1 ), and 18% of the exposed group had more than one scan ( Table 2 ). Mean length of follow-up was 9.5 years for the exposed group and 17.3 years for the unexposed group. By 31 December 2007, 3150 individuals in the exposed group and 57,524 individuals in the unexposed group had been diagnosed with a cancer, giving a total of 60,674 people with a cancer. For all types of cancer combined, incidence was 24% greater in the exposed group than in the unexposed group (IRR 1.24 (95% confidence interval 1.20 to 1.29) after stratification for age, sex, and year of birth, P<0.001), and the IRR increased by 0.16 (0.13 to 0.19) with each additional CT scan (P<0.001 for trend; Figure 2. When the calculations were repeated based on lag periods of five and 10 years, cancer incidence remained higher in the exposed group than in the unexposed group, although the proportional increases were smaller compared with those based on the one year lag period (five year lag period: IRR 1.21 (1.16 to 1.26), P<0.001; 10 year lag period: 1.18 (1.11 to 1.24), P<0.001; Table 3 ). For lag periods of five and 10 years, the IRR increased by 0.13 (0.10 to 0.16) and 0.10 (0.06 to 0.15), respectively, for each additional scan (Web Figure A).
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Figure 2.
Incidence rate ratios (IRR) for all types of cancers in exposed versus unexposed individuals based on a one year lag period, by the number of CT scans. The IRR increased by 0.16 (95% confidence interval 0.13 to 0.19) for each additional CT scan, calculated after stratification for age, sex, and year of birth (χ =131.4 and P<0.001 for trend). If unexposed people were excluded, the trend remained significant (χ =5.79 and P=0.02 for trend). The average number of scans among individuals exposed to three or more scans was 3.5. (Web figure A shows corresponding results based on lag periods of five and 10 years).
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Web Figure A.
Incidence rate ratios (IRR), exposed versus unexposed, for cancers of all types and 95% confidence intervals(CI) by number of CT scans, based on 5 and 10 year lag periods.
a) Based on a 5 year lag, the incidence rate increased by 0.13 (95% CI 0.10 to 0.16) for each additional CT scan, calculated after stratification for age, sex, and year of birth (χ for trend: 65.3, 2p <0.0001). If unexposed persons are excluded, the trend is no longer significant (χ for trend: 0.26, 2p = 0.62).
b) Based on a 10 year lag, the incidence rate increased by an average factor of 0.10 (95% CI 0.06 to 0.15) for every additional CT scan calculated after stratification for age, sex, and year of birth (χ for trend: 24.7, p<0.0001). If unexposed persons are excluded, the trend is no longer significant (χ for trend: 0.46, 2p = 0.50). For both 5 and 10 year lags, the average number of scans among individuals exposed to 3+ scans was 3.5.
Risks for Specific Cancers
The IRR for the exposed group versus the unexposed group was increased not only for all cancers combined but also for all solid cancers and for all lymphoid and haematopoietic cancers when these were considered separately ( Table 4 ). Among specific malignancies, brain cancer had the largest IRR, although incidence was also increased significantly for cancers of the digestive organs, melanoma, soft tissue, female genital organs, urinary tract, thyroid, ill defined and unspecified sites, Hodgkin's lymphoma, other lymphoid cancers, leukaemias and myelodysplasias, all leukaemias, myeloid and other leukaemias, and myelodysplasias ( Table 4 ). We saw no separate increase in IRR for breast cancer or lymphoid leukaemia. The estimated total number of excess cancers for the exposed group was 608, with melanoma, soft tissue cancers, brain cancer, thyroid cancer, and all lymphoid and haematopoietic cancer each contributing more than 50 cases ( Table 4 ). EIRs were 9.38 per 100,000 person years for all cancers combined, and more than 1 per 100 000 person years each for melanoma, brain cancer, thyroid cancer, and all lymphoid and haematopoietic cancers. Results by cancer type were consistent when we repeated the analysis using lag periods of five and 10 years ( Web Table A and Web Table B , respectively).
Effects of Time Since Exposure, Year of Exposure, Age at Exposure, Sex, Socioeconomic Status, and Other Potential Confounding Factors
For brain cancer, both the proportional increase in the incidence rate and the absolute excess incidence rate in the exposed group were greatest 1-4 years after first CT exposure, after which they declined (P<0.001 for IRR trend, P=0.03 for EIR trend). Nevertheless, brain cancer incidence was still increased significantly at 15 or more years following first exposure ( Table 5 ). For other solid cancers, there was no significant trend in the proportional increase in incidence rate with time since first exposure (P=0.88 for IRR trend), although the absolute excess incidence rate increased with time since first exposure (P=0.01 for EIR trend). For leukaemias and myelodysplasias and for other lymphoid and haematopoietic cancers, there were no significant trends with time since first exposure in either the proportional increase (IRR) or the absolute increase (EIR) in incidence rate. For all cancers combined, the proportional increase in the incidence rate declined with years since the first CT scan (P=0.009 for IRR trend), but the incidence rate for all cancers combined in the exposed group was still increased at 15 or more years after first exposure (IRR 1.24,95% confidence interval 1.14 to 1.34). We saw no significant trend in EIR for all cancers combined (P=0.43 for trend).
For brain cancer, the IRR for a given time since first exposure was less if the exposure happened in a later calendar period (P<0.001 for trend), but for all solid cancers other than brain cancer and for all cancers combined, the trends in IRR with calendar period of first exposure were not significant (P=0.68 and P=0.18, respectively; Table 6 , Web Table C , Web Figure B and Web Figure C).
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Web Figure B.
Incidence rate ratios, exposed versus unexposed, for selected cancers by years since exposure and calendar period of first exposure, based on a 1 year lag period.
Incidence rate ratios, exposed versus unexposed, calculated after stratification for age, sex, and year of birth.
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Web Figure C.
Absolute excess incidence rates per 100,000 person-years in exposed persons, for selected cancers by years since exposure and calendar period of first exposure, based on a 1 year lag period.
Absolute excess incidence rates compared with rates in unexposed persons, after stratification for age, sex, and year of birth.
For brain cancer and for all cancers combined, IRRs were highest for CT exposures in children younger than 5 years, and decreased with increasing age at first exposure (P=0.001 for trend for brain cancer, P<0.001 for trend for all cancers; Table 7 ). For all solid cancers other than brain cancer, the IRR also tended to decrease with increasing age at first exposure (P=0.06 for trend). Despite these reductions, the IRR remained significantly increased in the oldest group at first exposure, for brain cancers, all cancers combined, and all solid cancers other than brain cancer. For lymphoid and haematopoietic cancers other than leukaemias and myelodysplasias, the IRR also fell with increasing age at first exposure (P=0.04 for trend). For leukaemias and myelodysplasias, however, the IRR tended to increase with age at first exposure (P=0.06 for trend). Nearly half of the exposed group had their first CT scan at ages 15-19 ( Table 2 ). Therefore, despite the IRR reduction with increasing age at first exposure for all cancers combined, over half the excess cancers (338 of 608) occurred among those first exposed at ages 15-19 years.
For brain cancer, leukaemias and myelodysplasias, other lymphoid and haematopoietic cancers, and all cancers combined, neither the IRR nor the EIR differed significantly between the sexes ( Web Table D ). However, for solid cancers other than brain cancer, the IRR was greater in female patients than in male patients (1.23 (95% confidence interval 1.16 to 1.31) v 1.14 (1.07 to 1.22), P=0.07 for difference); the EIR was also significantly greater in female patients than for male patients (7.59 (5.35 to 9.82) v 3.57 (1.76 to 5.37), P=0.006 for difference). Socioeconomic status was only weakly related to CT scan exposure ( Table 1 ), and the effect of exposure did not differ significantly according to socioeconomic status ( Web Table E ). Information was not available for potential confounding factors such as alcohol, smoking, sun exposure, or for Down's syndrome or other markers of cancer susceptibility. However, because the CT related increase in cancer risk varied very little by socioeconomic status, it is unlikely that our results were substantially biased by confounding factors such as these.
Cancer Risk by Site of CT Scan
For all cancers combined, the IRR in the exposed group versus the unexposed group was significantly increased (P<0.05) for very anatomical site of CT scan considered (Figure 3). The IRRs differed according to the site of the CT scan (P<0.001 for heterogeneity), with larger increases after CT scans of the chest (1.62) and abdomen or pelvis (1.61), and smaller increases after CT scans of the facial bones (1.14) and spine or neck (1.13). For some CT sites, the IRR also varied between different types of cancer (P<0.001 for heterogeneity after scans of head or brain; P=0.02 after scans of abdomen or pelvis). After CT scans of the brain, the largest IRR was for brain cancer (2.44, 95% confidence interval 2.12 to 2.81), although there were also significant (P<0.05) increases for melanoma, soft tissue cancers, thyroid cancer, and other solid cancers. After scans of the abdomen or pelvis, the largest IRR was for leukaemias and myelodysplasias (3.24, 2.17 to 4.84); there were also significant increases for soft tissue cancer, brain cancer, and all other solid cancers apart from melanoma and thyroid cancer. Web Figure D shows corresponding results based on a five year lag period.
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Figure 3.
Incidence rate ratios (IRR) for exposed versus unexposed by site of CT scan and type of cancer, based on a one year lag period. IRRs were calculated after stratification for age, sex, and year of birth. Heterogeneity between cancer types, by site of CT scan exposure: all sites, χ=23.58 (6 df), P=0.001; brain, χ=104.1 (6 df), P<0.001; abdomen or pelvis, χ=15.7 (6 df), P=0.02. Heterogeneity between sites of CT scan exposure, by cancer type: all cancers, χ=111.1 (6 df), P<0.001 brain, Ă·2=13.9 (6 df), P=0.03; leukaemia, χ=24.81 6 df), P<0.001.
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Web Figure D.
Incidence rate ratios (IRR), exposed versus unexposed, and 95% confidence intervals (CI) by site of CT scan and type of cancer, based on a 5 year lag period.
Incidence rate ratios versus unexposed calculated after stratification for age, sex, and year of birth. Heterogeneity between cancer types — all sites of CT scan exposure: χ = 33.5 on 6 df, p<0.001; brain scans: χ = 36.5 on 6 df, p<0.001. Heterogeneity between sites of CT scan exposure — all cancers: χ = 9.04 on 6 df, p=0.156; brain cancer: χ = 12.48 on 6 df, p=0.052; leukaemias: χ = 7.24 on 5 df, p=0.211.
Risks After Exclusion of Brain Cancers After a CT Scan of the Brain
Almost 60% of CT scans were of the brain ( Table 2 ), and some low grade cancers in the brain may have given rise to symptoms that were investigated several years before they were finally diagnosed (that is, the brain cancer may have caused the scan, rather than vice versa). To explore the extent to which our results might have been affected by such reverse causation, we repeated our main analyses excluding any brain cancers that occurred after a CT scan of the brain. For all cancers other than brain cancers following a brain CT, the increase in IRR with increasing number of CT scans was maintained (Web Figure E). The IRR for brain cancers after a scan to a site other than the brain remained raised (1.51 (95% confidence interval 1.19 to 1.91), Table 4 ) as did the IRRs for all solid cancers (1.20, 1.15 to 1.25) and for all cancers (1.20,1.15 to 1.24).The IRR for the remaining brain cancers tended to decrease with increasing time since first exposure, although the trend did not reach significance (P=0.06 for trend, Table 5 ). The trend with time since first exposure in the IRR for all cancers (except brain cancer after a brain CT) was also not significant (P=0.30 for trend, Table 5 ). In any given period after exposure, there was no significant association between the IRR for all solid cancers (except brain cancer after a brain CT) and the calendar year of first exposure (P=0.68 for trend, Web Table C ). The reduction in IRR for all solid cancers (except brain cancer after a brain CT scan) with increasing age at exposure was highly significant (P=0.01 for trend, Table 7 ), but there was no significant trend in the EIR with increasing age at exposure (P=0.21 for trend).
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Web Figure E.
Incidence rate ratios (IRR), exposed versus unexposed, for all cancers except brain cancer after brain CT and 95% confidence intervals (CI) based on a 1 year lag period, by number of CT scans.
The incidence rate ratio increased by 0.14 (95% CI 0.11 to 0.17) for each additional CT scan, calculated after stratification for age, sex, and year of birth (χ for trend: 94.7 , p<0.0001). If unexposed persons are excluded the trend remains significant (χ for trend: 7.90 p =0.005). The average number of scans among individuals exposed to 3+ scans was 3.5.
Approximate Risks to Date Per Unit Dose
Based on a one year lag period, the collective effective dose from all CT scans combined was about 3900 Sv, and the average effective dose to all organs of the body was about 4.5 mSv per scan. On the assumption that all the excess cancers, apart from brain cancers after CT scans of the brain, are attributable to CT scans, this suggests that each sievert of effective dose caused 0.125 cancers by 31 December 2007 ( Table 8 ) in an average follow-up period of 9.5 years. So far, one in every 1800 CT scans has been followed by an excess cancer, with an excess rate ratio per mSv of 0.035 (95% confidence interval 0.026 to 0.042). A similar calculation considering only brain cancers after a brain CT suggests a collective organ dose to the brain of 19,800 Gy from an average brain dose of 40 mGy per brain scan. If CT scans had caused all the excess of brain cancer in this group, each Gy to the brain would have led to 0.006 brain cancers by the end of available follow-up (31 December 2007), one in 4000 brain scans would have led to a brain cancer, and the excess rate ratio of brain cancers per mGy to the brain would be 0.029 (95% confidence interval 0.023 to 0.037). The estimated collective dose to red bone marrow, based on a one year lag period, was 4000 Gy, and the average estimated red bone marrow dose was 4.6 mGy per scan. This suggests that each gray of radiation to the red bone marrow has led to 0.012 excess leukaemias or myelodysplasias to date, and that the excess rate ratio for leukaemias and myelodysplasias per mGy to the red bone marrow is 0.039 (95% confidence interval 0.014 to 0.070). When these calculations were repeated for lag periods of five and 10 years, the collective doses were considerably lower, and the excess rate ratio per mSv was slightly reduced for all cancers except brain cancer following a brain scan, more reduced for brain cancer following a brain scan, and substantially reduced for leukaemias and myelodysplasias at a 10 year lag ( Table 8 ).
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