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Inflammatory disease and C-reactive protein in relation to therapeutic ionising radiation exposure in the US Radiologic Technologists.

ABSTRACT: Chronic inflammation underlies many autoimmune diseases, including hypothyroidism, hyperthyroidism, and rheumatoid arthritis, also type-2 diabetes and osteoarthritis. Associations have been suggested of high-dose ionising radiation exposure with type-2 diabetes and elevated levels of C-reactive protein, a marker of chronic inflammation. In this analysis we used a proportional hazards model to assess effects of radiotherapy on risks of subsequent inflammatory disease morbidity in 110,368 US radiologic technologists followed from a baseline survey (1983-1989/1994-1998) through 2008. We used a linear model to assess log-transformed C-reactive protein concentration following radiotherapy in 1326 technologists. Relative risk of diabetes increased following radiotherapy (p < 0.001), and there was a borderline significant increasing trend per treatment (p = 0.092). For osteoarthritis there was increased relative risk associated with prior radiotherapy on all questionnaires (p = 0.005), and a significant increasing trend per previous treatment (p = 0.024). No consistent increases were observed for other types of inflammatory disease (hypothyroidism, hyperthyroidism, rheumatoid arthritis) associated with radiotherapy. There was a borderline significant (p = 0.059) increasing trend with dose for C-reactive protein with numbers of prior radiotherapy treatments. Our results suggest that radiotherapy is associated with subsequent increased risk of certain inflammatory conditions, which is reinforced by our finding of elevated levels of C-reactive protein.

SUBMITTER: Little MP

PROVIDER: S-EPMC6426979 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Occupational ionising radiation and risk of basal cell carcinoma in US radiologic technologists (1983-2005).

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| S-EPMC5066420 | biostudies-literature

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Project description:Ionizing radiation-associated breast cancer risk appears to be modified by timing of reproductive events such as age at radiation exposure, parity, age at first live birth, and age at menopause. However, potential breast cancer risk modification of low to moderate radiation dose by polymorphic estrogen metabolism-related gene variants has not been routinely investigated. We assessed breast cancer risk of 12 candidate variants in 12 genes involved in steroid metabolism, catabolism, binding, or receptor functions in a study of 859 cases and 1,083 controls within the US radiologic technologists (USRT) cohort. Using cumulative breast dose estimates from a detailed assessment of occupational and personal diagnostic ionizing radiation exposure, we investigated the joint effects of genotype on the risk of breast cancer. In multivariate analyses, we observed a significantly decreased risk of breast cancer associated with the CYP3A4 M445T minor allele (rs4986910, OR = 0.3; 95% CI 0.1-0.9). We found a borderline increased breast cancer risk with having both minor alleles of CYP1B1 V432L (rs1056836, CC vs. GG, OR = 1.2; 95% CI 0.9-1.6). Assuming a recessive model, the minor allele of CYP1B1 V432L significantly increased the dose-response relationship between personal diagnostic X-ray exposure and breast cancer risk, adjusted for cumulative occupational radiation dose (p (interaction) = 0.03) and had a similar joint effect for cumulative occupational radiation dose adjusted for personal diagnostic X-ray exposure (p (interaction) = 0.06). We found suggestive evidence that common variants in selected estrogen metabolizing genes may modify the association between ionizing radiation exposure and breast cancer risk.

| S-EPMC2860373 | biostudies-literature

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Project description:BackgroundAlthough high-dose ionising radiation is associated with increased breast cancer risks, the association with protracted low-dose-rate exposures remains unclear. The US Radiologic Technologist study provides an opportunity to examine the association between low-to-moderate dose radiation and breast cancer incidence and mortality.MethodsOne thousand nine hundred and twenty-two self-reported first primary cancers were diagnosed during 1983-2005 among 66?915 female technologists, and 586 breast cancer deaths occurred during 1983-2008 among 83?538 female cohort members. Occupational breast dose estimates were based on work histories, historical data, and, after the mid-1970s, individual film badge measurements. Excess relative risks were estimated using Poisson regression with birth cohort stratification and adjustment for menopause, reproductive history, and other risk factors.ResultsHigher doses were associated with increased breast cancer incidence, with an excess relative risk at 100?mGy of 0.07 (95% confidence interval (CI): -0.005 to 0.19). Associations were strongest for technologists born before 1930 (excess relative risk at 100?mGy=0.16; 95% CI: 0.03-0.39) with similar patterns for mortality among technologists born before 1930.ConclusionsOccupational radiation to the breast was positively associated with breast cancer risk. The risk was more pronounced for women born before 1930 who began working before 1950 when mean annual doses (37?mGy) were considerably higher than in later years (1.3?mGy). However, because of the uncertainties and possible systematic errors in the occupational dose estimates before 1960, these findings should be treated with caution.

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Novel breast cancer risk alleles and interaction with ionizing radiation among U.S. radiologic technologists.

Project description:As genome-wide association studies of breast cancer are replicating findings and refinement studies are narrowing the signal location, additional efforts are necessary to elucidate the underlying functional relationships. One approach is to evaluate variation in risk by genotype based on known breast carcinogens, such as ionizing radiation. Given the public health concerns associated with recent increases in medical radiation exposure, this approach may also identify potentially susceptible subpopulations. We examined interaction between 27 newly identified breast cancer risk alleles (identified within the NCI Cancer Genetic Markers of Susceptibility and the Breast Cancer Association Consortium genome-wide association studies) and occupational and medical diagnostic radiation exposure among 859 cases and 1083 controls nested within the United States Radiologic Technologists cohort. We did not find significant variation in the radiation-related breast cancer risk for the variant in RAD51L1 (rs10483813) on 14q24.1 as we had hypothesized. In exploratory analyses, we found that the radiation-associated breast cancer risk varied significantly by linked markers in 5p12 (rs930395, rs10941679, rs2067980 and rs4415084) in the mitochondrial ribosomal protein S30 (MRPS30) gene (P(interaction) = 0.04). Chance, however, may explain these findings, and as such, these results need to be confirmed in other populations with low to moderate levels of radiation exposure. Even though a complete understanding of the way(s) in which these variants may increase breast cancer risk remains elusive, this approach may yield clues for further investigation.

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Nucleotide excision repair polymorphisms may modify ionizing radiation-related breast cancer risk in US radiologic technologists.

Project description:Exposure to ionizing radiation has been consistently associated with increased risk of female breast cancer. Although the majority of DNA damage caused by ionizing radiation is corrected by the base-excision repair pathway, certain types of multiple-base damage can only be repaired through the nucleotide excision repair pathway. In a nested case-control study of breast cancer in US radiologic technologists exposed to low levels of ionizing radiation (858 cases, 1,083 controls), we examined whether risk of breast cancer conferred by radiation was modified by nucleotide excision gene polymorphisms ERCC2 (XPD) rs13181, ERCC4 (XPF) rs1800067 and rs1800124, ERCC5 (XPG) rs1047769 and rs17655; and ERCC6 rs2228526. Of the 6 ERCC variants examined, only ERCC5 rs17655 showed a borderline main effect association with breast cancer risk (OR(GC) = 1.1, OR(CC) = 1.3; p-trend = 0.08), with some indication that individuals carrying the C allele variant were more susceptible to the effects of occupational radiation (EOR/Gy(GG) = 1.0, 95% CI = <0, 6.0; EOR/Gy(GC/CC) = 5.9, 95% CI = 0.9, 14.4; p(het) = 0.10). ERCC2 rs13181, although not associated with breast cancer risk overall, statistically significantly modified the effect of occupational radiation dose on risk of breast cancer (EOR/Gy(AA) = 9.1, 95% CI = 2.1-21.3; EOR/Gy(AC/CC) = 0.6, 95% CI = <0, 4.6; p(het) = 0.01). These results suggest that common variants in nucleotide excision repair genes may modify the association between occupational radiation exposure and breast cancer risk.

| S-EPMC3984912 | biostudies-literature

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