Breast cancer risk and protracted low-to-moderate dose occupational radiation exposure in the US Radiologic Technologists Cohort, 1983-2008.

BACKGROUND: Although 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. METHODS: One 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. RESULTS: Higher 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. CONCLUSIONS: Occupational 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.

Childhood cancer in the offspring born in 1921-1984 to US radiologic technologists.

We examined the risk of childhood cancer (<20 years) among 105 950 offspring born in 1921-1984 to US radiologic technologist (USRT) cohort members. Parental occupational in utero and preconception ionising radiation (IR) testis or ovary doses were estimated from work history data, badge dose data, and literature doses (the latter doses before 1960). Female and male RTs reported a total of 111 and 34 haematopoietic malignancies and 115 and 34 solid tumours, respectively, in their offspring. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression. Leukaemia (n=63) and solid tumours (n=115) in offspring were not associated with maternal in utero or preconception radiation exposure. Risks for lymphoma (n=44) in those with estimated doses of <0.2, 0.2-1.0, and >1.0 mGy vs no exposure were non-significantly elevated with HRs of 2.3, 1.8, and 2.7. Paternal preconception exposure to estimated cumulative doses above the 95th percentile (82 mGy, n=6 cases) was associated with a non-significant risk of childhood cancer of 1.8 (95% CI 0.7-4.6). In conclusion, we found no convincing evidence of an increased risk of childhood cancer in the offspring of RTs in association with parental occupational radiation exposure.

Incidence of haematopoietic malignancies in US radiologic technologists.

BACKGROUND: There are limited data on risks of haematopoietic malignancies associated with protracted low-to-moderate dose radiation. AIMS: To contribute the first incidence risk estimates for haematopoietic malignancies in relation to work history, procedures, practices, and protective measures in a large population of mostly female medical radiation workers. METHODS: The investigators followed up 71,894 (77.9% female) US radiologic technologists, first certified during 1926-80, from completion of a baseline questionnaire (1983-89) to return of a second questionnaire (1994-98), diagnosis of a first cancer, death, or 31 August 1998 (731,306 person-years), whichever occurred first. Cox proportional hazards regression was used to compute risks. RESULTS: Relative risks (RR) for leukaemias other than chronic lymphocytic leukaemia (non-CLL, 41 cases) were increased among technologists working five or more years before 1950 (RR = 6.6, 95% CI 1.0 to 41.9, based on seven cases) or holding patients 50 or more times for x ray examination (RR = 2.6, 95% CI 1.3 to 5.4). Risks of non-CLL leukaemias were not significantly related to the number of years subjects worked in more recent periods, the year or age first worked, the total years worked, specific procedures or equipment used, or personal radiotherapy. Working as a radiologic technologist was not significantly linked with risk of multiple myeloma (28 cases), non-Hodgkin's lymphoma (118 cases), Hodgkin's lymphoma (31 cases), or chronic lymphocytic leukaemia (23 cases). CONCLUSION: Similar to results for single acute dose and fractionated high dose radiation exposures, there was increased risk for non-CLL leukaemias decades after initial protracted radiation exposure that likely cumulated to low-to-moderate doses.

A single nucleotide polymorphism in the 5' untranslated region of RAD51 and risk of cancer among BRCA1/2 mutation carriers.

RAD51 colocalizes with both BRCA1 and BRCA2, and genetic variants in RAD51 would be candidate BRCA1/2 modifiers. We searched for RAD51 polymorphisms by sequencing 20 individuals. We compared the polymorphism allele frequencies between female BRCA1/2 mutation carriers with and without breast or ovarian cancer and between population-based ovarian cancer cases with BRCA1/2 mutations to cases and controls without mutations. We discovered two single nucleotide polymorphisms (SNPs) at positions 135 g-->c and 172 g-->t of the 5' untranslated region. In an initial group of BRCA1/2 mutation carriers, 14 (21%) of 67 breast cancer cases carried a "c" allele at RAD51:135 g-->c, whereas 8 (7%) of 119 women without breast cancer carried this allele. In a second set of 466 mutation carriers from three centers, the association of RAD51:135 g-->c with breast cancer risk was not confirmed. Analyses restricted to the 216 BRCA2 mutation carriers, however, showed a statistically significant association of the 135 "c" allele with the risk of breast cancer (adjusted odds ratio, 3.2; 95% confidence limit, 1.4-40). BRCA1/2 mutation carriers with ovarian cancer were only about one half as likely to carry the RAD51:135 g-->c SNP. Analysis of the RAD51:135 g-->c SNP in 738 subjects from an Israeli ovarian cancer case-control study was consistent with a lower risk of ovarian cancer among BRCA1/2 mutation carriers with the "c" allele. We have identified a RAD51 5' untranslated region SNP that may be associated with an increased risk of breast cancer and a lower risk of ovarian cancer among BRCA2 mutation carriers. The biochemical basis of this risk modifier is currently unknown.

Comparability of national death index plus and standard procedures for determining causes of death in epidemiologic studies.

PURPOSE: To determine whether causes of death obtained through National Death Index (NDI) Plus are comparable to those obtained by requesting death certificates from state vital statistics offices and having deaths coded by contractor nosologists. METHODS: The authors compared underlying cause of death codes obtained from NDI Plus with those assigned by contractor nosologists for a sample of 250 known decedents. RESULTS: The underlying cause of death codes differed for 18 (7%) of 249 successful matches. Independent coding by an expert National Center for Health Statistics (NCHS) nosologist trainer revealed that seven of these had an NDI Plus code that matched the code provided by the NCHS nosologist and a contractor nosologist code that did not match the NCHS nosologist code, seven had a contractor nosologist code that matched the NCHS nosologist code and an NDI Plus code that did not match the NCHS nosologist code, and four had both an NDI Plus and a contractor nosologist code that did not match the NCHS nosologist code. The level of disagreement with the NCHS nosologist and the organ systems involved were similar for NDI Plus and the contractor nosologist. CONCLUSIONS: The authors report that NDI Plus provides comparable information within a substantially shorter time period for most states and, for known decedents, at about half the cost of standard procedures.

Employment practices and breast cancer among radiologic technologists.

A case-control study of breast cancer and employment practices among female radiologic technologists was conducted. The cohort from which cases and controls were derived included over 105,000 female medical radiation workers certified by the American Registry of Radiologic Technologists during 1926-1980. Breast cancer cases (n = 528) were individually matched to an average of five control subjects (n = 2628) based on year of birth, year of certification, and length of follow-up. Procedures most commonly performed by controls included fluoroscopy (93%), portable radiographs (92%), routine radiographs (92%), multifilm procedures (87%), dental x-rays (46%), radium therapy (31%), orthovoltage (23%), and cobalt-60 (21%). Breast cancer was not significantly increased with occupational experience with any of these procedures. Furthermore, risk was not related to number of years worked with a particular procedure. This study is reassuring in indicating that medical radiation workers are not at substantial risk for developing radiation-induced breast cancer. However, because only surrogate measures of radiation exposure were available, possibility of a small risk cannot be discounted. Ongoing follow-up of this cohort for incident cancers will incorporate detailed exposure assessment schemes, providing additional information on effects of long-term low-dose radiation through occupation.

Breast cancer mortality after diagnostic radiography: findings from the U.S. Scoliosis Cohort Study.

STUDY DESIGN: A retrospective cohort study was conducted in 5573 female patients with scoliosis who were referred for treatment at 14 orthopedic medical centers in the United States. Patients were less than 20 years of age at diagnosis which occurred between 1912 and 1965. OBJECTIVES: To evaluate patterns in breast cancer mortality among women with scoliosis, with special emphasis on risk associated with diagnostic radiograph exposures. SUMMARY OF BACKGROUND DATA: A pilot study of 1030 women with scoliosis revealed a nearly twofold statistically significant increased risk for incident breast cancer. Although based on only 11 cases, findings were consistent with radiation as a causative factor. METHODS: Medical records were reviewed for information on personal characteristics and scoliosis history. Diagnostic radiograph exposures were tabulated based on review of radiographs, radiology reports in the medical records, radiograph jackets, and radiology log books. Radiation doses were estimated for individual examinations. The mortality rate of the cohort through January 1, 1997, was determined by using state and national vital statistics records and was compared with that of women in the general U. S. population. RESULTS: Nearly 138,000 radiographic examinations were recorded. The average number of examinations per patient was 24.7 (range, 0-618); mean estimated cumulative radiation dose to the breast was 10.8 cGy (range, 0-170). After excluding patients with missing information, 5466 patients were included in breast cancer mortality analyses. Their mean age at diagnosis was 10.6 years and average length of follow-up was 40.1 years. There were 77 breast cancer deaths observed compared with the 45.6 deaths expected on the basis of U.S. mortality rates (standardized mortality ratio [SMR] = 1.69; 95% confidence interval [CI] = 1.3-2.1). Risk increased significantly with increasing number of radiograph exposures and with cumulative radiation dose. The unadjusted excess relative risk per Gy was 5.4 (95% CI = 1.2-14.1); when analyses were restricted to patients who had undergone at least one radiographic examination, the risk estimate was 2.7 (95% CI = -0. 2-9.3). CONCLUSIONS: These data suggest that exposure to multiple diagnostic radiographic examinations during childhood and adolescence may increase the risk of breast cancer among women with scoliosis; however, potential confounding between radiation dose and severity of disease and thus with reproductive history may explain some of the increased risk observed.

Body mass index and all-cause mortality in a nationwide US cohort.

OBJECTIVE: To investigate whether the nature of the relationship between body mass index (BMI (kg/m2)) and all-cause mortality is direct, J- or U-shaped, and whether this relationship changes as people age. DESIGN: Prospective nationwide cohort study of US radiologic technologists (USRT). SUBJECTS: Sixty-four thousand seven hundred and thirty-three female and 19 011 male certified radiation technologists. METHODS: We prospectively followed participants from the USRT study who completed a mail survey in 1983-1989 through 2000. During an average of 14.7 years of follow-up or 1.23 million person-years, 2278 women and 1495 men died. Using Cox's proportional-hazards regression analyses, we analyzed the relationship between BMI and all-cause mortality by gender and by age group (<55 years; > or = 55 years). We also examined risk in never-smokers after the first 5 years of follow-up to limit bias owing to the confounding effects of smoking and illness-related weight loss on BMI and mortality. RESULTS: Risks were generally J-shaped for both genders and age groups. When we excluded smokers and the first 5 year of follow-up, risks were substantially reduced in those with low BMIs. In never-smoking women under the age of 55 years (excluding the initial 5-year follow-up period), risk rose as BMI increased above 21.0 kg/m2, whereas in older women, risk increased beginning at a higher BMI (> or = 25.0 kg/m2). Among younger men who never smoked (excluding the initial 5-year follow-up period), risk began to rise above a BMI of 23.0 kg/m2, whereas in older men, risk did not begin to increase until exceeding a BMI of 30.0 kg/m2. CONCLUSIONS: In younger/middle-aged, but not older, women and men, mortality risks appear directly related to BMI. The more complicated relationship between BMI and mortality in older subjects suggests the importance of assessing whether other markers of body composition better explain mortality risk in older adults.

Breast cancer among radiologic technologists.

OBJECTIVE: To evaluate the risk of breast cancer among women occupationally exposed to ionizing radiation. DESIGN: Case-control study. PARTICIPANTS: A health survey of 105,385 women radiologic technologists certified by the American Registry of Radiologic Technologists since 1926. Among 79,016 respondents, 600 breast cancer cases were identified. Each of 528 eligible subjects with breast cancer was matched to five control subjects based on age, year of certification, and follow-up time. MAIN OUTCOME MEASURES: Relative risk (RR) estimated as the relative odds ratio for breast cancer over categories of years worked as a radiologic technologist and according to personal and occupational exposure characteristics. RESULTS: Study subjects had been certified for a mean of 29 years; 63.8% of cases and 62.6% of controls worked as radiologic technologists for 10 years or more. Significant increased risks for breast cancer were associated with early age at menarche (for < 11 years of age: RR = 1.79; 95% confidence interval [CI], 1.09 to 2.94), nulliparity (RR = 1.36; 95% CI, 1.04 to 1.78), first-degree relative with history of breast cancer (RR = 2.07; 95% CI, 1.56 to 2.74), prior breast biopsy (RR = 1.53; 95% CI, 1.17 to 2.00), alcohol consumption (for > 14 alcoholic drinks per week: RR = 2.12; 95% CI, 1.06 to 4.27), thyroid cancer (RR = 5.36; 95% CI, 1.64 to 17.5), hyperthyroidism (RR = 1.66; 95% CI, 1.02 to 2.71), and residence in the northeastern United States (RR = 1.66; 95% CI, 1.19 to 2.30). Jobs involving radiotherapy, radioisotopes, or fluoroscopic equipment, however, were not linked to breast cancer risk, nor were personal exposures to fluoroscopy or multifilm procedures. Use of birth control pills, postmenopausal estrogens, or permanent hair dyes also were not risk factors. Based on dosimetry records for 35% of study subjects, cumulative exposures appeared low. Among women who worked more than 20 years, the RR for breast cancer was 1.13 (95% CI, 0.79 to 1.64). CONCLUSIONS: More than 50% of the reported breast cancers could be explained by established risk factors. Employment as a radiologic technologist, however, was not found to increase the risk of breast cancer. The contribution of prolonged exposure to relatively low doses of ionizing radiation to breast cancer risk was too small to be detectable at this time.

A health survey of radiologic technologists.

A health survey of more than 143,000 radiologic technologists is described. The population was identified from the 1982 computerized files of the American Registry of Radiologic Technologists, which was established in 1926. Inactive members were traced to obtain current addresses or death notifications. More than 6000 technologists were reported to have died. For all registrants who were alive when located, a detailed 16-page questionnaire was sent, covering occupational histories, medical conditions, and other personal and lifestyle characteristics. Nonrespondents were contacted by telephone to complete an abbreviated questionnaire. More than 104,000 responses were obtained. The overall response rate was 79%. Most technologists were female (76%), white (93%), and employed for an average of 12 years; 37% attended college, and approximately 50% never smoked cigarettes. Radiation exposure information was sought from employer records and commercial dosimetry companies. Technologists employed for the longest times had the highest estimated cumulative exposures, with approximately 9% with exposures greater than 5 cGy. There was a high correlation between cumulative occupational exposure and personal exposure to medical radiographs, related, in part, to the association of both factors with attained age. It is interesting that 10% of all technologists allowed others to practice taking radiographs on them during their training. Nearly 4% of the respondents reported having some type of cancer, mainly of the skin (1517), breast (665), and cervix (726). Prospective surveys will monitor cancer mortality rates through use of the National Death Index and cancer incidence through periodic mailings of questionnaires. This is the only occupational study of radiation employees who are primarily women and should provide new information on the possible risks associated with relatively low levels of exposure.

Mortality among United States radiologic technologists, 1926-90.

The possible mortality risk from low level chronic exposures to ionizing radiation was evaluated among 143,517 United States radiologic technologists certified by the American Registry of Radiologic Technologists between 1926-80. This is one of the few occupational studies of primarily women (73 percent) exposed to radiation during their employment. More than 2.8 million person-years of follow-up were accrued through 1990, and 7,345 deaths were identified. A strong healthy-worker effect was observed (standardized mortality ratios [SMR] for all causes and all cancers were 0.69 and 0.79, respectively). Lung cancer (429 deaths) was not increased with available measures of radiation exposure and no significant associations were observed for acute, myelogenous, and monocytic leukemia (74 deaths). Relative to the general population, the standardized mortality ratio (SMR) for female breast cancer was 0.99 (based on 425 deaths); however, breast cancer was significantly elevated relative to all other cancers in a test of homogeneity of SMRs (ratio of SMRs = 1.3, P < 0.0001). Significant risks were correlated with employment before 1940 (SMR = 1.5; 95 percent confidence interval [CI] = 1.2-1.9), when radiation doses were likely highest, and among women certified for more than 30 years (SMR = 1.4, CI = 1.2-1.7) for whom the cumulative exposure was likely greatest. Using an internal referent group, risk increased with duration of certification among the 1,890 women certified before 1940 (P-trend < 0.001). While the findings for breast cancer are consistent with a radiation effect, possible misclassification in exposure (based on number of years certified) and potential confounding associated with reproductive histories preclude a causal conclusion.

Leukemia, lymphoma, and multiple myeloma following selected medical conditions.

The role of selected prior medical conditions in the etiology of hematopoietic malignancies was examined in a case-control study of members of two regional branches of the Kaiser Permanente Medical Care Program (USA). Past history of chronic infectious, autoimmune, allergic, and musculoskeletal disorders was abstracted from medical records for leukemia (n = 299), non-Hodgkin's lymphoma (NHL, n = 100), and multiple myeloma (n = 175) cases and matched controls (n = 787). Little difference was found between cases and controls for most of the chronic conditions evaluated, including sinusitis, carbuncles, urinary tract infections, pelvic infections, herpes zoster, asthma, rheumatoid arthritis, psoriasis, bursitis, and gout. Only three statistically significant elevated risks were found, i.e., with combined disc disease myeloma among patients with prior eczema and disk and other musculoskeletal conditions, and NHL following tuberculosis. Only two of these associations showed consistent patterns by sex and geographic region (myeloma with eczema and with musculoskeletal conditions). While prior history of eczema and musculoskeletal conditions may slightly increase risk of myeloma, this study provided little if any support for an association of chronic infectious, autoimmune, allergic, and musculoskeletal conditions with subsequent occurrence of the leukemias or NHL. Additionally, these data did not support a role for chronic antigenic stimulation, as defined in previous epidemiologic studies, in the etiology of hematopoietic malignancies.

Risks of non-Hodgkin's lymphoma, multiple myeloma, and leukemia associated with common medications.

We utilized data from two Kaiser Permanente medical care programs to evaluate risks of hematopoietic and lymphoproliferative (HLP) malignancies after use of 14 common medications. The subjects were adult cases of non-Hodgkin's lymphoma (NHL) (N = 94), multiple myeloma (N = 159), and leukemia (N = 257) and individually matched controls (N = 695). Abstractors reviewed medical records and recorded medication notations. Using a minimum 5-year exposure lag between first notation and malignancy diagnosis, the risk of NHL was greater among plan members who were prescribed amphetamines [odds ratio (OR) = 2.2; 95% confidence interval (CI) = 1.1-4.8], lidocaine (OR = 2.6; 95% CI = 1.2-5.5), and meprobamate (OR = 2.1; 95% CI = 1.03-4.3). The risk of NHL rose with increasing number of medical record notations for amphetamines; however, there was no association with number of notations for lidocaine or meprobamate. The odds ratio for total leukemia was decreased among patients who took chloramphenicol (OR = 0.4; 95% CI = 0.2-0.97).

Cancer mortality following treatment for adult hyperthyroidism. Cooperative Thyrotoxicosis Therapy Follow-up Study Group.

CONTEXT: High-dose iodine 131 is the treatment of choice in the United States for most adults with hyperthyroid disease. Although there is little evidence to link therapeutic (131)I to the development of cancer, its extensive medical use indicates the need for additional evaluation. OBJECTIVE: To evaluate cancer mortality among hyperthyroid patients, particularly after (131)I treatment. DESIGN: A retrospective cohort study. SETTING: Twenty-five clinics in the United States and 1 clinic in England. PATIENTS: A total of 35 593 hyperthyroid patients treated between 1946 and 1964 in the original Cooperative Thyrotoxicosis Therapy Follow-up Study; 91 % had Graves disease, 79% were female, and 65% were treated with (131)I. MAIN OUTCOME MEASURE: Standardized cancer mortality ratios (SMRs) after 3 treatment modalities for hyperthyroidism. RESULTS: Of the study cohort, 50.5% had died by the end of follow-up in December 1990. The total number of cancer deaths was close to that expected based on mortality rates in the general population (2950 vs 2857.6), but there was a small excess of mortality from cancers of the lung, breast, kidney, and thyroid, and a deficit of deaths from cancers of the uterus and the prostate gland. Patients with toxic nodular goiter had an SMR of 1.16 (95% confidence interval [CI], 1.03-1.30). More than 1 year after treatment, an increased risk of cancer mortality was seen among patients treated exclusively with antithyroid drugs (SMR, 1.31; 95% CI, 1.06-1.60). Radioactive iodine was not linked to total cancer deaths (SMR, 1.02; 95% CI, 0.98-1.07) or to any specific cancer with the exception of thyroid cancer (SMR, 3.94; 95% CI, 2.52-5.86). CONCLUSIONS: Neither hyperthyroidism nor (131)I treatment resulted in a significantly increased risk of total cancer mortality. While there was an elevated risk of thyroid cancer mortality following (131)I treatment, in absolute terms the excess number of deaths was small, and the underlying thyroid disease appeared to play a role. Overall, (131)I appears to be a safe therapy for hyperthyroidism.