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1.
Radiat Res ; 2010 May 17.
Article in English | MEDLINE | ID: mdl-20726733

ABSTRACT

Abstract In this paper, we describe recent methodological enhancements and findings from the dose reconstruction component of a study of cancer risks among U.S. radiologic technologists. An earlier version of the dosimetry published in 2006 (Simon et al., Radiat. Res. 166, 174-192, 2006) used physical and statistical models, literature-reported exposure measurements for the years before 1960, and archival personnel monitoring badge data from cohort members through 1984. The data and models were used to estimate unknown occupational radiation doses for 90,000 radiological technologists, incorporating information about each individual's employment practices based on a survey conducted in the mid-1980s. The dosimetry methods presented here, while using many of the same methods as before, now estimate annual and cumulative occupational badge doses (personal dose equivalent) to about 110,000 technologists for each year worked from 1916 to 2006, but with numerous methodological improvements. This dosimetry, using much more comprehensive information on individual use of protection aprons, estimates radiation absorbed doses to 12 organs and tissues (red bone marrow, ovary, colon, brain, lung, heart, female breast, skin of trunk, skin of head and neck and arms, testes, thyroid and lens of the eye). Every technologist's annual dose is estimated as a probability density function (pdf) to account for shared and unshared uncertainties. Major improvements in the dosimetry methods include a substantial increase in the number of cohort member annual badge dose measurements, additional information on individual apron use obtained from surveys conducted in the 1990s and 2005, refined modeling to develop annual badge dose pdfs using Tobit regression, refinements of cohort-based annual badge pdfs to delineate exposures of highly and minimally exposed individuals and to assess minimal detectable limits more accurately, and extensive refinements in organ dose conversion coefficients to account for uncertainties in radiographic techniques employed. For organ dose estimation, we rely on well-researched assumptions about critical exposure-related variables and their changes over the decades, including the peak kilovoltage and filtration typically used in conducting radiographic examinations and the usual body location for wearing radiation monitoring badges. We have derived organ dose conversion coefficients based on air-kerma weighting of photon fluences from published X-ray spectra and derived energy-dependent transmission factors for protective aprons of different thicknesses. We tailor bone marrow dose estimates to individual cohort members by using an individual-specific body mass index correction factor. To our knowledge the models and reconstructed doses presented herein represent the most comprehensive dose reconstructions undertaken for a cohort of medical radiation workers.

2.
Cancer Res ; 68(21): 8825-31, 2008 Nov 01.
Article in English | MEDLINE | ID: mdl-18974125

ABSTRACT

The U.S. population has nearly one radiographic examination per person per year, and concern about cancer risks associated with medical radiation has increased. Radiologic technologists were surveyed to determine whether their personal cumulative exposure to diagnostic X-rays was associated with increased frequencies of chromosome translocations, an established radiation biomarker and possible intermediary suggesting increased cancer risk. Within a large cohort of U.S. radiologic technologists, 150 provided a blood sample for whole chromosome painting and were interviewed about past X-ray examinations. The number and types of examinations reported were converted to a red bone marrow (RBM) dose score with units that approximated 1 mGy. The relationship between dose score and chromosome translocation frequency was assessed using Poisson regression. The estimated mean cumulative RBM radiation dose score was 49 (range, 0-303). After adjustment for age, translocation frequencies significantly increased with increasing RBM dose score with an estimate of 0.004 translocations per 100 cell equivalents per score unit (95% confidence interval, 0.002-0.007; P < 0.001). Removing extreme values or adjustment for gender, cigarette smoking, occupational radiation dose, allowing practice X-rays while training, work with radioisotopes, and radiotherapy for benign conditions did not affect the estimate. Cumulative radiation exposure from routine X-ray examinations was associated independently with increased chromosome damage, suggesting the possibility of elevated long-term health risks, including cancer. The slope estimate was consistent with expectation based on cytogenetic experience and atomic bomb survivor data.


Subject(s)
Occupational Exposure , Technology, Radiologic , Translocation, Genetic , Aged , Aged, 80 and over , Cohort Studies , Dose-Response Relationship, Radiation , Female , Humans , In Situ Hybridization, Fluorescence , Male , United States , Workforce
3.
Int J Cancer ; 123(11): 2713-6, 2008 Dec 01.
Article in English | MEDLINE | ID: mdl-18767034

ABSTRACT

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.


Subject(s)
Breast Neoplasms/epidemiology , Breast Neoplasms/genetics , DNA Repair/genetics , DNA/metabolism , Genetic Predisposition to Disease/genetics , Health Personnel/statistics & numerical data , Occupational Exposure/statistics & numerical data , Polymorphism, Genetic/genetics , Technology, Radiologic , Breast Neoplasms/metabolism , DNA/genetics , Female , Humans , Male , Radiation, Ionizing , Risk Factors , United States/epidemiology
4.
Am J Epidemiol ; 168(6): 620-31, 2008 Sep 15.
Article in English | MEDLINE | ID: mdl-18664497

ABSTRACT

The study aim was to determine the risk of cataract among radiologic technologists with respect to occupational and nonoccupational exposures to ionizing radiation and to personal characteristics. A prospective cohort of 35,705 cataract-free US radiologic technologists aged 24-44 years was followed for nearly 20 years (1983-2004) by using two follow-up questionnaires. During the study period, 2,382 cataracts and 647 cataract extractions were reported. Cigarette smoking for >or=5 pack-years; body mass index of >or=25 kg/m(2); and history of diabetes, hypertension, hypercholesterolemia, or arthritis at baseline were significantly (p or=3 x-rays to the face/neck was associated with a hazard ratio of cataract of 1.25 (95% confidence interval: 1.06, 1.47). For workers in the highest category (mean, 60 mGy) versus lowest category (mean, 5 mGy) of occupational dose to the lens of the eye, the adjusted hazard ratio of cataract was 1.18 (95% confidence interval: 0.99, 1.40). Findings challenge the National Council on Radiation Protection and International Commission on Radiological Protection assumptions that the lowest cumulative ionizing radiation dose to the lens of the eye that can produce a progressive cataract is approximately 2 Gy, and they support the hypothesis that the lowest cataractogenic dose in humans is substantially less than previously thought.


Subject(s)
Cataract/etiology , Occupational Exposure/adverse effects , Radiation, Ionizing , Smoking/adverse effects , Adult , Cohort Studies , Confidence Intervals , Dose-Response Relationship, Radiation , Female , Follow-Up Studies , Humans , Male , Middle Aged , Proportional Hazards Models , Risk Factors , Surveys and Questionnaires , United States/epidemiology
5.
Cancer Epidemiol Biomarkers Prev ; 17(4): 990-4, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18398043

ABSTRACT

The overwhelming majority of studies that have found increased cancer risk associated with functional deficits in DNA repair used a case-control design, in which measurements were made after cancer diagnosis. However, there are concerns about whether the cancer itself or cancer treatment affected the conclusions (reverse causation bias). We assessed the effect of cancer diagnosis among 26 breast cancer controls who had blood collected during 2001 to 2003 and again in 2005 to 2006 after being diagnosed with cancer. Using the alkaline comet assay, we quantified DNA damage in untreated lymphoblastoid cell lines. Comet distributed moment, olive tail moment, percentage of DNA in tail, and comet tail length were summarized as the geometric mean of 100 cells. For comet distributed moment, olive tail moment, tail DNA, and tail length, the proportions of women with before diagnosis values higher than after diagnosis were 65%, 50%, 50%, and 46%, respectively. We found no significant differences in the before or after diagnosis mean comet values. Median cut-points were determined from the before diagnosis distribution, and we used conditional logistic regression to calculate odds ratios (OR) and upper 95% bounds of the confidence intervals. ORs ranged from 0.6 to 0.9 with upper confidence interval bounds of 1.9 and 2.6, meaning biased ORs above 2.6 are unlikely. We found no evidence that reverse causation bias is an important concern in case-control studies using the comet assay applied to cell lines collected after cancer diagnosis. More work is needed to characterize the effect of cancer diagnosis on other phenotypic assays.


Subject(s)
DNA Damage , Neoplasms/diagnosis , Aged , Aged, 80 and over , Case-Control Studies , Comet Assay , Confidence Intervals , Female , Humans , Medical Records , Middle Aged , Neoplasms/blood
6.
Radiat Res ; 167(6): 727-34, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17523852

ABSTRACT

Measurement of chromosome translocations in peripheral blood lymphocytes has been used to quantify prior exposure to ionizing radiation, including for workers exposed to low, chronic doses. We assessed translocation frequencies in a subset of U.S. radiologic technologists to substantiate ionizing radiation dose estimates developed for 110,418 technologists who worked between 1916 and 1984. From 3,441 cohort members known to have begun working before 1950, we selected a sample of 152, stratified by estimated cumulative dose, over-sampling from higher-dose categories and excluding persons with a prior cancer diagnosis, a personal or family history of chromosomal instability disorders, or a current history of smoking. Estimates of film-badge dose ranged from less than 10 cSv to more than 30 cSv. Blood samples, obtained in 2004, were analyzed by fluorescence in situ hybridization (FISH) whole chromosome painting by simultaneously labeling chromosomes 1, 2 and 4 in red and 3, 5 and 6 in green. Translocations were scored in 1800 well-spread metaphase cells and expressed per 100 cell equivalents (CE) per person. Linear Poisson regression models with allowance for overdispersion were used to assess the relationship between estimated occupational red bone marrow absorbed dose in cGy and translocation frequency, adjusted for age, gender and estimated red bone marrow absorbed dose score from personal diagnostic procedures. We observed 0.09 excess translocations per 100 CE per cGy red bone marrow dose (95% CI: -0.01, 0.2; P = 0.07), which is similar to the expected estimate based on previous cytogenetic studies (0.05 excess translocations per 100 CE per cGy). Despite uncertainty in the estimates of occupational red bone marrow absorbed doses, we found good general agreement between the doses and translocation frequencies, lending support to the credibility of the dose assessment for this large cohort of U.S. radiologic technologists.


Subject(s)
Allied Health Personnel/statistics & numerical data , Biological Assay/statistics & numerical data , Occupational Exposure/analysis , Occupational Exposure/statistics & numerical data , Radiometry/statistics & numerical data , Technology, Radiologic , Translocation, Genetic/radiation effects , Aged , Aged, 80 and over , Biological Assay/methods , Body Burden , Female , Humans , Male , Radiation Dosage , Relative Biological Effectiveness , Retrospective Studies , Risk Assessment/methods , Risk Factors , Technology, Radiologic/statistics & numerical data , Translocation, Genetic/genetics , United States/epidemiology , Workforce
7.
Am J Epidemiol ; 166(1): 55-61, 2007 Jul 01.
Article in English | MEDLINE | ID: mdl-17426039

ABSTRACT

Inconsistent epidemiologic findings on cigarette smoking and female breast cancer risk may reflect insufficient assessment of smoking onset and amount relative to reproductive events. To determine the risk of breast cancer associated with smoking during different periods of reproductive life, the authors evaluated 906 incident breast cancer cases in a nationwide cohort of 56,042 female US radiologic technologists (1983-1998) who responded to two questionnaire surveys. After they accounted for age, birth cohort, and established breast cancer risk factors, smoking-related breast cancer risks differed by smoking during three reproductive time periods (p = 0.003), with a statistically significant 3% increase per pack-year of smoking between menarche and first childbirth (relative risk = 1.03, 95% confidence interval: 1.02, 1.05) and no significant association for smoking after first childbirth. Risk also increased with younger age at smoking initiation (p-trend = 0.06), after adjustment for pack-years of smoking before and after first childbirth, indicating an independent effect of age at smoking initiation. The findings from this study suggest that sensitivity of the female breast to tobacco carcinogens is increased during adolescence and early adulthood but decreases after first childbirth, when most breast tissue has terminally differentiated.


Subject(s)
Breast Neoplasms/etiology , Smoking/adverse effects , Adult , Aged , Confidence Intervals , Female , Health Surveys , Humans , Incidence , Middle Aged , Parity , Postmenopause , Pregnancy , Premenopause , Risk Factors , Surveys and Questionnaires , United States/epidemiology
8.
Pediatr Radiol ; 36 Suppl 2: 113-20, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16862404

ABSTRACT

With the exponential increase in minimally invasive fluoroscopically guided interventional radiologic procedures, concern has increased about the health effects on staff and patients of radiation exposure from these procedures. There has been no systematic epidemiologic investigation to quantify serious disease risks or mortality. To quantify all-cause, circulatory system disease and cancer mortality risks in U.S. radiologic technologists who work with interventional radiographic procedures, we evaluated mortality risks in a nationwide cohort of 88,766 U.S. radiologic technologists (77% female) who completed a self-administered questionnaire during 1994-1998 and were followed through 31 December 2003. We obtained information on work experience, types of procedures (including fluoroscopically guided interventional procedures), and protective measures plus medical, family cancer history, lifestyle, and reproductive information. Cox proportional hazards regression models were used to compute relative risks (RRs) with 95% confidence intervals (CIs). Between completion of the questionnaire and the end of follow-up, there were 3,581 deaths, including 1,209 from malignancies and 979 from circulatory system diseases. Compared to radiologic technologists who never or rarely performed or assisted with fluoroscopically guided interventional procedures, all-cause mortality risks were not increased among those working on such procedures daily. Similarly, there was no increased risk of mortality resulting from all circulatory system diseases combined, all cancers combined, or female breast cancer among technologists who daily performed or assisted with fluoroscopically guided interventional procedures. Based on small numbers of deaths (n=151), there were non-significant excesses (40%-70%) in mortality from cerebrovascular disease among technologists ever working with these procedures. The absence of significantly elevated mortality risks in radiologic technologists reporting the highest frequency of interventional radiography procedures must be interpreted cautiously in light of the small number of deaths during the relatively short follow-up. The present study cannot rule out increased risks of cerebrovascular disease, specific cancers, and diseases with low case-fatality rates or a long latency period preceding death.


Subject(s)
Neoplasms, Radiation-Induced/mortality , Occupational Diseases/mortality , Occupational Exposure/statistics & numerical data , Radiography, Interventional/mortality , Technology, Radiologic , Adult , Aged , Aged, 80 and over , Body Burden , Female , Humans , Incidence , Male , Middle Aged , Risk Assessment/methods , Risk Factors , Survival Analysis , Survival Rate , Technology, Radiologic/statistics & numerical data , United States/epidemiology , Workforce , Young Adult
9.
Radiat Res ; 166(1 Pt 2): 174-92, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16808606

ABSTRACT

Data have been collected and physical and statistical models have been constructed to estimate unknown occupational radiation doses among 90,000 members of the U.S. Radiologic Technologists cohort who responded to a baseline questionnaire during the mid-1980s. Since the availability of radiation dose data differed by calendar period, different models were developed and applied for years worked before 1960, 1960- 1976 and 1977-1984. The dose estimation used available film-badge measurements (approximately 350,000) for individual cohort members, information provided by the technologists on their work history and protection practices, and measurement and other data derived from the literature. The dosimetry model estimates annual and cumulative occupational badge doses (personal dose equivalent) for each technologist for each year worked from 1916 through 1984 as well as absorbed doses to organs and tissues including bone marrow, female breast, thyroid, ovary, testes, lung and skin. Assumptions have been made about critical variables including average energy of X rays, use of protective aprons, position of film badges, and minimum detectable doses. Uncertainty of badge and organ doses was characterized for each year of each technologist's working career. Monte Carlo methods were used to generate estimates of cumulative organ doses for preliminary cancer risk analyses. The models and predictions presented here, while continuing to be modified and improved, represent one of the most comprehensive dose reconstructions undertaken to date for a large cohort of medical radiation workers.


Subject(s)
Neoplasms, Radiation-Induced/epidemiology , Occupational Diseases/epidemiology , Occupational Exposure/analysis , Occupational Exposure/statistics & numerical data , Radiation Monitoring/methods , Risk Assessment/methods , Technology, Radiologic/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , Body Burden , Cohort Studies , Computer Simulation , Female , Humans , Male , Middle Aged , Models, Biological , Organ Specificity , Radiation Dosage , Radiation Monitoring/instrumentation , Radiation Monitoring/statistics & numerical data , Relative Biological Effectiveness , Reproducibility of Results , Risk Factors , Sensitivity and Specificity , United States/epidemiology
10.
Cancer ; 106(12): 2707-15, 2006 Jun 15.
Article in English | MEDLINE | ID: mdl-16639729

ABSTRACT

BACKGROUND: Studies of atomic bomb survivors and medically exposed populations have demonstrated an increased risk of breast cancer associated with acute or protracted, intermediate-dose or high-dose, ionizing radiation; however, the risks associated with low-dose and low-dose-rate (protracted) exposures are less certain. METHODS: The authors evaluated incident breast cancer risks from 1983 to 1998 according to employment characteristics and a 4-level proxy index for cumulative radiation exposure based on 2 mail surveys among 56,436 U.S. female radiologic technologists who were certified from 1925 to 1980, adjusting for established breast cancer risk factors. RESULTS: During follow-up, 1050 new breast cancer diagnoses were ascertained. Compared with radiologic technologists who began working in 1970 or later, adjusted breast cancer risks for those who first worked in the 1960s, 1950s, 1940s, from 1935 to 1939, and before 1935 were 1.0 (95% confidence interval [CI], 0.8-1.2), 1.2 (95% CI, 0.9-1.6), 1.0 (95% CI, 0.7-1.5), 1.8 (95% CI, 1.0-3.2), and 2.9 (95% CI, 1.3-6.2), respectively. The risk rose with the number of years worked before 1940 (P value for trend = .002) and was elevated significantly among those who began working before age 17 years (relative risk, 2.6; 95% CI, 1.3-5.1; 10 women) but was not related to the total years worked in the 1940s or later. Compared with technologists who had a Level 1 (minimal) proxy index for cumulative radiation exposure, breast cancer risks were 1.0 (95% CI, 0.9-1.2), 1.0 (95% CI, 0.7-1.3), and 1.5 (95% CI, 1.0-2.2), respectively, for technologists who had Level 2, Level 3, and Level 4 (highest) exposure. CONCLUSIONS: Breast cancer risk was elevated significantly in female radiologic technologists who experienced daily low-dose radiation exposures over several years that potentially resulted in appreciable cumulative exposure. The increased risk for total years worked before 1940, but not later, was consistent with decreasing occupational radiation exposures, improvements in radiation technology, and more stringent radiation protection standards over time.


Subject(s)
Breast Neoplasms/epidemiology , Breast Neoplasms/etiology , Neoplasms, Radiation-Induced/epidemiology , Occupational Exposure/adverse effects , Technology, Radiologic , Adult , Breast Neoplasms/diagnostic imaging , Confidence Intervals , Dose-Response Relationship, Radiation , Female , Humans , Incidence , Middle Aged , Neoplasms, Radiation-Induced/etiology , Proportional Hazards Models , Radiography , Retrospective Studies , Risk Factors , United States/epidemiology , Workforce
11.
Mutat Res ; 586(2): 173-88, 2005 Oct 03.
Article in English | MEDLINE | ID: mdl-16099702

ABSTRACT

Variation in the detection, signaling, and repair of DNA damage contributes to human cancer risk. To assess capacity to modulate endogenous DNA damage among radiologic technologists who had been diagnosed with breast cancer and another malignancy (breast-other, n=42), early-onset breast cancer (early-onset, age or=75% versus below the median, age-adjusted) was most consistently associated with the highest odds ratios in the breast-other, early-onset, and thyroid cancer groups (with risk increased 10-, 5- or 19-fold, respectively, with wide confidence intervals) and decreased risk among the hyper-normal group. For the other three comet measures, risk of breast-other was elevated approximately three-fold. Risk of early-onset breast cancer was mixed and risk of thyroid cancer ranged from null to a two-fold increase. The hyper-normal group showed decreased odds ratios for tail DNA and OTM, but not CDM. DNA damage, as estimated by all comet measures, was relatively unaffected by survival time, reproductive factors, and prior radiation treatment. We detected a continuum of endogenous DNA damage that was highest among cancer cases, less in controls, and suggestively lowest in hyper-normal individuals. Measuring this DNA damage phenotype may contribute to the identification of susceptible sub-groups. Our observations require replication in a prospective study with a large number of pre-diagnostic samples.


Subject(s)
Breast Neoplasms/epidemiology , DNA Damage , Thyroid Neoplasms/epidemiology , Analysis of Variance , Breast Neoplasms/genetics , Cell Line , Cohort Studies , Comet Assay , Disease Susceptibility/epidemiology , Female , Humans , Longevity , Male , Medical Laboratory Personnel , Middle Aged , Odds Ratio , Radiology , Risk Assessment , Surveys and Questionnaires , Thyroid Neoplasms/genetics , United States/epidemiology
12.
Int J Cancer ; 115(5): 828-34, 2005 Jul 10.
Article in English | MEDLINE | ID: mdl-15704092

ABSTRACT

Ionizing radiation (IR) is an established cause of nonmelanoma skin cancer, but there is uncertainty about the risk associated with chronic occupational exposure to IR and how it is influenced by ultraviolet radiation (UVR) exposure. We studied 1,355 incident cases with basal cell carcinoma (BCC) and 270 with squamous cell carcinoma (SCC) of the skin in a cohort of 65,304 U.S. white radiologic technologists who responded to the baseline questionnaire survey in 1983-1989 and the follow-up survey in 1994-1998. Cox's proportional-hazards model was used to estimate relative risks of BCC and SCC associated with surrogate measures of occupational exposure to IR and residential UVR exposure during childhood and adulthood, adjusted for potential confounders including pigmentation characteristics. Relative risks of BCC, but not of SCC, were elevated among technologists who first worked during the 1950s (RR = 1.42; 95% CI = 1.12-1.80), 1940s (RR = 2.04; 95% CI = 1.44-2.88) and before 1940 (RR = 2.16; 95% CI = 1.14-4.09), when IR exposures were high, compared to those who first worked after 1960 (p for trend < 0.01). The effect of year first worked on BCC risk was not modified by UVR exposure, but was significantly stronger among individuals with lighter compared to darker eye and hair color (p = 0.013 and 0.027, respectively). This study provides some evidence that chronic occupational exposure to IR at low to moderate levels can increase the risk of BCC, and that this risk may be modified by pigmentation characteristics.


Subject(s)
Carcinoma, Basal Cell/etiology , Carcinoma, Squamous Cell/etiology , Occupational Exposure , Radiation Injuries/etiology , Radiology , Skin Neoplasms/etiology , Adult , Aged , Allied Health Personnel , Carcinoma, Basal Cell/epidemiology , Carcinoma, Squamous Cell/epidemiology , Cohort Studies , Female , Humans , Male , Middle Aged , Radiation Injuries/epidemiology , Radiation, Ionizing , Risk Factors , Skin Neoplasms/epidemiology , Skin Pigmentation , Workforce
13.
Ann Epidemiol ; 15(2): 129-36, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15652718

ABSTRACT

PURPOSE: Cohort studies often conduct periodic follow-up interviews (or waves) to determine disease incidence since the previous follow-up and to update measures of exposure and confounders. The common practice of excluding nonrespondents from standardized incidence ratio (SIR) analyses of these cohorts can bias the estimates of interest if nonrespondents and respondents differ on important characteristics related to outcomes of interest. We propose an analytic approach to reduce the impact of nonresponse in the analyses of SIRs. METHODS: Logistic regression models controlling baseline information are used to estimate the propensity, or the probability of response; the reciprocals of these propensities are used as weights in the analysis of risk. This is illustrated in the analysis of 15 years of follow-up of a cohort of US radiologic technologists after an initial interview to assess the risk at several cancer sites from occupational radiation exposure. We use information from the baseline survey and certification records to compute the propensity of responding to the second survey. SIRs are computed using Surveillance, Epidemiology, and End Results (SEER) cancer incidence rates. Variances of the SIRs are estimated by a jackknife method that accounts for additional variability resulting from estimation of the weights. RESULTS: We find that, in this application, weighting alters point estimates and confidence limits only to a small degree, thus providing reassurance that the results are robust to nonresponse. This indicates that results from the analyses excluding the missing data may be slightly biased and weighting helps in reducing the nonresponse bias. CONCLUSION: This method is flexible, practical, easy to use with existing software, and is applicable to missing data from cohorts with baseline information on all subjects.


Subject(s)
Bias , Cohort Studies , Logistic Models , Data Interpretation, Statistical , Female , Follow-Up Studies , Humans , Incidence , Male , Neoplasms, Radiation-Induced/epidemiology , Occupational Exposure , Technology, Radiologic , Time Factors
14.
Radiology ; 233(2): 313-21, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15375227

ABSTRACT

Radiologists and radiologic technologists were among the earliest occupational groups exposed to ionizing radiation and represent a large segment of the working population exposed to radiation from human-made sources. The authors reviewed epidemiologic data on cancer risks from eight cohorts of over 270,000 radiologists and technologists in various countries. The most consistent finding was increased mortality due to leukemia among early workers employed before 1950, when radiation exposures were high. This, together with an increasing risk of leukemia with increasing duration of work in the early years, provided evidence of an excess risk of leukemia associated with occupational radiation exposure in that period. While findings on several types of solid cancers were less consistent, several studies provided evidence of a radiation effect for breast cancer and skin cancer. To date, there is no clear evidence of an increased cancer risk in medical radiation workers exposed to current levels of radiation doses. However, given a relatively short period of time for which the most recent workers have been followed up and in view of the increasing uses of radiation in modern medical practices, it is important to continue to monitor the health status of medical radiation workers.


Subject(s)
Leukemia, Radiation-Induced/epidemiology , Neoplasms, Radiation-Induced/epidemiology , Occupational Diseases/epidemiology , Radiology , Technology, Radiologic , Humans , Occupational Exposure
15.
BMC Cancer ; 4: 9, 2004 Mar 12.
Article in English | MEDLINE | ID: mdl-15113441

ABSTRACT

BACKGROUND: Subtle functional deficiencies in highly conserved DNA repair or growth regulatory processes resulting from polymorphic variation may increase genetic susceptibility to breast cancer. Polymorphisms in DNA repair genes can impact protein function leading to genomic instability facilitated by growth stimulation and increased cancer risk. Thus, 19 single nucleotide polymorphisms (SNPs) in eight genes involved in base excision repair (XRCC1, APEX, POLD1), BRCA1 protein interaction (BRIP1, ZNF350, BRCA2), and growth regulation (TGFss1, IGFBP3) were evaluated. METHODS: Genomic DNA samples were used in Taqman 5'-nuclease assays for most SNPs. Breast cancer risk to ages 50 and 70 were estimated using the kin-cohort method in which genotypes of relatives are inferred based on the known genotype of the index subject and Mendelian inheritance patterns. Family cancer history data was collected from a series of genotyped breast cancer cases (N = 748) identified within a cohort of female US radiologic technologists. Among 2,430 female first-degree relatives of cases, 190 breast cancers were reported. RESULTS: Genotypes associated with increased risk were: XRCC1 R194W (WW and RW vs. RR, cumulative risk up to age 70, risk ratio (RR) = 2.3; 95% CI 1.3-3.8); XRCC1 R399Q (QQ vs. RR, cumulative risk up to age 70, RR = 1.9; 1.1-3.9); and BRIP1 (or BACH1) P919S (SS vs. PP, cumulative risk up to age 50, RR = 6.9; 1.6-29.3). The risk for those heterozygous for BRCA2 N372H and APEX D148E were significantly lower than risks for homozygotes of either allele, and these were the only two results that remained significant after adjusting for multiple comparisons. No associations with breast cancer were observed for: APEX Q51H; XRCC1 R280H; IGFPB3 -202A>C; TGFss1 L10P, P25R, and T263I; BRCA2 N289H and T1915M; BRIP1 -64A>C; and ZNF350 (or ZBRK1) 1845C>T, L66P, R501S, and S472P. CONCLUSION: Some variants in genes within the base-excision repair pathway (XRCC1) and BRCA1 interacting proteins (BRIP1) may play a role as low penetrance breast cancer risk alleles. Previous association studies of breast cancer and BRCA2 N372H and functional observations for APEX D148E ran counter to our findings of decreased risks. Due to the many comparisons, cautious interpretation and replication of these relationships are warranted.


Subject(s)
Breast Neoplasms/genetics , DNA Repair , Genes, BRCA1 , Genetic Predisposition to Disease/genetics , Polymorphism, Single Nucleotide/genetics , Aged , Cohort Studies , Female , Genotype , Humans , Middle Aged , Retrospective Studies , Risk Assessment
16.
Cancer Epidemiol Biomarkers Prev ; 12(12): 1540-3, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14693751

ABSTRACT

We prospectively investigated whether alcohol intake and smoking affect the risk of basal cell carcinoma (BCC) in subjects from the United States Radiological Technologists (USRT) cohort study. We evaluated 68,371 radiological technologists certified during 1926-1982 who were free of cancer at the time they answered a first questionnaire (1983-1989) and who completed a second questionnaire (1994-1998). The first questionnaire provided baseline information on numerous risk factors, including smoking and alcohol intake, and the second provided self-reported cancer diagnoses. During 698,190 person-years of follow-up, we identified 1,360 cases of BCC: 1,036 in women and 324 in men. Cox proportional hazards regression indicated that the trend in BCC was significantly associated with increased alcohol intake (P for trend = 0.001). Compared with those who reported no alcohol consumption, those who drank <1-2, 3-6, 7-14, and >14 drinks/week had multivariate risks of 1.1 [95% confidence interval (CI), 0.9-1.3], 1.3 (95% CI, 1.1-1.5), 1.4 (95% CI, 1.2-1.7), and 1.0 (95% CI, 0.7-1.6), respectively. We found no clear association between smoking and BCC. This is the second large prospective study to report a significant but nonmonotonic trend in increased risk associated with alcohol consumption.


Subject(s)
Alcohol Drinking/adverse effects , Carcinoma, Basal Cell/diagnosis , Carcinoma, Basal Cell/epidemiology , Skin Neoplasms/diagnosis , Skin Neoplasms/epidemiology , Smoking/adverse effects , Adult , Age Distribution , Aged , Cohort Studies , Female , Humans , Incidence , Male , Middle Aged , Probability , Proportional Hazards Models , Prospective Studies , Risk Assessment , Sex Distribution , Survival Rate , United States/epidemiology
17.
Cancer Causes Control ; 14(9): 847-57, 2003 Nov.
Article in English | MEDLINE | ID: mdl-14682442

ABSTRACT

OBJECTIVE: To investigate whether smoking, alcohol intake, female hormonal or anthropometric factors affect melanoma risk. METHODS: Using Cox proportional hazards regression analyses, we analyzed 68,588 white subjects (79% female) from the US Radiologic Technologists (USRT) Study who were cancer-free (other than non-melanoma skin cancer) as of the first of two self-administered questionnaires. Follow-up covered 698, 028 person-years, with 207 cases of melanoma. RESULTS: We found that melanoma risk was not associated with height, weight or BMI, nor with age at menarche, menopausal status, use of hormone replacement therapy, parity, age at first birth or oral contraceptive use. Melanoma risk was elevated with increasing alcohol use (RR: 2.1: 95% CI: 0.9-4.8, for > 14 drinks/week compared to never drinking; (p(trend) = 0.08)). Smoking for long durations compared to never smoking was inversely related to melanoma risk (RR: 0.6; 0.3-1.3; > or = 30 years; p(trend) = 0.03), though risk was not associated with number of packs smoked per day. CONCLUSIONS: None of the anthropometric or female reproductive/hormonal factors evaluated were related to melanoma risk. It is unclear whether the positive association with alcohol intake and inverse association with smoking for long duration are causal. The alcohol and smoking findings warrant detailed assessment in studies with substantial statistical power where potential biases can be more fully evaluated.


Subject(s)
Alcohol Drinking/epidemiology , Melanoma/epidemiology , Occupational Health/statistics & numerical data , Skin Neoplasms/epidemiology , Smoking/epidemiology , Adult , Aged , Alcohol Drinking/adverse effects , Anthropometry , Cohort Studies , Female , Follow-Up Studies , Humans , Male , Melanoma/etiology , Middle Aged , Prevalence , Proportional Hazards Models , Risk Factors , Skin Neoplasms/etiology , Smoking/adverse effects , Surveys and Questionnaires , Technology, Radiologic , United States/epidemiology , Workforce
19.
Cancer ; 97(12): 3080-9, 2003 Jun 15.
Article in English | MEDLINE | ID: mdl-12784345

ABSTRACT

BACKGROUND: Workers exposed to low doses of radiation can provide information regarding cancer risks that are of public concern. However, characterizing risk at low doses requires large populations and ideally should include a large proportion of women, both of which rarely are available. METHODS: Among 90305 radiologic technologists in the U.S. (77% women) who were followed during 1983-1998, data concerning incident cancer occurrence was obtained from mailed questionnaires and from death records. Standardized incidence ratios (SIRs) were computed using age-specific, gender-specific, race-specific, and calendar year-specific cancer rates from the Surveillance, Epidemiology, and End Results Program. RESULTS: The SIR for all cancers in both genders combined was 1.04 (95% confidence interval [95% CI], 1.00-1.07; n = 3292 technologists). Female technologists had an elevated risk for all solid tumors combined (SIR = 1.06; 95% CI, 1.02-1.10; n = 2168 women) and for breast cancers (SIR = 1.16; 95% CI, 1.09-1.23; n = 970 women), melanoma (SIR = 1.66; 95% CI, 1.43-1.89; n = 181 women), and thyroid cancers (SIR = 1.54; 95% CI, 1.24-1.83; n = 107 women). Male technologists experienced a decreased risk for solid tumors (SIR = 0.92; 95% CI, 0.85-0.98; n = 755 men); however, melanoma (SIR = 1.39; 95% CI, 1.00-1.79; n = 56 men) and thyroid cancers (SIR = 2.23; 95% CI, 1.29-3.59; n = 17 men) were increased. Among both genders, the risks were decreased for buccal cavity/pharyngeal cancers (SIR = 0.73; 95% CI, 0.55-0.90; n = 54 technologists), rectal cancers (SIR = 0.62; 95% CI 0.48-0.76; n = 53 technologists), and lung cancers (SIR = 0.77, 95% CI, 0.70-0.85; n = 307 technologists). CONCLUSIONS: The elevated risk for breast cancer may have been related to occupational radiation exposure. The observed excesses of melanoma and thyroid cancers may reflect, at least in part, earlier detection among medical workers with easy access to health care.


Subject(s)
Neoplasms/epidemiology , Technology, Radiologic/statistics & numerical data , Adult , Cohort Studies , Female , Humans , Incidence , Male , Middle Aged , Occupational Exposure/adverse effects , Risk Factors , United States/epidemiology
20.
Am J Epidemiol ; 157(7): 643-51, 2003 Apr 01.
Article in English | MEDLINE | ID: mdl-12672684

ABSTRACT

In a follow-up study, only 64% of 126,628 US radiologic technologists completed a questionnaire during 1994-1997 after two mailings. The authors conducted a randomized trial of financial incentives and delivery methods to identify the least costly approach for increasing overall participation. They randomly selected nine samples of 300 nonresponders each to receive combinations of no, 1.00 US dollar, 2.00 US dollars, and 5.00 US dollars cash or check incentives delivered by first-class mail or Federal Express. Federal Express delivery did not achieve greater participation than first-class mail (23.2% vs. 23.7%). In analyses pooled across delivery methods, the response was significantly greater for the 2.00 US dollar bill (28.9%, 95% confidence interval (CI): 25.2, 32.7; p < 0.0001), 5.00 US dollars check (27.5%, 95% CI: 22.5, 33.0; p = 0.0001), 1.00 US dollar bill (24.6%, 95% CI: 21.2, 28.3; p = 0.0007), and 2.00 US dollars check (21.8%, 95% CI: 18.5, 25.3; p = 0.02) compared with no incentive (16.6%, 95% CI: 13.7, 19.9). The response increased significantly with increasing incentive amounts from 0.00 to 2.00 US dollars cash (p trend < 0.0001). The 2.00 US dollar bill achieved a 30% greater response than did a 2.00 US dollars check (p = 0.005). For incentives sent by first-class mail, the 5.00 US dollars check yielded 30% greater participation than did the 2.00 US dollars check (p = 0.07). A 1.00 US dollar bill, chosen instead of the 2.00 US dollars bill because of substantially lower overall cost and sent by first-class mail to the remaining 42,717 nonresponders, increased response from 64% to 72%.


Subject(s)
Motivation , Adult , Aged , Allied Health Personnel/psychology , Confidence Intervals , Epidemiologic Methods , Female , Humans , Male , Middle Aged , Postal Service , Surveys and Questionnaires/economics
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