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Alice J Sigurdson

Publications and source records attributed to Alice J Sigurdson.

At least 19 recordsLinked to original sources
PubMed2007

Papillary thyroid cancer and polymorphic variants in TSHR- and RET-related genes: a nested case-control study within a cohort of U.S. radiologic technologists.

Several variants in the TSHR and RET signaling pathways genes have been reported to be related to cancer risk. We hypothesized that polymorphic variants in these genes are associated with the risk of papillary thyroid cancer. A nested case-control study was conducted within the U.S. Radiologic Technologists cohort. Eligible validated papillary thyroid cancer cases (n = 167) and frequency-matched (by sex and birth year) controls (n = 491) donated blood for analysis. There were no statistically significant associations between papillary thyroid cancer and 10 selected polymorphic variants in analyses of men and women combined. A borderline significant increasing risk was found for RET G691S (P(trend) = 0.05) and was especially pronounced among young women. For women under 38 years (the median age at diagnosis), the odds ratios were 2.1 (95% confidence interval, 1.2-3.7) for those heterozygous for the RET G691S polymorphism and 3.7 (95% confidence interval, 1.1-11.8) for those who were homozygous (P(trend) = 0.001). Our data provide limited evidence that TSHR- and RET-related genes are related to papillary thyroid cancer risk.

Adult↗
PubMed2006

Lung cancer risk among US radiologic technologists, 1983-1998.

While exposure to moderate to high-dose ionizing radiation is an established risk factor for lung cancer, the relationship between lung cancer and chronic low dose radiation remains uncertain. We examined lung cancer risk among 71,894 US radiologic technologists who were certified during 1926-1982, responded to a baseline questionnaire (1983-1989), and were free of cancer other than non-melanoma skin cancer at baseline. Study participants were followed until completion of a second questionnaire (1994-1998), death, or August 31, 1998. We identified 287 lung cancer cases: 66 incident cases and 221 decedents. Exposure to radiation was inferred based on work history information provided in the baseline questionnaire. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazard models adjusted for age, race/ethnicity and smoking. Smoking-adjusted lung cancer risk was not related to working as a radiologic technologist in early years when radiation exposures were likely highest (RR = 0.9; 95% CI, 0.5-1.8 for year first worked before 1940 compared to year first worked >or=1960), nor was risk related to the year first worked after 1940 or the number of years worked in any decade. While lung cancer risk was increased in radiologic technologists who held patients for X-rays, or who allowed others to take numerous practice X-rays on them, the trend was not statistically significant in either case. Although we adjusted for smoking, the possibility of residual confounding exists. Overall, we find very limited evidence that chronic low-to-moderate dose occupational exposure increased lung cancer risk in the US Radiologic Technologist cohort.

Adult↗
PubMed2006

Thyroid cancer and employment as a radiologic technologist.

The association between chronic occupational ionizing radiation exposure in the medical field and thyroid cancer is not well characterized. Thyroid cancer incidence was ascertained for 2 periods in a cohort of radiologic technologists certified for a minimum 2 years and enumerated in 1983: (i) cases identified prospectively in 73,080 radiologic technologists who were free of thyroid cancer at the baseline survey and completed a second questionnaire a decade later (N = 121), and (ii) cases occurring prior to cohort enumeration among 90,245 technologists who completed the baseline survey and were thyroid cancer free 2 years after certification (N = 148). Survival analyses estimated risks associated with employment as a radiologic technologist, including duration of employment, period of employment, types of procedures and work practices. The only occupational history characteristic associated with prospectively identified thyroid cancer was a history of holding patients for X-ray procedures at least 50 times (HR = 1.47, 95% CI = 1.01-2.15). Total years worked as a radiologic technologist, years performing diagnostic, therapeutic, and nuclear medicine procedures, employment under age 20 and calendar period of first employment were not associated with thyroid cancer risk. Risk of thyroid cancers diagnosed before the baseline questionnaire was inversely associated with decade first employed as a technologist, and was elevated, albeit imprecisely, among those working more than 5 years prior to 1950 (HR = 3.04, 95% CI = 1.01-10.78). These data provide modest evidence of an association between employment as a radiologic technologist and thyroid cancer risk; however, the findings require confirmation with more accurate exposure models.

Adult↗
PubMed2006

Candidate single nucleotide polymorphism selection using publicly available tools: a guide for epidemiologists.

Single nucleotide polymorphisms (SNPs) are the most common form of human genetic variation, with millions present in the human genome. Because only 1% might be expected to confer more than modest individual effects in association studies, the selection of predictive candidate variants for complex disease analyses is formidable. Technologic advances in SNP discovery and the ever-changing annotation of the genome have led to massive informational resources that can be difficult to master across disciplines. A simplified guide is needed. Although methods for evaluating nonsynonymous coding SNPs are known, several other publicly available computational tools can be utilized to assess polymorphic variants in noncoding regions. As an example, the authors applied multiple methods to select SNPs in DNA double-strand break repair genes. They chose to evaluate SNPs that occurred among a preexisting set of 57 validated assays and to justify new assay development for 83 potential SNPs in the DNA-dependent protein kinase catalytic subunit. Of the 140 SNPs, the authors eliminated 119 variants with low or neutral predictions. The existing computational methods they used and the semiquantitative relative ranking strategy they developed can be adapted to a priori SNP selection or post hoc evaluation of variants identified in whole genome scans or within haplotype blocks associated with disease. The authors show a "real world" application of some existing bioinformatics tools for use in large epidemiologic studies and genetic analyses. They also reviewed alternative approaches that provide related information.

Algorithms↗
PubMed2006

Breast cancer incidence in U.S. radiologic technologists.

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.

Adult↗
PubMed2006

The ATM missense mutation p.Ser49Cys (c.146C>G) and the risk of breast cancer.

Homozygous mutation in the ATM gene causes ataxia telangiectasia and heterozygous mutation carriers may be at increased risk of breast cancer. We studied a total of 22 ATM variants; 18 variants were analyzed in one of two large population-based studies from the U.S. and Poland, and four variants were analyzed in all 2,856 breast cancer cases and 3,344 controls from the two studies. The missense mutation Ser49Cys (c.146C>G, p.S49C), carried by approximately 2% of subjects, was more common in cases than controls in both study populations, combined odds ratio (OR) 1.69 (95% CI, 1.19-2.40; P=0.004). Another missense mutation at approximately 2% frequency, Phe858Leu (c.2572T>C, p.F858L), was associated with a significant increased risk in the U.S. study but not in Poland, and had a combined OR of 1.44 (95% CI, 0.98-2.11; P=0.06). These analyses provide the most convincing evidence thus far that missense mutations in ATM, particularly p.S49C, may be breast cancer susceptibility alleles. Because of their low frequency, even larger sample sizes are required to more firmly establish these associations.

Adult↗
PubMed2006

Interventional radiography and mortality risks in U.S. radiologic technologists.

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.

Adult↗
PubMed2006

The mortality risk of smoking and obesity combined.

BACKGROUND: Both smoking and obesity have been linked to increased mortality, but evaluating the joint effect has been limited. This nationwide, prospective mortality study of U.S. radiologic technologists was designed to evaluate the combined mortality risks of obesity and smoking. METHODS: Mortality risk was investigated in 64,120 women and 18,760 men who completed a baseline questionnaire (1983 to 1989). Body mass index (BMI) (weight adjusted for height, or kilograms divided by meters squared) was calculated from self-reported weight and height at baseline, with five categories: less than 18.5 (underweight), 18.5 to 24.9 (normal), 25.0 to 29.9 (overweight), 30.0 to 34.9 (moderately obese), and 35.0 and higher (very obese). Participants were followed from the questionnaire until the date of death or through 2002, whichever occurred first. The combined association among BMI and smoking and all-cause, cancer, and circulatory disease mortality by gender and attained age (less than 65 years, 65 years and older) was examined using Cox proportional hazards regression analyses (conducted in 2005). Person-years at risk averaged 16 years (women aged less than 65), 6 years (women aged 65 and older), 15 years (men aged less than 65), and 7 years (men aged 65 and older), totaling 1.35 million person-years. RESULTS: In all gender/age groups, both obesity and smoking, particularly current smoking, contributed substantially to all-cause mortality, with 3.5- to 5-fold risks for very obese, current smokers compared to normal weight, never smokers. Current smoking was the predominant risk factor for cancer mortality. Combining obesity with current smoking increased circulatory disease mortality by 6- to 11-fold for people aged less than 65 years, compared to normal weight, never smokers. Obese former smokers (less than 65 years) had notably lower risks. CONCLUSIONS: Obese smokers (aged less than 65 years) had strikingly high mortality risks, particularly from circulatory disease mortality.

Age Distribution↗
PubMed2006

Long-term storage and recovery of buccal cell DNA from treated cards.

Economical methods for collecting and storing high-quality DNA are needed for large population-based molecular epidemiology studies. Buccal cell DNA collected via saliva and stored on treated filter paper cards could be an attractive method, but modest DNA yields and the potential for reduced recovery of DNA over time were unresolved impediments. Consequently, buccal cell DNA collection via oral mouthwash rinsing became the method of choice in epidemiologic studies. However, the amount of genomic DNA (gDNA) required for genotyping continues to decrease, and reliable whole genome amplification (WGA) methods further reduced the mass of gDNA needed for WGA to 10 ng, diminishing the obstacle of low DNA yields from cards. However, concerns about yield and DNA quality over time remained. We located and analyzed 42 buccal cell saliva samples collected and stored on treated cards for 7 years at room temperature, -20 degrees C, and -80 degrees C. We recovered DNA from the treated cards, estimated the concentration by a human-specific quantitative real-time PCR assay, and evaluated the quality by PCR amplification of 268-, 536-, and 989-bp fragments of the beta-globin gene and by AmpFlSTR Identifiler assay analysis. Most DNA yields per 3-mm punch were <10 ng, and most PCR amplicons failed to amplify, where size of the amplicon was negatively associated with successful amplification. Using these methods, treated cards did not consistently provide sufficient quantities of buccal cell gDNA after 7 years of storage for genotyping or WGA.

DNA↗
PubMed2006

Thyroid cancer in childhood cancer survivors: a detailed evaluation of radiation dose response and its modifiers.

Radiation exposure at a young age is a strong risk factor for thyroid cancer. We conducted a nested case-control study of 69 thyroid cancer cases and 265 controls from a cohort of 14,054 childhood cancer survivors to evaluate the shape of the radiation dose-response relationship, in particular at high doses, and to assess modification of the radiation effects by patient and treatment characteristics. We considered several types of statistical models to estimate the excess relative risk (ERR), mainly guided by radiobiological models. A two-parameter model with a term linear in dose and a negative exponential in dose squared provided the best parsimonious description with an ERR of 1.3 per gray (95% confidence interval 0.4-4.1) at doses below 6 Gy and a relative decrease in ERR of 0.2% per unit dose squared with increasing dose, that is, decreases in the ERR/Gy of 53% at 20 Gy and 95% at 40 Gy. Further analyses using spline models suggested that the significant nonlinearity at high doses was characterized most appropriately as a true downturn rather than a flattening of the dose-response curve. We found no statistically significant modification of the dose-response relationship by patient characteristics; however, the linear parameter (i.e., the ERR/ Gy at doses less than 6 Gy) did decrease consistently and linearly with increasing age at childhood cancer diagnosis, from 4.45 for 0-1-year-olds to 0.48 for 15-20-year-olds. In summary, we applied models derived from radiobiology to describe the radiation dose-response curve for thyroid cancer in an epidemiological study and found convincing evidence for a downturn in risk at high doses.

Child↗
PubMed2005

DNA damage among thyroid cancer and multiple cancer cases, controls, and long-lived individuals.

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.

Analysis of Variance↗
PubMed2005

International patterns and trends in testis cancer incidence.

Although the incidence of testis cancer has risen markedly in many Western populations over the past half-century, it is not clear whether rates in other populations also have increased. To clarify this issue, we examined testis cancer incidence rates over the 25-year time period of 1973-1997 for selected populations around the world. Age-standardized incidence rates for 21 registries in the Americas, Asia, Europe and Oceania over successive 5-year time periods were obtained from volumes 4-8 of Cancer Incidence in Five Continents. Testis cancer rates rose between 1973 and 1997 in most populations worldwide, although the increases were strongest and most consistent among populations of European ancestry. Rates appear to be leveling off in some populations. The increases in testis cancer remain unexplained, although changes in the prevalence of important risk factors for this disease may be responsible.

Adolescent↗
PubMed2005

Nonmelanoma skin cancer in relation to ionizing radiation exposure among U.S. radiologic technologists.

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.

Adult↗
PubMed2005

An application of a weighting method to adjust for nonresponse in standardized incidence ratio analysis of cohort studies.

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.

Bias↗
PubMed2005

Genetic variation and willingness to participate in epidemiologic research: data from three studies.

The differences in common genetic polymorphism frequencies by willingness to participate in epidemiologic studies are unexplored, but the same threats to internal validity operate as for studies with nongenetic information. We analyzed single nucleotide polymorphism genotypes, haplotypes, and short tandem repeats among control groups from three studies with different recruitment designs that included early, late, and never questionnaire responders, one or more participation incentives, and blood or buccal DNA collection. Among 2,955 individuals, we compared 108 genotypes, 8 haplotypes, and 9 to 15 short tandem repeats by respondent type. Among our main comparisons, single nucleotide polymorphism genotype frequencies differed significantly (P < 0.05) between respondent groups in six instances, with 13 expected by chance alone. When comparing the odds of carrying a variant among the various response groups, 19 odds ratios were </=0.70 or >/=1.40, levels that might be notably different. Among the various respondent group comparisons, haplotype and short tandem repeat frequencies were not significantly different by willingness to participate. We observed little evidence to suggest that genotype differences underlie response characteristics in molecular epidemiologic studies, but a greater variety of genes should be examined, including those related to behavioral traits potentially associated with willingness to participate. To the extent possible, investigators should evaluate their own genetic data for bias in response categories.

Community Participation↗