Biomedical subjects
Alice Sigurdson
Publications and source records attributed to Alice Sigurdson.
Methods for etiologic and early marker investigations in the PLCO trial.
With the rapid development of biomarkers and new technologies, large-scale biologically-based cohort studies present expanding opportunities for population-based research on disease etiology and early detection markers. The prostate, lung, colorectal and ovarian cancer (PLCO) screening trial is a large randomized trial designed to determine if screening for these cancers leads to mortality reduction for these diseases. Within the Trial, the PLCO etiology and early marker study (EEMS) identifies risk factors for cancer and other diseases and evaluates biologic markers for the early detection of disease. EEMS includes 155,000 volunteers who provide basic risk factor information. Serial blood samples are collected at each of six screening rounds (including one collection for cryopreserved whole blood) from screening arm participants (77,000 subjects) and buccal cells are collected from those in the control arm of the trial. Etiologic studies consider environmental (e.g., diet), biochemical, and genetic factors. Early detection studies focus on blood-based biologic markers of early disease. Clinical epidemiology is also an important component of the PLCO trial.
A Ser49Cys variant in the ataxia telangiectasia, mutated, gene that is more common in patients with breast carcinoma compared with population controls.
BACKGROUND: Mothers of children who have ataxia telangiectasia have been reported to be at increased risk for development of breast carcinoma. To test whether sequence variants in the ataxia telangiectasia, mutated, gene (ATM) are associated with breast carcinoma, the authors compared the frequency of ATM cDNA sequence changes in patients with breast carcinoma with the corresponding frequency in control patients. METHODS: The authors sequenced ATM cDNA from 91 patients with breast carcinoma and compared the frequencies of sequence changes in these patients with the corresponding frequencies in a control sample of 940 individuals with no history of malignant disease. RESULTS: Thirty-five patients with breast carcinoma had one or more single-base changes in ATM. Three genetic variants were found in at least two patients. These variants resulted in Asp1853Asn, Pro1054Arg, or Ser49Cys amino acid substitutions in the ATM protein. The Ser49Cys variant was more common in patients with breast carcinoma than in the control patients, with respective frequencies of 6.7% (5 of 75 patients) and 1.3% (12 of 940 patients; P=0.006; Fisher two-sided exact test). The subgroup of patients with bilateral breast carcinoma had a Ser49Cys frequency of 11.8% (2 of 17 patients), which again was significantly different from what was observed in the control group (P=0.024; Fisher two-sided exact test). The allele frequencies of the other two variants were not different between case patients and control patients. CONCLUSIONS: Patients with breast carcinoma, particularly those with bilateral disease, were more likely to have a variant in the ATM gene that resulted in a Ser49Cys substitution in the gene product. Additional studies are needed to evaluate the potential functional consequences of the Ser49Cys substitution and confirm the relevance of this variant in the development of breast carcinoma.
Risk of melanoma among radiologic technologists in the United States.
Our study examines the risk of melanoma among medical radiation workers in the U.S. Radiologic Technologists (USRT) study. We evaluated 68,588 white radiologic technologists (78.8% female), certified during 1926-1982, who responded to a baseline questionnaire (1983-1989) and were free of cancer other than nonmelanoma skin at that time. Participants were followed through completion of a second questionnaire (1994-1998). We identified 207 cases, 193 subjects who reported first primary melanoma and 14 decedents with melanoma listed as an underlying or contributory cause of death. We examined risks of occupational radiation exposures using work history information on practices, procedures, and protective measures reported on the baseline questionnaire. Based on Cox proportional hazards regression, melanoma was significantly associated with established risk factors, including constitutional characteristics (skin tone, eye and hair color), personal history of nonmelanoma skin cancer, family history of melanoma and indicators of residential sunlight exposure. Melanoma risk was increased among those who first worked before 1950 (RR = 1.8, 95% CI = 0.6-5.5), particularly among those who worked 5 or more years before 1950 (RR = 2.4; 0.7-8.7; p (trend) for years worked before 1950 = 0.03), when radiation exposures were likely highest. Risk was also modestly elevated among technologists who did not customarily use a lead apron or shield when they first began working (RR = 1.4; 0.8-2.5). Clarifying the possible role of exposure to chronic ionizing radiation in melanoma is likely to require nested case-control studies within occupational cohorts, such as this one, which will assess individual radiation doses, and detailed information about sun exposure, sunburn history and skin susceptibility characteristics.
Risk of melanoma in relation to smoking, alcohol intake, and other factors in a large occupational cohort.
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.
Risk of basal cell carcinoma in relation to alcohol intake and smoking.
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.