Joseph L. Lyon

A Combined Analysis of North American Case-Control Studies of Residential Radon and Lung Cancer

Cohort studies have consistently shown underground miners exposed to high levels of radon to be at excess risk of lung cancer, and extrapolations based on those results indicate that residential radon may be responsible for nearly 10–15% of all lung cancer deaths per year in the United States. However, case-control studies of residential radon and lung cancer have provided ambiguous evidence of radon lung cancer risks. Regardless, alpha-particle emissions from the short-lived radioactive radon decay products can damage cellular DNA. The possibility that a demonstrated lung carcinogen may be present in large numbers of homes raises a serious public health concern. Thus, a systematic analysis of pooled data from all North American residential radon studies was undertaken to provide a more direct characterization of the public health risk posed by prolonged radon exposure. To evaluate the risk associated with prolonged residential radon exposure, a combined analysis of the primary data from seven large scale case-control studies of residential radon and lung cancer risk was conducted. The combined data set included a total of 4081 cases and 5281 controls, representing the largest aggregation of data on residential radon and lung cancer conducted to date. Residential radon concentrations were determined primarily by α-track detectors placed in the living areas of homes of the study subjects in order to obtain an integrated 1-yr average radon concentration in indoor air. Conditional likelihood regression was used to estimate the excess risk of lung cancer due to residential radon exposure, with adjustment for attained age, sex, study, smoking factors, residential mobility, and completeness of radon measurements. Although the main analyses were based on the combined data set as a whole, we also considered subsets of the data considered to have more accurate radon dosimetry. This included a subset of the data involving 3662 cases and 4966 controls with α-track radon measurements within the exposure time window (ETW) 5–30 yr prior to the index date considered previously by Krewski et al. (2005). Additional restrictions focused on subjects for which a greater proportion of the ETW was covered by measured rather than imputed radon concentrations, and on subjects who occupied at most two residences. The estimated odds ratio (OR) of lung cancer generally increased with radon concentration. The OR trend was consistent with linearity (p = .10), and the excess OR (EOR) was 0.10 per Bq/m3 with 95% confidence limits (−0.01, 0.26). For the subset of the data considered previously by Krewski et al. (2005), the EOR was 0.11 (0.00, 0.28). Further limiting subjects based on our criteria (residential stability and completeness of radon monitoring) expected to improve radon dosimetry led to increased estimates of the EOR. For example, for subjects who had resided in only one or two houses in the 5–30 ETW and who had α-track radon measurements for at least 20 yr of this 25-yr period, the EOR was 0.18 (0.02, 0.43) per 100 Bq/m3. Both estimates are compatible with the EOR of 0.12 (0.02, 0.25) per 100 Bq/m3 predicted by downward extrapolation of the miner data. Collectively, these results provide direct evidence of an association between residential radon and lung cancer risk, a finding predicted by extrapolation of results from occupational studies of radon-exposed underground miners. E. G. Létourneau and J. B. Schoenberg have retired; J. A. Stolwijk holds an emeritus position. We acknowledge the helpful input of the following individuals who served on the International Steering Committee for the North American combined analysis: Ken Chadwick (CEC Radiation Protection Program), Susan Conrath (U.S. Environmental Protection Agency), Sarah Darby (Oxford University), Evan Douple (U.S. National Academy of Sciences), Colin Muirhead (UK National Radiation Protection Board), and Susan Rose (U.S. Department of Energy). Salary support for Drs. Field, Lynch, and Steck was provided in part by grant numbers R01 ES05653 and P30 ES05605 from the National Institute of Environmental Health Sciences, NIH and grant number R01 CA85942 from the National Cancer Institute, NIH. This research was supported by grants from the Canadian Institutes of Health Research (formerly the Medical Research Council of Canada) and the Natural Sciences and Engineering Research Council of Canada to D. Krewski, who currently holds the NSERC/SSHRC/McLaughlin Chair in Population Health Risk Assessment at the University of Ottawa. Financial support for the meetings of the Analysis Team and the Steering Committee was also provided by Health Canada and the U.S. Department of Energy. We are grateful to Dr. Huixia Jiang for assistance with the combined analysis, and to Jackie Monaghan for technical assistance in preparing this report.

The incidence of fibromyalgia and its associated comorbidities: a population-based retrospective cohort study based on International Classification of Diseases, 9th Revision codes.

Background:The epidemiology of fibromyalgia is poorly defined. The incidence of fibromyalgia has not been determined using a large population base. Previous studies based on prevalence data demonstrated that females are 7 times more likely to have fibromyalgia than males and that the peak age for females is during the childbearing years. Objective:We have calculated the incidence rate of fibromyalgia in a large, stable population and determined the strength of association between fibromyalgia and 7 comorbid conditions. Methods:We conducted a retrospective cohort study of a large, stable health insurance claims database (62,000 nationwide enrollees per year). Claims from 1997 to 2002 were examined using the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes to identify fibromyalgia cases (ICD code 729.1) and 7 predetermined comorbid conditions. Results:A total of 2595 incident cases of fibromyalgia were identified between 1997 and 2002. Age-adjusted incidence rates were 6.88 cases per 1000 person-years for males and 11.28 cases per 1000 person-years for females. Females were 1.64 times (95% confidence interval = 1.59–1.69) more likely than males to have fibromyalgia. Patients with fibromyalgia were 2.14 to 7.05 times more likely to have one or more of the following comorbid conditions: depression, anxiety, headache, irritable bowel syndrome, chronic fatigue syndrome, systemic lupus erythematosus, and rheumatoid arthritis. Conclusion:Females are more likely to be diagnosed with fibromyalgia than males, although to a substantially smaller degree than previously reported, and there are strong associations for comorbid conditions that are commonly thought to be associated with fibromyalgia.

Cigarette Smoking: Risk Factor for Premature Facial Wrinkling

OBJECTIVE To determine if cigarette smoking is a risk factor for the development of premature facial wrinkling. DESIGN Cross-sectional study. SETTING Smoking cessation clinic and community. PATIENTS Convenience sample of 132 adult smokers and non-smokers in 1988. MEASUREMENTS A questionnaire was administered to quantify cigarette smoking and to obtain information about possibly confounding factors such as skin pigmentation, sun exposure, age, and sex. Wrinkling was assessed using photographs of the temple region, and a severity score based on predetermined criteria was assigned. A logistic regression model, which controlled for confounding variables, was developed to assess the risk for premature wrinkling in response to pack-years of smoking. MAIN RESULTS The prevalence of premature wrinkling was independently associated with sun exposure and pack-years of smoking. After controlling for age, sex, and sun exposure, premature wrinkling increased with increased pack-years of smoking. Heavy cigarette smokers (greater than 50 pack-years) were 4.7 times more likely to be wrinkled than nonsmokers (95% CI, 1.0 to 22.6; P value for trend = 0.05). Sun exposure of more than 50,000 lifetime hours also increased the risk of being excessively wrinkled 3.1-fold (CI, 1.2 to 7.1). When excessive sun exposure and cigarette smoking occurred together, the risk for developing excessive wrinkling was multiplicative (prevalence ratio of 12.0; CI, 1.5 to 530). CONCLUSION Cigarette smoking is an independent risk factor for the development of premature wrinkling.

Natural history of thyroid abnormalities: Prevalence, incidence, and regression of thyroid diseases in adolescents and young adults

PURPOSE This study reports the prevalence, incidence, and regression of thyroid abnormalities in a population observed from adolescence to adulthood. PATIENTS AND METHODS Examinations for thyroid abnormalities were performed in 4,819 school-age children, ages 11 to 18, in 1965 to 1968; two thirds of this original cohort (3,121) were re-examined 20 years later (1985 to 1986). Each subject with a thyroid abnormality detected by physical examination was studied by means of a series of re-examinations, and tests of thyroid function, imaging, and biopsy to determine the exact nature of the thyroid abnormality. RESULTS In the initial examinations (1965 to 1968), 185 thyroid abnormalities were found (3.7%). Diffuse hypertrophy with normal function (adolescent goiter) was the most common abnormality (19.3/1,000); 12.7/1,000 had chronic lymphocytic thyroiditis, and 4.6/1,000 had thyroid nodules, including two papillary carcinomas. Hyperthyroidism or hypothyroidism was found in 1.9/1,000. In the follow-up examinations in 1985 to 1986, 298 subjects had thyroid abnormalities (10.5%), of whom 81 (28.7/1,000) had simple goiters, 145 (51.3/1,000) had chronic thyroiditis, 45 (15.9/1,000) had hypothyroidism, 11 (3.9/1,000) had hyperthyroidism, and 66 (23.2/1,000) had nodules, which included 10 carcinomas. Of the 92 subjects with simple or adolescent goiter in 1965 to 1968, 60% were normal by 1985 to 1986, 20% were unchanged, and a few had developed thyroiditis (10%) or colloid goiters (3.0%). Of 61 subjects with thyroiditis, 27% had become normal, 33% remained unchanged, and 33% had become hypothyroid. Of the 22 subjects with thyroid nodules, two had complete disappearance of the nodules, and three had nodules considered to be variants of normal. The others exhibited a variety of nodular pathologic conditions. CONCLUSIONS The natural history of thyroid disorders, including simple goiter, chronic thyroiditis, hyperthyroidism, hypothyroidism, and nodular diseases of the thyroid, indicates they are dynamic and changeable in form, function, appearance, and disappearance.

Efficacy of the Ketogenic Diet as a Treatment Option for Epilepsy: Meta-analysis:

The evidence base for the efficacy of the ketogenic diet was assessed among pediatric epileptic patients by application of a rigorous statistical meta-analysis. Nineteen studies from 392 abstracts met the inclusion criteria. The sample size was 1084 patients (mean age at initiation 5.78 ± 3.43 years). The pooled odds ratio, using a random effects model, of treatment success (> 50% seizure reduction) among patients staying on the diet relative to those discontinuing the diet was 2.25 (95% confidence interval = 1.69—2.98). The reasons for diet discontinuation included < 50% seizure reduction (47.0%), diet restrictiveness (16.4%), and incurrent illness or diet side effects (13.2%). The results indicate that children with generalized seizures and patients who respond with > 50% seizure reduction within 3 months tend to remain on the diet longer. Although no class I or II studies have been published regarding the efficacy of the ketogenic diet, this meta-analysis shows that current observational studies reporting on the therapeutic effect of the ketogenic diet contain valuable statistical data. Future observational studies should aim for long-term follow-up, patient dropout analysis, and improved seizure type characterization. (J Child Neurol 2006;21:193—198; DOI 10.2310/7010.2006.00044).

Cellulitis incidence in a defined population.

A population-based insurance claims database was used to examine cellulitis incidence, anatomical sites of infection, complicating diagnoses, source of health service, and recurrence rates. Insurance claim files were searched for cellulitis ICD-9-CM codes 681.0-682.9. Complications of cellulitis including erysipelas, lymphadenitis, lymphangitis, and necrotizing fasciitis were also identified by ICD-9-CM codes. We found a cellulitis incidence rate of 24.6/1000 person-years, with a higher incidence among males and individuals aged 45-64 years. The most common site of infection was the lower extremity (39.9%). The majority of patients were seen in an outpatient setting (73.8%), and most (82.0%) had only one episode of cellulitis during the 5-year period studied. There was a very low incidence of cellulitis complications, including necrotizing fasciitis. Cellulitis is fairly common, usually treated in outpatient settings, and is infrequently complicated by erysipelas, lymphadenitis, lymphangitis, or necrotizing fasciitis.

Relationships between body mass indices and surgical replacements of knee and hip joints

BACKGROUND Osteoarthritis is both the most common form of arthritis and the most common reason for joint replacement surgery. Obese persons are believed to be more likely to develop generalized osteoarthritis that leads not only to knee but also to hip joint replacement surgeries. We hypothesized that obesity is also a risk for partial joint replacements and surgical revisions. METHODS A frequency-matched case-control study was conducted in Utah. Between 1992 and 2000, 840 hip and 911 knee joint replacement surgery patients, aged 55 to 74 years, were included in this study. Cases were randomly matched to 5578 controls, defined as Utah residents enrolled in a cancer screening trial. Odds ratios (ORs) were calculated using ICD-9 (International Classification of Diseases, 9th revision) procedural codes and body mass index (BMI) groups. RESULTS There was a strong association between increasing BMI and both total hip and knee replacement procedures. In males, the highest OR was for those weighing 37.50 to 39.99 kg/m(2) (total hip: OR=9.37, 95% confidence interval [CI] 2.64-33.31; total knee: OR=16.40; 95% CI 5, 19-51.86). In females, the highest OR was for those weighing > or =40 kg/m(2) (total hip: OR=4.47; 95% CI, 2.13-9.37; total knee: OR=19.05; 95% CI, 9.79-37.08). There were slight gender-specific differences in risk found for partial hip replacement procedures. Unexpectedly, no statistically significant association was found between obesity and the risk for hip or knee revision procedures. CONCLUSIONS While there is an association between obesity and hip and knee joint replacement surgeries, obesity does not appear to confer an independent risk for hip or knee revision procedures.

Occupational exposure to formaldehyde and wood dust and nasopharyngeal carcinoma

OBJECTIVES To investigate whether occupational exposures to formaldehyde and wood dust increase the risk of nasopharyngeal cancer (NPC). METHODS A multicentred, population based case-control study was carried out at five cancer registries in the United States participating in the National Cancer Institutes SEER program. Cases (n=196) with a newly diagnosed NPC between 1987 and 1993, and controls (n=244) selected over the same period from the general population through random digit dialing participated in structured telephone interviews which inquired about suspected risk factors for the disease, including a lifetime history of occupational and chemical exposure. Histological type of cancer was abstracted from clinical records of the registries. Potential exposure to formaldehyde and wood dust was assessed on a job by job basis by experienced industrial hygienists who were blinded as to case or control status. RESULTS For formaldehyde, after adjusting for cigarette use, race, and other risk factors, a trend of increasing risk of squamous and unspecified epithelial carcinomas was found for increasing duration (p=0.014) and cumulative exposure (p=0.033) but not for maximum exposure concentration. The odds ratio (OR) for people cumulatively exposed to >1.10 ppm-years was 3.0 (95% confidence interval (95% CI) 1.3 to 6.6) compared with those considered unexposed. In analyses limited to jobs considered definitely exposed, these trends became stronger. The associations were most evident among cigarette smokers. By contrast, there was no association between potential exposure to formaldehyde and undifferentiated and non-keratinising carcinomas. There was little evidence that exposure to wood dust increased risk of NPC, as modest crude associations essentially disappeared after control for potential exposure to formaldehyde. CONCLUSIONS These results support the hypothesis that occupational exposure to formaldehyde, but not wood dust, increases risk of NPC. This association seems to be specific to squamous cell carcinomas. Established cohorts of workers exposed to formaldehyde and wood dust should continue to be monitored for NPC and other respiratory cancers. Future studies of NPC should take into account histological type in assessing risk from environmental and host factors.

Cancer incidence in Mormons and non-Mormons in Utah, 1966-1970.

Abstract Between 1950 and 1969 cancer mortality in white Utah residents was 22 per cent less than that in the entire United States population. The religion of 72 per cent of the State residents (Mormon) proscribes use of tobacco and alcohol. We therefore analyzed the 10,641 cases of cancer identified in Utah from 1966 to 1970 and compared the incidence found in Utah Mormons, in Utah non-Mormons, and in a national survey. Comparison of Utah Mormons with non-Mormons showed that Mormons had a lower incidence of all cancers associated with cigarette smoking (P < 0.00001). Mormon females had a low incidence of cancer of the breast (P = 0.008), uterine cervix (P < 0.00001), and ovary (P = 0.04); Mormon males had a lower incidence of stomach cancers (P = 0.003). These findings add evidence to the association between cigarette smoking and certain cancers, but leave unexplained the significant differences between Mormons and non-Mormons for incidence of cancer of the breast, cervix, prostate and nervous system. (N...

The effect of age at smoking initiation on lung cancer risk

It has been assumed that a younger age at initiation of cigarette smoking is associated with an increased risk of lung cancer, but previous studies have not adjusted for two strong risk factors, the amount smoked and duration smoked. We used data from a population-based case-control study with 282 histologically confirmed lung cancer cases matched to 3,282 random controls to determine whether age at initiation of smoking plays an independent role in the occurrence of lung cancer. After controlling for age, sex, and amount of tobacco exposure, men who began to smoke before age 20 had a substantially higher risk of developing lung cancer [odds ratio (OR) = 12.7; 95% confidence interval (CI) = 6.39–25.2] compared with men who began smoking at age 20 or older (OR = 6.03; 95% CI = 2.82–12.9). For women, the heavy increase in risk continued until age 25 (OR = 9.97; 95% CI = 4.68–21.2) compared with women who began smoking at age 26 or older (OR = 2.58; 95% CI = 0.5312.4). There was no predisposition toward a specific histologic type of lung cancer. In this study, up to 52.4% of lung cancer cases in men and up to 73.0% of lung cancer cases in women could be attributed to this effect of early age of first smoking. (Epidemiology 1993; 4:444–448)