The Association Between Tobacco Use and Risk of COVID-19 Infection and Clinical Outcomes in Sweden: A Population-Based Study.

Background: The association between tobacco use and COVID-19 is controversial. During the early course of the pandemic, limited testing prevented studying a wide spectrum of clinical manifestations. Objective: To examine the potential causal association between tobacco use and COVID-19 during the second wave (1 October 2020-30 June 2021) of the pandemic in Stockholm, Sweden. Methods: A population-based cohort study was conducted in the Stockholm region of Sweden, with information on tobacco use collected prior to the pandemic. Adjusted relative risks (RR) of COVID-19 and 95% confidence intervals (CI) were calculated, contrasting current smokers and snus users to non-users of tobacco. Results: Compared with non-users of tobacco, current smokers had a lower risk of COVID-19 (RR 0.78, 95% CI = 0.75-0.81) and of hospitalisation for the disease. Current snus users had a higher risk of COVID-19. Heavy smokers and snus users had longer hospital stays than non-users of tobacco. Conclusion: Tobacco use may have a different impact on the risk of being infected with SARS-CoV-2 and the risk of developing severe clinical manifestations. Further research is needed to determine the underlying mechanisms.

Current tobacco use and COVID-19 diagnoses in a cohort of adult clients of public dental clinics in Sweden.

Smoking has been linked with both increased and decreased risk of COVID-19, prompting the hypothesis of a protective role of nicotine in the pathogenesis of the disease. Studies of the association between use of smokeless tobacco and COVID-19 would help refining this hypothesis. We analysed data from 424,386 residents in the Stockholm Region, Sweden, with information on smoking and smokeless tobacco (snus) use prior to the pandemic obtained from dental records. Diagnoses of COVID-19 between February and October 2020 were obtained from health-care registers. We estimated the risk of receiving a diagnosis of COVID-19 for current smokers and for current snus users relative to non-users of tobacco, adjusting for potential confounders (aRR). The aRR of COVID -19 was elevated for current snus users (1.09 ;95%CI = 0.99-1.21 among men and 1.15; 95%CI = 1.00-1.33 among women). The risk for women consuming more than 1 can/day was twice as high as among non-users of tobacco. Current smoking was negatively associated with risk of COVID-19 (aRR = 0.68; 95% CI = 0.61-0.75); including hospital admission (aRR = 0.60; 95% CI = 0.47-0.76) and intensive care (aRR = 0.43; 95% CI = 0.21-0.89). The hypothesis of a protective effect of tobacco nicotine on COVID-19 was not supported by the findings. The negative association between smoking and COVID-19 remains unexplained.

Increasing Children's physical Activity by Policy (CAP) in preschools within the Stockholm region: study protocol for a pragmatic cluster-randomized controlled trial.

BACKGROUND: Systematic reviews suggest that preschool environmental/organizational changes may be effective in increasing physical activity (PA) levels of preschool children, but evidence is scarce regarding feasible, effective, and equitable interventions that can be scaled up. Specifically, it is essential to understand whether introducing a multicomponent organizational change in terms of policy in the preschool context may be beneficial for children's PA levels and concomitant health outcomes. To bridge this knowledge gap, our main aim is to examine the feasibility and effectiveness of a policy package in increasing PA levels in preschool children, using a large-scale pragmatic cluster-randomized controlled trial. METHODS: This proposed study is a pragmatic cluster-randomized controlled trial with two conditions (intervention and control with a 1:1 ratio) with preschools as clusters and the unit of randomization. We aim to recruit approximately 4000 3-5-year-old children from 90 preschools and retain more than 2800 children from 85 preschools to provide adequate statistical power for the analyses. The intervention to implement is a co-created, multicomponent policy package running for 6 months in preschools randomized to intervention. Change in accelerometer measured PA levels in children between intervention and control from pre- and post-intervention will be the primary outcome of the study, while secondary outcomes include health outcomes such as musculoskeletal fitness, psychosocial functioning, and absence due to illness in children among others. Implementation will be studied carefully using both quantitative (dose, fidelity) and qualitative (interview) methodologies. The change in primary and secondary outcomes, from pre- to post-intervention, will be analyzed with linear mixed-effect models (to allow both fixed and random effects) nested on a preschool level. DISCUSSION: This is a large-scale co-creation project involving the City of Stockholm, childcare stakeholders, preschool staff, and the research group with the potential to influence more than 30,000 preschool children within the Stockholm area. The study will add reliable evidence for the implementation of PA policies at the organizational level of preschools and clarify its potential effect on objectively measured PA and health markers in children. TRIAL REGISTRATION: ClinicalTrials.gov NCT04569578 . Prospectively registered on September 20, 2020.

Effectiveness of interventions on physical activity in overweight or obese children: a systematic review and meta-analysis including studies with objectively measured outcomes.

There is no consensus on interventions to be recommended in order to promote physical activity among overweight or obese children. The objective of this review was to assess the effects on objectively measured physical activity, of interventions promoting physical activity among overweight or obese children or adolescents, compared to no intervention or to interventions without a physical activity component. Publications up to December 2015 were located through electronic searches for randomized controlled trials resulting in inclusion of 33 studies. Standardized mean differences from baseline to post-intervention and to long-term follow-up were determined for intervention and control groups and meta-analysed using random effects models. The meta-analysis showed that interventions had no effect on total physical activity of overweight and obese children, neither directly post-intervention (-0.02 [-0.15, 0.11]) nor at long-term follow-up (0.07 [-0.27, 0.40]). Separate analyses by typology of intervention (with or without physical fitness, behavioural or environmental components) showed similar results (no effect). In conclusion, there is no evidence that currently available interventions are able to increase physical activity among overweight or obese children. This questions the contribution of physical activity to the treatment of overweight and obesity in children in the studied interventions and calls for other treatment strategies.

Snus (Swedish smokeless tobacco) use and risk of stroke: pooled analyses of incidence and survival.

BACKGROUND: Snus is a moist smokeless tobacco product with high nicotine content. Its use has a short-term effect on the cardiovascular system, but the relationship between snus use and stroke is unclear. OBJECTIVE: The aim of this study was to assess the associations between use of snus and incidence of and survival after stroke, both overall and according to subtypes. METHODS: Pooled analyses of eight Swedish prospective cohort studies were conducted, including 130 485 men who never smoked. We estimated hazard ratios (HRs) with 95% confidence intervals (CIs) of incidence and death after diagnosis using Cox proportional hazard regression models and case fatality and survival using logistic regression and Kaplan-Meier methods, respectively. RESULTS: No associations were observed between the use of snus and the risk of overall stroke (HR 1.04, 95% CI 0.92-1.17) or of any of the stroke subtypes. The odds ratio (OR) of 28-day case fatality was 1.42 (95% CI 0.99-2.04) amongst users of snus who had experienced a stroke, and the HR of death during the follow-up period was 1.32 (95% CI 1.08-1.61). CONCLUSION: Use of snus was not associated with the risk of stroke. Hence, nicotine is unlikely to contribute importantly to the pathophysiology of stroke. However, case fatality was increased in snus users, compared with nonusers, but further studies are needed to determine any possible causal mechanisms.

Effect of Swedish snuff (snus) on preterm birth.

OBJECTIVE: To compare the effects of Swedish snuff and cigarette smoking on risks of preterm birth. DESIGN: Population-based cohort study. SETTING: Sweden. POPULATION: All live, singleton births in Sweden 1999-2006. METHODS: Odds ratios (OR) with 95% confidence intervals (CI) were used to estimate relative risks for preterm birth in snuff users (n = 7607), light smokers (1-9 cigarettes/day; n = 41 436) and heavy smokers (ten or more cigarettes/day; n = 16 951) using non-tobacco users (n = 503 957) as reference. MAIN OUTCOME MEASURES: Very (<32 weeks) and moderately (32-36 weeks) preterm birth. RESULTS: Compared with non-tobacco users, snuff users had increased risks of both very (adjusted OR 1.38; 95% CI 1.04-1.83) and moderately (adjusted OR 1.25; 95% CI 1.12-1.40) preterm birth. Compared with non-tobacco users, light smokers had increased risks of both very (adjusted OR 1.60; 95% CI 1.42-1.81) and moderately (adjusted OR: 1.18; 95% CI: 1.12-1.24) preterm birth, and heavy smokers had even higher risks. Among smokers, but not among snuff users, the risk was more pronounced for spontaneous than induced preterm birth. CONCLUSIONS: The use of Swedish snuff was associated with increased risks of very and moderately preterm birth with both spontaneous and induced onsets. Swedish snuff is not a safe alternative to cigarette smoking during pregnancy.

Use of snus and risk for cardiovascular disease: results from the Swedish Twin Registry.

OBJECTIVE: To study the association between snus use and the risk for cardiovascular disease, i.e. ischemic heart disease and stroke. DESIGN: Cohort study. SETTING: Sweden. SUBJECTS: Sixteen thousand six hundred and forty-two male Swedish twins participating in the Screening Across the Lifespan Twin Study, conducted in 1998- 2002, were followed for incident cardiovascular disease. Participants were without a history of cardiovascular disease at baseline and incident cases were identified via the Swedish Cause of Death Register and Hospital Discharge Register. RESULTS: Overall, there was no association between use of snus and risk for cardiovascular disease. Current snus users, without a smoking history, had a relative risk of 1.00 (95% confidence interval 0.69-1.46) for cardiovascular disease as compared to non users. Corresponding relative risks for ischemic heart disease and stroke were 0.85 (95% confidence interval 0.51-1.41) and 1.18 (95% confidence interval 0.67-2.08), respectively. In smoking adjusted models, risk estimates for ischemic heart disease in relation to snus use were all close to unity regardless of timing or intensity of snus use. However, current heavy snus users (consuming more than four cans week(-1)) had a relative risk for stroke of 1.75 (95% confidence interval 0.95-3.21). CONCLUSION: These data do not support any strong association between snus use and risk for cardiovascular disease.

Is universal prevention against youths' substance misuse really universal? Gender-specific effects in the EU-Dap school-based prevention trial.

BACKGROUND: Studies of effectiveness of school-based prevention of substance misuse have generally overlooked gender differences. The purpose of this work was to analyse gender differences in the effectiveness of a new European school-based curriculum for prevention of substance misuse among adolescents. METHODS: The European Drug Abuse Prevention (EU-Dap) trial took place in seven European countries during the school year 2004-05. Schools were randomly assigned to either a control group or a 12-session standardised curriculum ("Unplugged") based on a comprehensive social influence model. The analytical sample consisted of 6359 students (3324 boys and 3035 girls). The use of cigarettes, alcohol and illicit drugs, adolescents' knowledge and opinions about substances, as well as social and personal skills were investigated through a self-completed anonymous questionnaire administered at enrollment and 3 months after the end of the programme. Adjusted Prevalence Odds Ratios were calculated as the measure of association between the intervention and behavioural outcomes using multilevel regression modelling. RESULTS: At enrollment, boys were more likely than girls to have used cannabis and illicit drugs, whereas girls had a higher prevalence of cigarette smoking. At the follow-up survey, a significant association between the programme and a lower prevalence of all behavioural outcomes was found among boys, but not among girls. Age and self-esteem emerged as possible modifiers of these gender differences, but effects were not statistically significant. CONCLUSIONS: Comprehensive social influence school curricula against substance misuse in adolescence may perform differently among girls and boys, owing to developmental and personality factors.

Quitting cigarettes completely or switching to smokeless tobacco: do US data replicate the Swedish results?

BACKGROUND: Swedish male smokers are more likely than female smokers to switch to smokeless tobacco (snus) and males' smoking cessation rate is higher than that of females. These results have fuelled international debate over promoting smokeless tobacco for harm reduction. This study examines whether similar results emerge in the United States, one of few other western countries where smokeless tobacco has long been widely available. METHODS: US DATA SOURCE: national sample in Tobacco Use Supplement to Current Population Survey, 2002, with 1-year follow-up in 2003. Analyses included adult self-respondents in this longitudinal sample (n = 15,056). Population-weighted rates of quitting smoking and switching to smokeless tobacco were computed for the 1-year period. RESULTS: Among US men, few current smokers switched to smokeless tobacco (0.3% in 12 months). Few former smokers turned to smokeless tobacco (1.7%). Switching between cigarettes and smokeless tobacco, infrequent among current tobacco users (<4%), was more often from smokeless to smoking. Men quit smokeless tobacco at three times the rate of quitting cigarettes (38.8% vs 11.6%, p<0.001). Overall, US men have no advantage over women in quitting smoking (11.7% vs 12.4%, p = 0.65), even though men are far likelier to use smokeless tobacco. CONCLUSION: The Swedish results are not replicated in the United States. Both male and female US smokers appear to have higher quit rates for smoking than have their Swedish counterparts, despite greater use of smokeless tobacco in Sweden. Promoting smokeless tobacco for harm reduction in countries with ongoing tobacco control programmes may not result in any positive population effect on smoking cessation.

Cigarette smoking and the risk of goitre and thyroid nodules amongst parous women.

OBJECTIVES: To clarify the mechanisms by which smoking is associated to toxic and nontoxic goitre and thyroid nodules. DESIGN: Cohort study. SETTING: Sweden. SUBJECTS: A cohort of 874,507 parous women identified through the Medical Birth Registry, with smoking behaviour assessed through self-reported information at the first pre-natal visit, and follow-up between 1983 and 1997. MAIN OUTCOME MEASURES: Hospital diagnoses of toxic and nontoxic goitre and thyroid nodules, identified by record-linkage with the national Inpatient Registry. Cox regression was employed to estimate the hazard ratio (HR) of smokers compared with nonsmokers and the corresponding 95% confidence limits (CL). RESULTS: There was a significantly increased risk of goitre and nodules amongst smokers. The positive association was stronger for toxic (age adjusted HR = 1.94, CL = 1.74-2.16) than for nontoxic goitre and nodules (age-adjusted HR = 1.26; CL = 1.14-1.38). There was generally no clear risk trend with regard to amount smoked (below and above 10 cigarettes per day). Elevated body mass attenuated these associations, whilst being born in Swedish areas of endemic goitre enhanced the association with nontoxic goitre and nodules. CONCLUSIONS: Smoking enhances the risk of thyroid goitre and nodules requiring hospital admission. Iodine deficiency and body weight are likely to be important modifiers of the risk of thyroid hyperplastic diseases amongst smokers.

Validity of self reports in a cohort of Swedish adolescent smokers and smokeless tobacco (snus) users.

OBJECTIVE: To validate self reports of cigarette and smokeless tobacco (snus) use in a prospective cohort of adolescents. DESIGN: A cross sectional analysis of a cohort sub-sample. SETTING: County of Stockholm, Sweden. SUBJECTS: 520 adolescents in the final grade of junior high school (mean age 15.0 years). MAIN OUTCOME MEASURE: Concordance between self reported tobacco use and saliva cotinine concentration. RESULTS: Using a cut point of 5 ng/ml saliva cotinine to discriminate active tobacco use, there was a 98% concordance between self reported non-use in the past month and cotinine concentration. The sensitivity of the questionnaire compared to the saliva cotinine test, used as the gold standard, was 90% and the specificity 93%. One hundred and fifteen out of 520 subjects (22%) reported monthly tobacco use. Among these, 67% (46/69) of the exclusive cigarette smokers, 82% (23/28) of exclusive snus users, and 94% (15/16) of mixed users (cigarettes + snus) had cotinine concentrations above 5 ng/ml. Among subjects reporting daily use 96% (64/67) had saliva cotinine concentrations above the cut point. Exclusive current cigarette users were more likely to be classified discordantly by questionnaire and cotinine test compared to snus users (odds ratio 3.2, 95% confidence interval 1.2 to 8.6). CONCLUSION: This study confirms the reliability of adolescents' self reported tobacco use. In a context of low exposure to environmental tobacco smoke a cut off for saliva cotinine of 5 ng/ml reliably discriminated tobacco users from non-users. Irregular use of tobacco in this age group probably explains the discrepancy between self reported use and cotinine concentrations.

Smoking mothers and snuffing fathers: behavioural influences on youth tobacco use in a Swedish cohort.

OBJECTIVE: To analyse the influences of parental use of cigarettes and snus (the Swedish variety of smokeless tobacco) on offspring's behaviour. DESIGN: Prospective cohort study. SETTING: The Stockholm County of Sweden. SUBJECTS: 2232 adolescents recruited in the fifth grade (mean age 11.6 years) with follow up in the eighth grade. MAIN OUTCOME MEASURES: Self reported tobacco use (ever and current use of cigarettes and/or snus) in the eighth grade. RESULTS: Parents' tobacco use was associated with adolescents' current use of cigarettes and snus (odds ratio (OR) 2.7, 95% confidence interval (CI) 1.8 to 3.9 if both parents used tobacco v neither parent). Mother's cigarette smoking was associated with adolescents' current exclusive smoking (OR 2.4, 95% CI 1.6 to 3.6). Father's use of snus was associated with current exclusive use of snus among boys (OR 3.0, 95% CI 1.4 to 6.4), but not with current cigarette use. The overall prevalence of current smoking was lower among children whose fathers used snus than among those whose fathers smoked. CONCLUSIONS: Parental smoking, especially maternal smoking, enhances the risk of tobacco experimentation in youths, as does paternal use of smokeless tobacco. However, the transition to regular cigarette smoking is not likely to be affected by paternal use of smokeless tobacco. Contextual factors, in particular declining smoking trends and negative social acceptance of smoking, can explain most of these findings.

Between harm and dangers. Oral snuff use, cigarette smoking and problem behaviours in a survey of Swedish male adolescents.

BACKGROUND: The prevalence of smokeless tobacco use (moist snuff) in Sweden is among the highest world-wide, and snuff is gaining popularity as a less harmful alternative to cigarettes. METHODS: Patterns of current tobacco use and indicators of behavioural problems were analysed in a sample of 6287 boys participating in a census survey among 9th graders in Stockholm County, Sweden. RESULTS: Among participants reporting current use of oral snuff (OS) the majority (71%) also smoked cigarettes. The prevalence of daily smoking was significantly higher in this group than among exclusive smokers. Conditionally on smoking behaviour, the likelihood of being a current user of OS was several times higher among boys who had ever been drunk (adjusted odds ratio = 9.64, 95% confidence interval: 7.32-12.94) or experimented with illicit drugs (adjusted odds ratio = 2.39, 95% confidence interval: 1.99-2.87), compared with those who did not. OS use was also significantly associated to other problem behaviours such as drinking and driving, unsafe sex, and school truancy. The same pattern of associations was present when the analyses were restricted to tobacco users. CONCLUSIONS: Smokeless tobacco use in adolescence does not substitute cigarette smoking and can be an indicator of a drug- and risk-seeking lifestyle. The availability of smokeless tobacco might thus increase the potential for nicotine addiction in some vulnerable subgroups of young males.

A pooled analysis of case-control studies of thyroid cancer. VI. Fish and shellfish consumption.

OBJECTIVE: To better understand the role of fish and shellfish on thyroid cancer risk, we systematically re-analyzed the original data from 13 case-control studies conducted in the US, Japan, China, and Europe. METHODS: A total of 2497 cases (2023 women, 474 men) and 4337 controls (3268 women, 1069 men) were considered. Odds ratio (OR) and corresponding 95% confidence interval (CI) were estimated for each study by logistic regression models, conditioned on age and sex, and adjusted for history of goiter, thyroid nodules or adenomas, and radiation. Combined ORs were computed as the weighted average of the estimates from each study. RESULTS: The ORs for the highest level of total fish consumption (three or more times per week) as compared to the lowest one (less than once per week) was above unity in Hawaii, Connecticut, Japan, Norway, Tromsø, and Vaud. Conversely, the ORs for the studies in Los Angeles. Shanghai, southeastern Sweden, Uppsala, northern Sweden, northern Italy, and Athens were below one. The pattern of risk for salt water fish and shellfish was not substantially different from that of total fish. Fish was not associated with thyroid cancer risk in all studies combined (OR = 0.99, 95% CI 0.85-1.2 for moderate, and OR=0.88, 95% CI 0.71-1.1 for high total fish consumption), but there was a suggestion of a protective effect in endemic goiter areas (OR = 0.65, 95% CI 0.48-0.88). CONCLUSION: This combined analysis indicates that relatively elevated fish consumption does not appreciably increase thyroid cancer risk, and may have a favorable influence in areas where iodine deficiency is, or was, common.

Early gender differences in adolescent tobacco use--the experience of a Swedish cohort.

BACKGROUND: In Sweden, the prevalence of tobacco use in the youth population differs by product and gender, but there are no longitudinal studies of gender differences in the uptake of smoking and use of oral snuff (OS). METHODS: A prospective cohort study ongoing in the County of Stockholm, encompassing 3,019 children recruited in 1997 in the fifth grade of compulsory school, of whom 96% were followed-up in the sixth grade. RESULTS: At baseline, 22% of the boys and 15% of the girls had ever smoked, respectively 8% and 3% had ever used oral moist snuff. One year later, the overall smoking prevalence had markedly increased, as did the transition to more advanced stages of smoking, especially among girls. Among boys who at baseline had only used oral snuff, 41% had also smoked cigarettes at follow-up. Lack of a firm intention to abstain from tobacco use was strongly associated with onset of experimentation within one year, particularly among boys. CONCLUSIONS: Tobacco uptake in pre-adolescence differs between genders, with an earlier initiation among boys and a more rapid transition to regular smoking among girls. In most cases, experimentation with oral snuff among boys marks the transition to cigarette smoking.

Factors affecting reproducibility of dietary reports using food frequency questionnaires.

OBJECTIVE: To study the reproducibility of a food frequency questionnaire used to assess past dietary habits. DESIGN: Repeated retrospective assessment of dietary habits of a population sample. SETTING: Uppsala-Orebro Health Care Region of Sweden. SUBJECTS: One-hundred and four subjects participating as control subjects in a case-control study on thyroid cancer. INTERVENTIONS: Between spring 1993 and spring 1994 a case-control study was conducted in the study area, in order to investigate risk factors for thyroid cancer-diet among others. The study subjects reported their consumption of selected foods with reference 1-5 y before, as well as dietary changes that occurred from adolescence to adult age. One year later 197 control persons were invited to provide a second report of the same food items. Of the invited subjects 104 agreed to participate. RESULTS: The median Spearman rank correlation coefficient between the first and second assessment was 0.58 for food consumption and 0. 56 for nutrients intake. Correlation between the two assessments varied greatly between food items, ranging from -0.03 to 0.83. The correlation was positively related to the frequency and negatively related to the skewness of consumption. The recall of dietary changes from adolescence had a median correlation coefficient of 0. 38 (range 0.19-0.69). There were hints of a higher reproducibility of dietary reports among men and among highly educated subjects (more than 11 y of education), but these differences were statistically significant only for recall of adolescent diet. Reproducibility of nutrients intake was also significantly higher among men than among women, as well as among subjects older than 45 y. CONCLUSIONS: The reproducibility of dietary reports was satisfactory. Among factors affecting reproducibility, frequency and homogeneity of consumption in the source population are presumably the most important. Age, sex and education modify the inter-subject reproducibility of past diet. Based on reproducibility of a semi-quantitative index, the recall of adolescent diet probably has a low validity. European Journal of Clinical Nutrition (2000) 54, 658-664.

Diet-associated risks of disease and self-reported food consumption: how shall we treat partial nonresponse in a food frequency questionnaire?

Using data from a population-based case-control study on thyroid cancer, we studied two approaches of handling missing answers in a food frequency questionnaire when estimating food consumption and nutrient intakes. We analyzed the dietary reports of 165 cases and 248 control subjects. In the first approach, the omitted food items were considered as "null consumption." In the second approach, the missing answers were replaced with the median frequencies for subjects in the corresponding outcome category actually answering that specific food item. The results showed marginal differences between the two methods. In addition, the null consumption assumption was validated by means of complementary telephone interviews with a subsample of subjects who provided incomplete reports. Overall, the originally omitted answers actually corresponded to very rare consumption for 54.2% of cancer patients and for 54.7% of controls. However, this "true" proportion of null consumption varied greatly between different food items (range 0-96%) and between food groups (range 14-82%). To interpret the omitted self-reports of food consumption as indication of "zero consumption" is quite reasonable when the investigation does not focus on dietary items widely consumed in the source population.

A pooled analysis of thyroid cancer studies. V. Anthropometric factors.

OBJECTIVE: To assess the relation between anthropometric factors and thyroid cancer risk in a pooled analysis of individual data from 12 case-control studies conducted in the US, Japan, China and Europe. METHODS: 2056 female and 417 male cases, 3358 female and 965 male controls were considered. Odds ratios (OR) were derived from logistic regression, conditioning on age, A-bomb exposure (Japan) and study, and adjusting for radiotherapy. RESULTS: Compared to the lowest tertile of height, the pooled OR was 1.2 for females for the highest one, and 1.5 for males, and trends in risk were significant. With reference to weight at diagnosis, the OR for females was 1.2 for the highest tertile, and the trend in risk was significant, whereas no association was observed in males. Body mass index (BMI) at diagnosis was directly related to thyroid cancer risk in females (OR = 1.2 for the highest tertile), but not in males. No consistent pattern of risk emerged with BMI during the late teens. Most of the associations were observed both for papillary and follicular cancers, and in all age groups. However, significant heterogeneity was observed across studies. CONCLUSIONS: Height and weight at diagnosis are moderately related to thyroid cancer risk.

Incidence of thyroid cancer in Scandinavia following fallout from atomic bomb testing: an analysis of birth cohorts.

OBJECTIVES: The occurrence relation between radioactive fallout from nuclear testing at Novaja Semlja in north-west Russia and the incidence of thyroid cancer in Norway and Sweden was studied following a birth cohort approach. METHODS: Birth cohorts with presumably different levels of exposure were identified according to calendar year of atomic tests and previous Norwegian estimates of the population dose (born 1947-1950 received low exposure in late childhood, born 1951-1962 received the highest exposure in early childhood, born 1963-1970 were not exposed). For each one-year birth cohort the incidence rates were calculated, with denominators based on exact population figures for each year of follow-up. RESULTS: In a stratified analysis, the relative risk for the highest exposed cohorts born 1951-1962, compared to those not exposed born 1963-1970, was found to decrease with increasing age from a borderline significant relative risk (RR) of 1.7 (95 percent confidence interval, 95% CI: 1.0-3.0) for children in the age-group 7-14 years to no excess risk among those 20-24 years of age (RR: 0.9; 95% CI: 0.7-1.2). The mean age at diagnosis of thyroid cancer in the age-group 7 14 years was lowest in the birth cohorts with the highest exposure. The Poisson regression analysis showed essentially the same results, with an improved fit when adding an interaction term between age and birth-cohort to a basic model with age, gender, birth-cohort and country. CONCLUSION: These results are compatible with an increased risk of thyroid cancer during childhood and adolescence for subjects exposed to radioactive fallout early in life. Alternative explanations for the pattern of incidence are discussed.

A pooled analysis of case-control studies of thyroid cancer. I. Methods.

OBJECTIVE: Because the etiology of thyroid cancer is not well described, we conducted a pooled analysis of all published case-control studies, as well as two identified unpublished studies. This paper describes the major characteristics of the 14 studies included in the analysis, as well as the statistical methods employed. Four studies were conducted in the United States (1 each in Washington State, California, Connecticut and Hawaii), 8 in Europe (3 in Sweden, 2 in Norway, 1 in Switzerland, 1 in Italy and 1 in Greece), and 2 in Asia (1 in China and 1 in Japan). METHODS: The original datasets were obtained and restructured in a uniform format. Data on socio-demographic characteristics, anthropometric measures, smoking and alcohol consumption, history of benign thyroid diseases and of other selected medical conditions and treatments, family history of cancer and of benign thyroid conditions, occupation, residence in endemic goitre areas, and dietary habits were analyzed. For women, we also analyzed menstrual and reproductive factors and use of female hormones. Radiotherapy and, in Japan, exposure to the A-bombs were considered as potential confounding factors. RESULTS: A total of 2,725 cases (2,247 females and 478 males) and 4,776 controls (3,699 females and 1,077 males) were included in this study. Of the cases, 79% were classified as papillary thyroid carcinomas, 14% as follicular, 2% medullary, 1% anaplastic, 1% other histologies, and 3% histological type unknown. Each of the datasets was checked for outliers and consistency. Data were analysed separately by study center, gender, and the two major histologic types (papillary, follicular). Frequency tables and simple statistics were computed for each variable under study. Conditional logistic regression was used to compute odds ratios. For matched studies, the original matching was preserved, whereas, for unmatched ones, five-year age groups were used for matching. Study-specific analyses were computed, and then the data from all the studies were pooled conditioning on study. Heterogeneity between studies, geographic areas and study designs was assessed, and the modifying effect of age was also evaluated.