Maria Rosaria Galanti

A pooled analysis of case-control studies of thyroid cancer II. Menstrual and reproductive factors

Objective: It has been suggested that female hormones, and hence menstrual and reproductive factors, play a role in thyroid cancer etiology. Epidemiological data, however, are limited and inconsistent, partly because of the small number of cases included in each study. To clarify the etiology of thyroid cancer, we conducted a pooled analysis of original data from 14 case-control studies, 4 from the United States, 2 from Asia, and 8 from Europe.Methods: This analysis included a total of 2,247 female cases of thyroid cancer (80% papillary) and 3,699 control women. Pooled odds ratios (OR) were estimated using logistic regression, conditioning on study and (i) matching sets for individually matched studies, or (ii) quinquennia of age for the other studies. Additional terms for age and history of radiation exposure were included in the regression equations.Results: The OR per year of later menarche was 1.04 (95% confidence interval (CI) 1.0–1.1). Compared to pre-menopausal women, the OR was 1.3 for women with natural menopause, and 1.8 for those with artificial menopause, but the studies were heterogeneous and the association may be due, at least in part, to diagnostic or ascertainment bias. Parity, spontaneous or induced abortions and history of infertility were not associated with thyroid cancer risk. The OR was above unity in women reporting later age at first birth (OR=1.1, 95% CI 1.0–1.3 for 5-year delay) and higher in the first years after a birth.Conclusions: The associations of menstrual and reproductive factors with thyroid cancer risk were generally weak, but appeared stronger among women diagnosed with thyroid cancer at younger ages.

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.

The effectiveness of a school-based substance abuse prevention program: 18-month follow-up of the EU-Dap cluster randomized controlled trial

AIM To evaluate the effectiveness of a school-based substance abuse prevention program developed in the EU-Dap study (EUropean Drug Addiction Prevention trial). MATERIALS AND METHODS Cluster Randomized Controlled Trial. Seven European countries participated in the study; 170 schools (7079 pupils 12-14 years of age) were randomly assigned to one of three experimental conditions or to a control condition during the school year 2004/2005. The program consisted of a 12-h curriculum based on a comprehensive social influence approach. A pre-test survey assessing past and current substance use was conducted before the implementation of the program, while a post-test survey was carried out about 18 months after the pre-test. The association between program condition and change in substance use at post-test was expressed as adjusted prevalence odds ratio (POR), estimated by multilevel regression models. RESULTS Persisting beneficial program effects were found for episodes of drunkenness (any, POR=0.80; 0.67-0.97; frequent, POR=0.62; 0.47-0.81) and for frequent cannabis use in the past 30 days (POR=0.74; 0.53-1.00), whereas daily cigarette smoking was not affected by the program as it was at the short-term follow-up. Baseline non-smokers that participated in the program progressed in tobacco consumption to a lower extent than those in the control condition, but no difference was detected in the proportion of quitters or reducers among baseline daily smokers. CONCLUSION The experimental evaluation of an innovative school curriculum based on a comprehensive social influence approach, indicated persistent positive effects over 18 months for alcohol abuse and for cannabis use, but not for cigarette smoking.

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

AbstractObjective: 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.

A pooled analysis of case-control studies of thyroid cancer. III. Oral contraceptives, menopausal replacement therapy and other female hormones.

Objective: The relations between oral contraceptives (OC), hormone replacement therapy (HRT) for menopause, and other female hormone use and thyroid cancer risk was analyzed using the original data from 13 studies from North America, Asia and Europe.Methods: Based on 2,132 cases and 3,301 controls, odds ratios (OR) and the corresponding 95% confidence intervals (CI) were obtained by conditional regression models, conditioning on study and age at diagnosis, and adjusting for age, radiation exposure and parity.Results: Overall, 808 (38%) cases versus 1,290 (39%) controls had ever used OCs, corresponding to an OR of 1.2 (95% CI 1.0 to 1.4). There was no relation with duration of use, age at first use, or use before first birth. The OR was significantly increased for current OC users (OR=1.5, 95% 1.0 to 2.1), but declined with increasing time since stopping (OR=1.1 for >10 years since stopping). The association was stronger for papillary cancers (OR=1.6 for current users) than for other histologic types. No significant heterogeneity was observed across studies or geographic areas. Eight studies had data on HRT, for a total of 1,305 cases and 2,300 controls: 110 (8%) cases and 205 (9%) controls reported ever using HRT (OR=0.8; 95% CI 0.6 to 1.1). The ORs were 1.6 (95% to 0.9 to 2.9) for use of fertility drugs, and 1.5 (95% CI 1.1 to 2.1) for lactation suppression treatment.Conclusions: The studies considered in these analyses include most of the epidemiological data on the role of exogenous hormone use in the etiology of thyroid cancer, and they provide reassuring evidence on the absence of an association of practical relevance. The moderate excess risk in current OC users, if not due to increased surveillance for thyroid masses among OC users, is similar to that described for breast cancer, and would imply a role of female hormones on thyroid cancer promotion. There was no indication of increased thyroid cancer risk 10 or more years after discontinuing OC use.

Long term mortality after severe starvation during the siege of Leningrad: prospective cohort study

Abstract Objectives To determine whether starvation during periods of increased growth after birth have long term health consequences. Design Analysis of cardiovascular risk factors and mortality in a longitudinal follow up after the 1941-4 siege of Leningrad. Mortality measured from 1975 up to the end of 1999. Setting St Petersburg, Russia (formerly Leningrad). Participants 5000 men born 1916-35 who lived in Leningrad, randomly selected to take part in health examinations in 1975-7. Of the 3905 men who participated, a third had experienced the siege. Main outcome measures Relative risk of ischaemic heart disease and mortality from stroke by siege exposure. Odds ratios and means for several cardiovascular risk factors. Results Three to six decades after the siege, in men who experienced the siege around the age of puberty blood pressure was raised (mean difference in systolic 3.3 mm Hg, in diastolic 1.3 mm Hg) as was mortality from ischaemic heart disease (relative risk 1.39, 95% confidence interval 1.07 to 1.79) and stroke (1.67, 1.15 to 2.43), including haemorrhagic stroke (1.71, 0.90 to 3.22). The effect on mortality was partly mediated via blood pressure but not by any other measured biological, behavioural, or social factor. Conclusions Starvation, or accompanying chronic stress, particularly at the onset of or during puberty, may increase vulnerability to later cardiovascular disease.

The effectiveness of a school-based substance abuse prevention program: EU-Dap cluster randomised controlled trial

OBJECTIVE To evaluate the effectiveness of the school-based drug abuse prevention program developed in the EU-Dap study (EUropean Drug Abuse Prevention trial) in preventing the use of tobacco, alcohol and drugs at the post-test. METHODS Cluster Randomised Controlled Trial. Seven European countries participated in the study; 170 schools (7079 pupils 12-14 years of age) were randomly assigned to one of three experimental conditions or to a control condition during the school year 2004/2005. A pre-test survey assessing past and current substance use was conducted before the implementation of the program. The program consisted in 12-hour class-based curriculum based on a comprehensive social-influence approach. A post-test survey was carried out in all participating schools, 3 months after the end of the program. The association between program condition and change in substance use at post-test was expressed as adjusted Prevalence Odds Ratio (POR), estimated by multilevel regression model. RESULTS Program effects were found for daily cigarette smoking (POR=0.70; 0.52-0.94) and episodes of drunkenness in the past 30 days (POR=0.72; 0.58-0.90 for at least one episode, POR=0.69; 0.48-0.99 for three or more episodes), while effects on Cannabis use in the past 30 days were of marginal statistical significance (POR=0.77; 0.60-1.00). The curriculum was successful in preventing baseline non-smokers or sporadic smokers from moving onto daily smoking, but it was not effective in helping baseline daily smokers to reduce or stop smoking. CONCLUSION School curricula based on a comprehensive social-influence model may delay progression to daily smoking and episodes of drunkenness.

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.

Symptoms of nicotine dependence in a cohort of Swedish youths: a comparison between smokers, smokeless tobacco users and dual tobacco users

AIMS To determine whether symptoms of nicotine dependence, addiction and withdrawal symptoms differ between exclusive smokers, exclusive snus (moist snuff) users and dual users. DESIGN A cross-sectional survey of a cohort subsample. Setting County of Stockholm, Sweden. PARTICIPANTS Current exclusive smokers (n = 466), exclusive snus users (n = 209) and dual users (n = 144), mean age 17.6 years. MEASUREMENTS Self-reported life-time experience of nicotine dependence and withdrawal symptoms in periods of discontinued tobacco use. Selected items from the modified Fagerstöm Tolerance Questionnaire (mFTQ), the Hooked on Nicotine Checklist (HONC) and the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). FINDINGS The odds ratio of endorsing each of four mFTQ items as well as the HONC item investigating the risk of feeling addicted to tobacco was two to five-fold higher for exclusive snus users and for dual users compared to exclusive smokers. One DSM-IV item (difficult to refrain from use) was elevated among dual users compared to smokers. Dual users reported the highest prevalence of any withdrawal symptom in contrast to exclusive snus users, who reported a lower risk of withdrawal symptoms compared to exclusive smokers. CONCLUSIONS Smokeless tobacco users show symptoms of nicotine dependence at least as frequently as cigarette smokers. Symptoms of nicotine dependence and of withdrawal during quit attempts are particularly frequent in the subgroup of users who combine smokeless tobacco with smoking.

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.