Ascertaining asthma status in epidemiologic studies: a comparison between administrative health data and self-report.

BACKGROUND: Studies have suggested that agreement between administrative health data and self-report for asthma status ranges from fair to good, but few studies benefited from administrative health data over a long period. We aimed to (1) evaluate agreement between asthma status ascertained in administrative health data covering a period of 30 years and from self-report, and (2) identify determinants of agreement between the two sources. METHODS: We used administrative health data (1983-2012) from the Quebec Birth Cohort on Immunity and Health, which included 81,496 individuals born in the province of Quebec, Canada, in 1974. Additional information, including self-reported asthma, was collected by telephone interview with 1643 participants in 2012. By design, half of them had childhood asthma based on health services utilization. Results were weighted according to the inverse of the sampling probabilities. Five algorithms were applied to administrative health data (having ≥ 2 physician claims over a 1-, 2-, 3-, 5-, or 30-year interval or ≥ 1 hospitalization), to enable comparisons with previous studies. We estimated the proportion of overall agreement and Kappa, between asthma status derived from algorithms and self-reports. We used logistic regression to identify factors associated with agreement. RESULTS: Applying the five algorithms, the prevalence of asthma ranged from 49 to 55% among the 1643 participants. At interview (mean age = 37 years), 49% and 47% of participants respectively reported ever having asthma and asthma diagnosed by a physician. Proportions of agreement between administrative health data and self-report ranged from 88 to 91%, with Kappas ranging from 0.57 (95% CI: 0.52-0.63) to 0.67 (95% CI: 0.62-0.72); the highest values were obtained with the [≥ 2 physician claims over a 30-year interval or ≥ 1 hospitalization] algorithm. Having sought health services for allergic diseases other than asthma was related to lower agreement (Odds ratio = 0.41; 95% CI: 0.25-0.65 comparing ≥ 1 health services to none). CONCLUSIONS: These findings indicate good agreement between asthma status defined from administrative health data and self-report. Agreement was higher than previously observed, which may be due to the 30-year lookback window in administrative data. Our findings support using both administrative health data and self-report in population-based epidemiological studies.

Bacillus Calmette-Guerin vaccination and multiple sclerosis: A population-based birth cohort study in Quebec, Canada.

BACKGROUND AND PURPOSE: The bacillus Calmette-Guerin (BCG) vaccine could reduce the incidence of multiple sclerosis (MS) through immunomodulation. Previous studies, presenting some limitations, reported no association. We re-examined this association in a large cohort focusing on relapsing-remitting MS (RRMS). METHODS: The cohort included 400,563 individuals, and was linked with the Quebec provincial BCG vaccination registry and administrative health data. Individuals were followed up from 1983 to 2014 and then within Period 1 (1983-1996) and Period 2 (1997-2014), for the occurrence of MS. Incident MS cases were defined as those with ≥3 hospital or physician claims for MS. Subjects with ≥1 drug reimbursement for MS disease-modifying therapies were classified as RRMS. Cox proportional hazards regression was used to estimate hazard ratios (HRs) over the follow-ups, adjusting for potential confounders. Possible effect modification due to sex was assessed. RESULTS: A total of 178,335 (46%) individuals were BCG vaccinated. There were 274 (0.06%) incident MS cases identified in 1983-1996, and 1433 (0.4%) in 1997-2014. No association was found with RRMS, either in Period 1 (adjusted HR [HRadj ] = 0.96, 95% confidence interval [CI] = 0.63-1.45; 96 cases) or in Period 2 (HRadj  = 1.02, 95% CI = 0.85-1.23; 480 cases). The remaining MS cases, for whom the phenotype was unknown, were positively associated with BCG over the entire follow-up (HRadj  = 1.25, 95% CI = 1.10-1.41; 1131 cases) and in Period 2 (HRadj  = 1.33, 95% CI = 1.17-1.52; 953 cases). No interaction with sex was found. CONCLUSIONS: Findings suggest that BCG vaccination does not decrease the risk of RRMS, and that future studies should consider phenotypes of MS.

Association between Bacillus Calmette-Guerin vaccination and type 1 diabetes in adolescence: A population-based birth cohort study in Quebec, Canada.

The Bacillus Calmette-Guerin (BCG) vaccine could reduce the incidence of type 1 diabetes through non-specific immunomodulation. Previous epidemiological studies, presenting some limitations, report no association. We examined this association of early life BCG vaccination and age at vaccination with type 1 diabetes incidence in adolescence in a large representative cohort in Quebec. The cohort included 387,704 individuals born in Quebec between 1970 and 1974 whose BCG vaccination status was determined from a provincial registry. Individuals were followed up from 1985 to their 19th birthday (maximum to 1993) for their use of physician services. Individuals were defined as type 1 diabetes cases if they had ≥4 related physician claims over a 2-year period, with at least 30 days between two claims. Cox proportional hazards regression was used to estimate the association of BCG vaccination and age at vaccination with type 1 diabetes. Covariates were selected based on a directed acyclic graph. Interaction according to sex was evaluated. A total of 178,133 (45.9%) individuals were vaccinated and 442 (0.11%) incident cases of type 1 diabetes were identified. The risk of type 1 diabetes was similar in vaccinated compared with unvaccinated individuals (adjusted hazard ratio = 1.06 [95% CI: 0.88-1.29]). There was no association with age at vaccination, and results did not differ by sex (Interaction, p = 0.60). Our results suggest that BCG vaccination does not prevent type 1 diabetes in adolescence.

Does group-based trajectory modeling estimate spurious trajectories?

BACKGROUND: Group-based trajectory modelling (GBTM) is increasingly used to identify subgroups of individuals with similar patterns. In this paper, we use simulated and real-life data to illustrate that GBTM is susceptible to generating spurious findings in some circumstances. METHODS: Six plausible scenarios, two of which mimicked published analyses, were simulated. Models with 1 to 10 trajectory subgroups were estimated and the model that minimized the Bayes criterion was selected. For each scenario, we assessed whether the method identified the correct number of trajectories, the correct shapes of the trajectories, and the mean number of participants of each trajectory subgroup. The performance of the average posterior probabilities, relative entropy and mismatch criteria to assess classification adequacy were compared. RESULTS: Among the six scenarios, the correct number of trajectories was identified in two, the correct shapes in four and the mean number of participants of each trajectory subgroup in only one. Relative entropy and mismatch outperformed the average posterior probability in detecting spurious trajectories. CONCLUSION: Researchers should be aware that GBTM can generate spurious findings, especially when the average posterior probability is used as the sole criterion to evaluate model fit. Several model adequacy criteria should be used to assess classification adequacy.

Classification and visualization of longitudinal patterns of medication dose: An application to interferon-beta-1a and amitriptyline in patients with multiple sclerosis.

PURPOSE: Describing patterns of use, including changes in dose and interruptions is challenging. Group-based trajectory modelling (GBTM) can be used to identify individuals with similar dose patterns. We provide an intuitive graphical representation of dose patterns in groups identified using GBTM. We illustrate our approach using two drugs with different combinations of available dosages. METHODS: We drew data on patients with MS followed from 1977 to 2014 in Montréal using two sub-cohorts of subjects. A sub-cohort of patients taking interferon-beta-1a and another of patients taking amitriptyline were identified from the initial cohort. We use GBTM to identify groups of patients with homogeneous dose patterns for each of the two drugs. We compared the graphical representation obtained from the fitted values of GBTM with our proposed approach, which consisted of using step functions whose values corresponded to the mode. Differences in characteristics across groups were identified using chi-squares and analysis of variance, both weighted by the posterior probability of group membership. RESULTS: Seven patterns of dose were identified for interferon-beta-1a and five for amitriptyline. The graphical representations of the patterns of dose from GBTM included values outside of the prescribed doses and did not capture changes in dose as clearly as the proposed representation using step functions. CONCLUSION: Our proposed approach which is based on the mode at each visit in each pattern provides an intuitive and realistic representation of dose patterns in groups identified with GBTM.

HIV Modifies the Effect of Tobacco Smoking on Oral Human Papillomavirus Infection.

BACKGROUND: People living with HIV (PLWH) are more likely to smoke and harbor oral human papillomavirus (HPV) infections, putting them at higher risk for head and neck cancer. We investigated effects of HIV and smoking on oral HPV risk. METHODS: Consecutive PLWH (n = 169) and at-risk HIV-negative individuals (n = 126) were recruited from 2 US health centers. Smoking history was collected using questionnaires. Participants provided oral rinse samples for HPV genotyping. We used multivariable logistic regression models with interaction terms for HIV to test for smoking effect on oral HPV. RESULTS: PLWH were more likely to harbor oral HPV than HIV-negative individuals, including α (39% vs 28%), ß (73% vs 63%), and γ-types (33% vs 20%). HIV infection positively modified the association between smoking and high-risk oral HPV: odds ratios for smoking 3.46 (95% confidence interval [CI], 1.01-11.94) and 1.59 (95% CI, .32-8.73) among PLWH and HIV-negative individuals, respectively, and relative excess risk due to interaction (RERI) 3.34 (95% CI, -1.51 to 8.18). RERI for HPV 16 was 1.79 (95% CI, -2.57 to 6.16) and 2.78 for ß1-HPV (95% CI, -.08 to 5.65). CONCLUSION: Results show tobacco smoking as a risk factor for oral HPV among PLWH.

Latency of tobacco smoking for head and neck cancer among HPV-positive and HPV-negative individuals.

Human papillomavirus (HPV) infection and tobacco smoking are well-known risk factors for head and neck cancers (HNC). Although an effect modification between oral HPV infection and tobacco smoking may exist, evidence is lacking on how they interact temporally. We investigated the latency and life course effects of tobacco smoking on risk of HNC among HPV-positive (HPV+ve ) and negative (HPV-ve ) individuals. We used data from 631 ever-smoker participants of a hospital-based case-control study conducted in four major hospitals in Montréal, Canada. Cases (n = 320), incident, histologically confirmed, primary squamous cell carcinomas, were frequency-matched to controls (n = 311) by age and sex. Sociodemographic and behavioral factors (e.g., tobacco and alcohol use and sexual history) were collected using a structured interview applying a life grid technique. Oral exfoliated cells were used for HPV DNA detection and genotyping. Latency effects were estimated flexibly using a Bayesian relevant exposure model and further extended with a life course approach. Retrospective smoking trajectories for HPV+ve cases and controls had similar shapes. Exposure to tobacco smoking even 40 years before diagnosis was associated with an increased HNC risk among both HPV+ve and HPV-ve participants. The effect of smoking before the start of sexual activity compared to afterwards was higher among HPV+ve individuals. This pattern of association was less profound among HPV-ve participants. Temporal interactions may exists between oral HPV infection and life course smoking trajectories in relation to HNC risk.

Shared social mechanisms underlying the risk of nine cancers: A life course study.

Identifying life periods during which social conditions have the highest impact on risk of common cancers in a population may help to reveal their underlying shared social mechanisms. We used the life course framework to estimate the extent to which life course SEP is associated with risk of nine cancers. In addition, we tested whether these associations conform to a critical period or cumulative life course model. Data were from a population-based case-control study of occupational exposures and cancer conducted in Montreal, Canada. Participants were males aged 35-70 years (n = 2,547) residing in the Montreal metropolitan area with primary, histologically confirmed cancers diagnosed between 1979 and 1985. Population controls (n = 512) were sampled from electoral lists. SEP was measured at three different periods of life based on respondent's report: during childhood, young adulthood and mid-life. We used a structured modeling approach using a series of unconditional logistic regressions to test which models best fit the data. Life course SEP increased the risk of all cancers. SEP in childhood was identified as a critical period for prostate and all gastrointestinal tract cancers except for esophagus cancer. In addition, the accumulation model best explained the data for melanoma and lung squamous cell carcinoma. Our findings suggest that childhood social circumstances are a common risk factor for several cancers among men; our results provide insights into the mechanisms involved in the etiology of nine cancers.

Asthma phenotypes based on health services use for allergic diseases in a province-wide birth cohort.

BACKGROUND: Many previous studies on asthma phenotypes were conducted in selected clinical populations and overlooked changes throughout the life course. OBJECTIVE: To identify asthma phenotypes based on use of health services for allergic diseases in 3 life periods and document transitions among phenotypes across life periods. METHODS: In a population-based cohort of 78,211 individuals born in 1974 in the province of Québec, Canada, we documented medical visits and hospitalizations for asthma and other allergic diseases until 1994. Phenotypes based on clusters of health services use in childhood (8-12 years of age), adolescence (13-17 years of age), and young adulthood (18-20 years of age) were identified using a hierarchical method among 9,989 individuals (12.8%) who had at least one health encounter for asthma during follow-up. Population-level probabilities of transitioning among phenotypes were estimated in the full study population. RESULTS: In the subset with asthma, 6 phenotypes were identified during both childhood and young adulthood and 7 during adolescence. The most common phenotype was no asthma or allergic diseases: 58% in childhood, 42% in adolescence, and 54% in adulthood. The second most common was the mild asthma and no allergic diseases phenotype, representing 36%, 31%, and 21%, respectively, in these 3 periods. In the study population, 87% of the individuals remained in the no asthma phenotype group during the follow-up. Most individuals in the asthma phenotypes transitioned over time. CONCLUSION: Our study uniquely contributes to a better understanding, at the population level, of the manifestations and transitions in asthma phenotypes during the life course.

Occupational exposures to leaded and unleaded gasoline engine emissions and lung cancer risk.

OBJECTIVES: To determine whether occupational exposure to gasoline engine emissions (GEE) increased the risk of lung cancer and more specifically whether leaded or unleaded GEE increased the risk. METHODS: Two population-based case-control studies were conducted in Montreal, Canada. The first was conducted in the early 1980s and included many types of cancer including lung cancer. The second was conducted in the late 1990s and focused on lung cancer. Population controls were used in both studies. Altogether, there were 1595 cases and 1432 population controls. A comprehensive expert-based exposure assessment procedure was implemented and exposure was assessed for 294 agents, including unleaded GEE, leaded GEE and diesel engine emissions (DEE). Logistic regression analyses were conducted to estimate ORs between various metrics of GEE exposure and lung cancer, adjusting for smoking, DEE and other potential confounders. RESULTS: About half of all controls were occupationally exposed to GEE. Irrespective of the metrics of exposure (any exposure, duration of exposure and cumulative exposure) and the type of lung cancer, and the covariates included in models, none of the point estimates of the ORs between occupational exposure to leaded or unleaded GEE and lung cancer were above 1.0. Pooling two studies, the OR for any exposure to leaded GEE was 0.82 (0.68-1.00). CONCLUSIONS: Our results do not support the hypothesis that occupational exposure to GEE increases the risk of lung cancer.

Aetiological heterogeneity of head and neck squamous cell carcinomas: the role of human papillomavirus infections, smoking and alcohol.

Tobacco and alcohol consumption are the main risk factors for head and neck squamous cell carcinoma (HNSCC). In addition, human papillomavirus (HPV) infection plays a causal role in oropharyngeal cancer (OPC), a subset of HNSCC. We assessed the independent effects of tobacco, alcohol and HPV infection on OPC risk in the head and neck cancer (HeNCe) Life study, a hospital-based case-control study of HNSCC with frequency-matched controls by age and sex from four Montreal hospitals. Interviewers collected information on socio-demographic and behavioural factors. We tested exfoliated oral cells for HPV DNA by polymerase chain reaction (PCR). We included only OPC cases (n = 188) and controls (n = 427) without missing values for HPV, smoking or alcohol. We examined associations by estimating odds ratios (ORs) and corresponding 95% confidence intervals (CI) using unconditional logistic regression. Smoking (OR = 1.90, 95% CI: 1.04-3.45) and alcohol (OR = 2.74, 95% CI: 1.45-5.15) were associated with an increased risk of OPC independent of HPV status. Positivity for HPV 16 among heavy smokers and heavy alcohol users was associated with a 30.4-fold (95% CI: 8.94-103.26) and 18.6-fold (95% CI: 5.75-60.13) elevation in risk of OPC relative to participants who were HPV negative, respectively. Moreover, the combined effect of heavy smoking and alcohol comsumption with HPV 16 infection substantially increased OPC risk (OR = 48.76, 95% CI: 15.83-150.17) and (OR = 50.60, 95% CI: 15.96-160.40), respectively. Our results support the independent roles of smoking, alcohol and HPV infection in OPC risk and a possible combined effect. Efforts should be made to tackle these major risk factors simultaneously.

Association Between Bacillus Calmette-Guérin Vaccination and Childhood Asthma in the Quebec Birth Cohort on Immunity and Health.

We estimated the association between bacillus Calmette-Guérin (BCG) vaccination and childhood asthma in a birth cohort using administrative databases, and we determined the impact of adjusting for potential confounders collected from a subset of the cohort members. Data were collected in 2 waves: 1) Administrative data for 76,623 individuals (stage 1) was gathered from the Quebec Birth Cohort on Immunity and Health (1974-1994), including BCG vaccination status, perinatal and sociodemographic characteristics, and use of health services for asthma; and 2) self-reported asthma risk factors were collected in 2012 by telephone interviews with 1,643 participants (stage 2) using a balanced 2-stage sampling design. We estimated odds ratios and 95% confidence intervals for asthma using logistic regression and correcting for the known sampling fractions from stage 1 to stage 2, overall and sex-stratified. In total, 35,612 (46.5%) individuals were BCG vaccinated, and 5,870 (7.7%) had asthma. The final odds ratio, integrating results from both stages of sampling, was 0.95 (95% confidence interval: 0.87, 1.04). Results did not differ according to sex (P for interaction = 0.327). To our knowledge, this is the largest study ever conducted on this topic, and using the best possible comprehensive adjustment for confounders, we found no association between BCG vaccination and asthma.

Lifetime report of perceived stress at work and cancer among men: A case-control study in Montreal, Canada.

BACKGROUND: The association between perceived workplace psychological stress, over the entire work career, and cancer among men has never been assessed. This was explored in the context of a population-based case-control study conducted in Montreal, Canada. METHODS: 3103 incident cancer cases (11 types) diagnosed in 1979-1985 and 512 population controls were interviewed. Subjects described in detail each job held during their lifetime, including the occurrence of stress, and its reason. Logistic regression estimated odds ratios (OR) and 95% confidence intervals (CI) for the association between perceived workplace stress and its duration, and each cancer site, adjusting for lifestyle and occupational factors. RESULTS: Employment in at least one stressful job was associated with increased odds of cancers of the lung (OR=1.33, 95% CI: 1.01-1.75), colon (OR=1.51, 95% CI: 1.15-1.98), bladder (OR=1.37, 95% CI: 1.03-1.81), rectal (OR=1.52, 95% CI: 1.10-2.10), and stomach (OR=1.53, 95% CI: 1.08-2.15). A duration-response trend was found for cancers of the lung, colon, rectum, stomach, and for NHL. Subjects reported changes in stress level over their career. Perceived stress was ascribed to several sources, including high demand and time pressure, financial issues, job insecurity, and hazardous conditions. CONCLUSION: Prolonged exposure to perceived stress at work was associated with greater odds of cancer at 5 out of 11 sites. While over reporting of stress by cases cannot be fully ruled out, these associations, if substantiated, would bear important public health significance. Prospective studies building on detailed stress assessment protocols considering all sources and changes over the career are necessary.

Investigating Socioeconomic Position in Dental Caries and Traumatic Dental Injury among Children in Quebec.

OBJECTIVES: Socioeconomic position (SEP) is inversely associated with most oral health outcomes, but the patterns of association may vary depending on the specific outcome. We estimated associations between SEP and two oral health outcomes, dental caries and traumatic dental injuries (TDI), in Quebec children. METHODS: We used data from the baseline visit of the QUALITY (QUebec Adipose and Lifestyle Investigation in Youth) Cohort, an ongoing study in Montreal and Quebec, Canada. The analytical sample included 590 children aged 8-10 years. Data on parents' SEP (household income, education) and children's health behaviours and involvement in sports were obtained through questionnaires and interviews. Oral health outcomes (dental caries and TDI in permanent teeth) were assessed by clinical oral exam. Negative binomial regression was used to model dental caries (DMFS index) and number of teeth with TDI adjusting for selected covariates. RESULTS: The mean (SD) DMFS and number of TDI were 0.61 (1.43) and 0.12 (0.43), respectively. Compared to the upper quartile of income, children in the lower quartile had a DMFS approximately 3 times higher (PRR=2.68, 95% CI: 1.43, 5.04). Adjusting for oral health and nutritional behaviours had no effect. Conversely, children in the highest income quartile had a 3 times higher number of teeth with TDI compared to the lowest quartile (PRR=3.14, 95% CI: 1.22, 8.08). Physical activity did not explain this relationship. Parents' education was not associated with dental caries or TDI. CONCLUSION: SEP seems to play a different role in the cause of dental caries and TDI.

No role for human papillomavirus infection in oral cancers in a region in southern India.

Oral cancer is a major public health issue in India with ∼ 77,000 new cases and 52,000 deaths yearly. Paan chewing, tobacco and alcohol use are strong risk factors for this cancer in India. Human papillomaviruses (HPVs) are also related to a subset of head and neck cancers (HNCs). We examined the association between oral HPV and oral cancer in a sample of Indian subjects participating in a hospital-based case-control study. We recruited incident oral cancer cases (N = 350) and controls frequency-matched by age and sex (N = 371) from two main referral hospitals in Kerala, South India. Sociodemographic and behavioral data were collected by interviews. Epithelial cells were sampled using Oral CDx® brushes from the oral cancer site and the normal mucosa. Detection and genotyping of 36 HPV genotypes were done using a polymerase chain reaction protocol. Data collection procedures were performed by qualified dentists via a detailed protocol with strict quality control, including independent HPV testing in India and Canada. HPV DNA was detected in none of the cases or controls. Associations between oral cancer and risk factors usually associated with HPV infection, such as oral sex and number of lifetime sexual partners, were examined by logistic regression and were not associated with oral cancer. Lack of a role for HPV infection in this study may reflect cultural or religious characteristics specific to this region in India that are not conducive to oral HPV transmission. A nationwide representative prevalence study is needed to investigate HPV prevalence variability among Indian regions.

Periodontal diseases and risk of oral cancer in Southern India: Results from the HeNCe Life study.

Some studies suggest that periodontal diseases increase the risk of oral cancer, but contradictory results also exist. Inadequate control of confounders, including life course exposures, may have influenced prior findings. We estimate the extent to which high levels of periodontal diseases, measured by gingival inflammation and recession, are associated with oral cancer risk using a comprehensive subset of potential confounders and applying a stringent adjustment approach. In a hospital-based case-control study, incident oral cancer cases (N = 350) were recruited from two major referral hospitals in Kerala, South India, from 2008 to 2012. Controls (N = 371), frequency-matched by age and sex, were recruited from clinics at the same hospitals. Structured interviews collected information on several domains of exposure via a detailed life course questionnaire. Periodontal diseases, as measured by gingival inflammation and gingival recession, were evaluated visually by qualified dentists following a detailed protocol. The relationship between periodontal diseases and oral cancer risk was assessed by unconditional logistic regression using a stringent empirical selection of potential confounders corresponding to a 1% change-in-estimates. Generalized gingival recession was significantly associated with oral cancer risk (Odds Ratio = 1.83, 95% Confidence Interval: 1.10-3.04). No significant association was observed between gingival inflammation and oral cancer. Our findings support the hypothesis that high levels of periodontal diseases increase the risk of oral cancer.

Evaluating the Validity of a Two-stage Sample in a Birth Cohort Established from Administrative Databases.

BACKGROUND: When using administrative databases for epidemiologic research, a subsample of subjects can be interviewed, eliciting information on undocumented confounders. This article presents a thorough investigation of the validity of a two-stage sample encompassing an assessment of nonparticipation and quantification of the extent of bias. METHODS: Established through record linkage of administrative databases, the Québec Birth Cohort on Immunity and Health (n = 81,496) aims to study the association between Bacillus Calmette-Guérin vaccination and asthma. Among 76,623 subjects classified in four Bacillus Calmette-Guérin-asthma strata, a two-stage sampling strategy with a balanced design was used to randomly select individuals for interviews. We compared stratum-specific sociodemographic characteristics and healthcare utilization of stage 2 participants (n = 1,643) with those of eligible nonparticipants (n = 74,980) and nonrespondents (n = 3,157). We used logistic regression to determine whether participation varied across strata according to these characteristics. The effect of nonparticipation was described by the relative odds ratio (ROR = ORparticipants/ORsource population) for the association between sociodemographic characteristics and asthma. RESULTS: Parental age at childbirth, area of residence, family income, and healthcare utilization were comparable between groups. Participants were slightly more likely to be women and have a mother born in Québec. Participation did not vary across strata by sex, parental birthplace, or material and social deprivation. Estimates were not biased by nonparticipation; most RORs were below one and bias never exceeded 20%. CONCLUSIONS: Our analyses evaluate and provide a detailed demonstration of the validity of a two-stage sample for researchers assembling similar research infrastructures.

Bacillus Calmette-Guérin (BCG) Vaccination in Infancy and Risk of Childhood Diabetes.

BACKGROUND: A narrow time window in infancy may be relevant for the aetiology of immune-mediated type 1 diabetes. We investigated whether a non-specific immune stimulation in the first year of life, as resulting from Bacillus Calmette-Guérin (BCG) vaccination, was associated with childhood diabetes. METHODS: Using data from a birth cohort assembled through linkage of administrative databases, 78,492 subjects born in 1974 were the object of the present analysis. Information was extracted from the birth, death, and BCG vaccination registries. Diabetes-related health services were obtained from administrative health databases (physician billing claims and hospitalisation data) until 1994. Subjects were classified as having diabetes according to two validated definitions: (1) ≥2 diabetes-related medical visits within 2 years or ≥1 hospitalisation for diabetes; and 2) ≥4 diabetes-related medical visits within 2 years. Cox proportional hazards regression was used to estimate adjusted hazard ratios (HR) and 95% confidence interval (CI), adjusted for potential confounders. RESULTS: Forty-four per cent of subjects were BCG vaccinated in the first year of life. According to the first and second definition, respectively, 293 (0.37%) and 230 (0.29%) subjects were classified as having diabetes. There was no association between BCG vaccination in the first year of life and risk of diabetes with either definition (HR(def1) = 0.92, 95% CI 0.73, 1.17; HR(def2) = 1.04, 95% CI 0.80, 1.37), and results did not differ by sex. CONCLUSIONS: Given the potentially critical importance of the exposure window and paucity of studies addressing BCG vaccination timing in relation to diabetes risk, this question deserves further investigation.

Lack of a protective effect of cotton dust on risk of lung cancer: evidence from two population-based case-control studies.

BACKGROUND: Lung cancer is the leading cause of cancer death in North America. Exposure to cotton dust has previously been reported to decrease the risk of lung cancer. METHODS: We used data from two large case-control studies conducted in Montreal from 1979-1986 (Study 1) and 1996-2002 (Study 2) respectively, to examine the association between occupational exposure to cotton dust and risk of lung cancer. Cases were diagnosed with incident histologically-confirmed lung cancer (857 in Study 1, 1203 in Study 2). Population controls were randomly selected from electoral lists and frequency-matched to cases by age and sex (533 in Study 1, 1513 in Study 2). Interviews for the two studies used a virtually identical questionnaire to obtain lifetime occupational and smoking history, and several lifestyle covariates. Each participant's lifetime occupational history was reviewed by experts to assess exposure to a number of occupational agents, including cotton dust. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by unconditional logistic regression, adjusting for potential confounders. RESULTS: The lifetime prevalence of exposure to cotton dust was approximately 10%-15% in both studies combined, with some variation by study and by sex. Overall there was no decreased risk of lung cancer among subjects exposed to cotton dust. Rather, among all subjects there was a suggestion of slightly increased risk associated with any lifetime exposure to cotton dust (OR = 1.2, 95% CI: 1.0-1.5). This risk appeared to be concentrated among cases of adenocarcinoma (OR = 1.6, 95% CI: 1.2-2.2), and among moderate and heavy smokers (OR = 1.3, 95% CI: 1.0-1.7). There was no association when restricting to cases of either squamous cell or small cell cancer, or among never smokers and light smokers. An analogous examination of subjects exposed to wool dust revealed neither increased nor decreased risks of lung cancer. CONCLUSIONS: There was no evidence that cotton dust exposure decreased risks of lung cancer.

Circumcision and prostate cancer: a population-based case-control study in Montréal, Canada.

OBJECTIVES: To investigate the possible association between circumcision and prostate cancer risk, to examine whether age at circumcision influences prostate cancer risk, and to determine whether race modifies the circumcision-prostate cancer relationship. SUBJECTS AND METHODS: PROtEuS (Prostate Cancer and Environment Study), a population-based case-control study set amongst the mainly French-speaking population in Montréal, Canada, was used to address study objectives. The study included 1590 pathologically confirmed prostate cancer cases diagnosed in a Montréal French hospital between 2005 and 2009, and 1618 population controls ascertained from the French electoral list, frequency-matched to cases by age. In-person interviews elicited information on sociodemographic, lifestyle and environmental factors. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) between circumcision, age at circumcision and prostate cancer risk, adjusting for age, ancestry, family history of prostate cancer, prostate cancer screening history, education, and history of sexually transmitted infections. RESULTS: Circumcised men had a slightly lower risk, albeit not statistically significant, of developing prostate cancer than uncircumcised men (OR 0.89, 95% CI 0.76-1.04). Circumcision was found to be protective in men circumcised aged ≥36 years (OR 0.55, 95% CI 0.30-0.98). A weaker protective effect was seen among men circumcised within 1 year of birth (OR 0.86, 95% CI 0.72-1.04). The strongest protective effect of circumcision was recorded in Black men (OR 0.40, 95% CI 0.19-0.86, P-value for interaction 0.02) but no association was found with other ancestral groups. CONCLUSION: Our findings provide novel evidence for a protective effect of circumcision against prostate cancer development, especially in those circumcised aged ≥36 years; although circumcision before the age of 1 year may also confer protection. Circumcision appeared to be protective only among Black men, a group that has the highest rate of disease. Further research into the differences in effect of circumcision on prostate cancer risk by ancestry is warranted, as is the influence of age at circumcision.