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Abstract Background Few epidemiologic findings are as well established as the association between smoking and lung cancer. It is therefore somewhat surprising that there is not yet a clear consensus about the exposure-response relationships between various metrics of smoking and lung cancer risk. In part this is due to heterogeneity of how exposure-response results have been presented and the relative paucity of published results using any particular metric of exposure. The purposes of this study are: to provide new data on smoking-lung cancer associations and to explore the relative impact of different dimensions of smoking history on lung cancer risk. Methods Based on a large lung cancer case-control study (1203 cases and 1513 controls) conducted in Montreal in 1996–2000, we estimated the lifetime prevalence of smoking and odds ratios in relation to several smoking metrics, both categorical and continuous based on multivariable unconditional logistic regression. Results Odds ratios (ORs) for ever vs never smoking were 7.82 among males and 11.76 among females. ORs increased sharply with every metric of smoking examined, more so for duration than for daily intensity. In models using continuous smoking variables, all metrics had strong effects on OR and mutual adjustment among smoking metrics did not noticeably attenuate the OR estimates, indicating that each metric carries some independent risk-related information. Among all the models tested, the one based on a smoking index that integrates several smoking dimensions, provided the best fitting model. Similar patterns were observed for the different histologic types of lung cancer. Conclusions This study provides many estimates of exposure-response relationships between smoking and lung cancer; these can be used in future meta-analyses. Irrespective of the histologic type of lung cancer and the smoking metric examined, high levels of smoking led to high levels of risk, for both men and women.

Objective: To evaluate the impact of the COVID-19 pandemic on preterm birth (PB) and low birth weight (LBW), comparing public and private healthcare systems of the National Integrated Health System in Uruguay, where the mitigation measures for the COVID-19 pandemic generated an immediate socioeconomic and psychological crisis, which caused a sharp widening of existing socioeconomic inequalities., Methods: A national observational study was conducted comparing perinatal outcomes in the first 6 months of 2020 (period of the pandemic without pregnancy infections), which was the beginning of the pandemic, with the same period of the previous year 2019 (pre-pandemic period with no mitigation measures) among pregnant women from the public and private health systems. Data were retrieved from the national database (Informatic Perinatal System) and analyzed by healthcare system category., Results: A total of 36 559 deliveries were assessed: 18 563 in the 2019 study period and 17 996 in the 2020 study period. In the public system, there was a significant increase in the risk of LBW (adjusted relative risk [aRR] 1.12, 95% confidence interval [CI] 1.05-1.36) and of the composite outcome (PB or LBW) (aRR 1.15, 95% CI 1.04-1.26). In the private system, by contrast, there was a non-statistically significant decrease of LBW and there were no changes in the incidence of PB and the composite outcome in 2020., Conclusion: The different evolution of birth outcomes in the public and private systems suggests an unequal impact of mitigation measures on populations of different socioeconomic levels. Given that no COVID-19 infections were identified in pregnant women during the study period, this research offers an opportunity to differentiate the biologic effects of the virus from the psychological and social impacts derived from containment measures., Gov Identifier: NCT05087160., (© 2023 International Federation of Gynecology and Obstetrics.)

Background: Few epidemiologic findings are as well established as the association between smoking and lung cancer. It is therefore somewhat surprising that there is not yet a clear consensus about the exposure-response relationships between various metrics of smoking and lung cancer risk. In part this is due to heterogeneity of how exposure-response results have been presented and the relative paucity of published results using any particular metric of exposure. The purposes of this study are: to provide new data on smoking-lung cancer associations and to explore the relative impact of different dimensions of smoking history on lung cancer risk., Methods: Based on a large lung cancer case-control study (1203 cases and 1513 controls) conducted in Montreal in 1996-2000, we estimated the lifetime prevalence of smoking and odds ratios in relation to several smoking metrics, both categorical and continuous based on multivariable unconditional logistic regression., Results: Odds ratios (ORs) for ever vs never smoking were 7.82 among males and 11.76 among females. ORs increased sharply with every metric of smoking examined, more so for duration than for daily intensity. In models using continuous smoking variables, all metrics had strong effects on OR and mutual adjustment among smoking metrics did not noticeably attenuate the OR estimates, indicating that each metric carries some independent risk-related information. Among all the models tested, the one based on a smoking index that integrates several smoking dimensions, provided the best fitting model. Similar patterns were observed for the different histologic types of lung cancer., Conclusions: This study provides many estimates of exposure-response relationships between smoking and lung cancer; these can be used in future meta-analyses. Irrespective of the histologic type of lung cancer and the smoking metric examined, high levels of smoking led to high levels of risk, for both men and women.

Objectives: We developed a job-exposure matrix called CANJEM using data generated in population-based case-control studies of cancer. This article describes some of the decisions in developing CANJEM, and some of its performance characteristics., Methods: CANJEM is built from exposure information from 31673 jobs held by study subjects included in our past case-control studies. For each job, experts had evaluated the intensity, frequency, and likelihood of exposure to a predefined list of agents based on jobs histories and descriptions of tasks and workplaces. The creation of CANJEM involved a host of decisions regarding the structure of CANJEM, and operational decisions regarding which parameters to present. The goal was to produce an instrument that would provide great flexibility to the user. In addition to describing these decisions, we conducted analyses to assess how well CANJEM covered the range of occupations found in Canada., Results: Even at quite a high level of resolution of the occupation classifications and time periods, over 90% of the recent Canadian working population would be covered by CANJEM. Prevalence of exposure of specific agents in specific occupations ranges from 0% to nearly 100%, thereby providing the user with basic information to discriminate exposed from unexposed workers. Furthermore, among exposed workers there is information that can be used to discriminate those with high exposure from those with low exposure., Conclusions: CANJEM provides good coverage of the Canadian working population and possibly that of several other countries. Available in several occupation classification systems and including 258 agents, CANJEM can be used to support exposure assessment efforts in epidemiology and prevention of occupational diseases.

Purpose: The purpose of this study was to describe time trends in response rates in case-control studies of cancer and identify study design factors that influence response rate., Methods: We reviewed 370 case-control studies of cancer published in 12 journals during indicator years in each of the last four decades. We estimated time trends of response rates and reasons for nonresponse in each of the following types of study subjects: cases, medical source controls, and population controls. We also estimated response rates according to characteristics of study context., Results: Median response rates among cases and population controls were between 75% and 80% in the 1970s. Between 1971 and 2010, study response rates declined by 0.31% per year for cases and 0.78% for population controls. Only a minority of studies reported reasons for nonparticipation; subject refusal was the most common reported reason. Studies conducted in North America had lower median response rates than studies conducted in Europe. In-person and telephone interviews elicited higher response rates than mail questionnaires., Conclusions: Response rates from case-control studies of cancer have declined, and this could threaten the validity of results derived from these studies., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objectives: Estimates of association between exposures and diseases are often distorted by error in exposure classification. When the validity of exposure assessment is known, this can be used to adjust these estimates. When exposure is assessed by experts, even if validity is not known, we sometimes have information about interrater reliability. We present a Bayesian method for translating the knowledge of interrater reliability, which is often available, into knowledge about validity, which is often needed but not directly available, and applying this to correct odds ratios (OR)., Methods: The method allows for inclusion of observed potential confounders in the analysis, as is common in regression-based control for confounding. Our method uses a novel type of prior on sensitivity and specificity. The approach is illustrated with data from a case-control study of lung cancer risk and occupational exposure to diesel engine emissions, in which exposure assessment was made by detailed job history interviews with study subjects followed by expert judgement., Results: Using interrater agreement measured by kappas (κ), we estimate sensitivity and specificity of exposure assessment and derive misclassification-corrected confounder-adjusted OR. Misclassification-corrected and confounder-adjusted OR obtained with the most defensible prior had a posterior distribution centre of 1.6 with 95% credible interval (Crl) 1.1 to 2.6. This was on average greater in magnitude than frequentist point estimate of 1.3 (95% Crl 1.0 to 1.7)., Conclusions: The method yields insights into the degree of exposure misclassification and appears to reduce attenuation bias due to misclassification of exposure while the estimated uncertainty increased., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Purpose: Although evidence has accumulated that recreational physical activities (PA) may reduce lung cancer risk, there is little evidence concerning the possible role of a potentially more important source of PA, namely occupational PA. We investigated both recreational and lifetime occupational PA in relation to lung cancer risk in a population-based case-control study in Montreal, Canada (N CASES  = 727; N CONTROLS  = 1,351)., Methods: Unconditional logistic regression was used to estimate odds ratios (OR), separately for men and women, adjusting for smoking, exposure to occupational carcinogens, and sociodemographic and lifestyle factors., Results: In both sexes, increasing recreational PA was associated with a lower lung cancer risk (OR MEN  = 0.66, 95% confidence interval (CI) 0.47-0.92; OR WOMEN  = 0.55, 95% CI 0.34-0.88, comparing the highest versus lowest tertiles). For occupational PA, no association was observed among women, while increasing occupational PA was associated with increased risk among men (OR MEN  = 1.96, 95% CI 1.27-3.01). ORs were not modified by occupational lung carcinogen exposure, body mass index, and smoking level; results were similar across lung cancer histological types., Conclusions: Our results support the previous findings for recreational PA and lung cancer risk. Unexpectedly, our findings suggest a positive association for occupational PA; this requires replication and more detailed investigation.

Background: Given the large number of workers in the construction industry, it is important to derive accurate and valid estimates of cancer risk, and in particular lung cancer risk. In most previous studies, risks among construction workers were compared with general populations including blue and white collar workers. The main objectives of this study were to assess whether construction workers experience excess lung cancer risk, and whether exposure to selected construction industry exposures carries excess risks. We wished to address these objectives within the sub-population of blue collar workers., Methods: Two case-control studies were conducted in Montreal. Combined, they included 1593 lung cancer cases and 1427 controls, of whom 1304 cases and 1081 controls had been blue collar workers. Detailed lifetime job histories were obtained and translated by experts into histories of exposure to chemical agents. The two key analyses were to estimate odds ratio (OR) estimates of lung cancer risk: a) for all blue-collar construction workers compared with other blue-collar workers, and b) for construction workers exposed to each of 20 exposure agents found in the construction industry compared with construction workers unexposed to those agents. All analyses were conducted using unconditional logistic regression adjusted for socio-demographic factors and smoking history., Results: The OR for all construction workers combined was 1.11 (95 % CI: 0.90-1.38), based on 381 blue collar construction workers. Analyses of specific exposures were hampered by small numbers and imprecise estimates. While none of 20 occupational agents examined was significantly associated with lung cancer, the following agents manifested non-significantly elevated ORs: asbestos, silica, Portland cement, soil dust, calcium oxide and calcium sulfate., Conclusions: Compared with other blue collar workers, there was only a slight increased risk of lung cancer for subjects who ever held an occupation in the construction industry. The analyses of agents within the construction industry produced imprecise estimates of risk, but nevertheless pointed to some plausible associations. Excess risks for asbestos and silica were in line with previous knowledge. The possible excess risks with the other inorganic dusts require further corroboration.

Objectives: To investigate the risk of lung cancer among cooks, while controlling for smoking habits., Methods: We used data from the SYNERGY project including pooled information on lifetime work histories and smoking habits from 16 case-control studies conducted in Europe, Canada, New Zealand, and China., Results: Before adjustment for smoking, we observed an increased risk of lung cancer in male cooks, but not in female cooks. After adjusting, there was no increased risk and no significant exposure-response relationship. Nevertheless, subgroup analyses highlighted some possible excess risks of squamous cell carcinoma and small cell carcinoma in female cooks., Conclusions: There is evidence that lung cancer risks among cooks may be confounded by smoking. After adjustment, cooks did not experience an increased risk of lung cancer overall. The subgroup analyses showing some excess risks among female cooks require cautious interpretation.

Background: Wood dust is one of the oldest and one of the most common occupational exposures in the world. The present analyses examine the effect of lifetime exposure to wood dust in diverse occupational settings on lung cancer risk., Methods: We conducted two population-based case-control studies in Montreal: Study I (1979-1986) included 857 cases and two sets of controls (533 population and 1349 cancer controls), and Study II (1996-2001) comprised 736 cases and 894 population controls. Detailed job histories were obtained by interview and each job was evaluated by expert chemist-hygienists to estimate the likelihood and level of exposure to many substances, one of which was wood dust. Odds ratios (ORs) were computed in relation to different indices of exposure to wood dust, adjusting for several covariates including smoking. Three datasets were analysed: Study I with population controls, Study I with cancer controls, and Study II., Results: The most frequently exposed occupations in our study population were in construction, timber and furniture making industries. We found increased risks of lung cancer for substantial cumulative exposure to wood dust in Study I with cancer controls, (OR = 1.4: 95% confidence interval 1.0;-2.0) and in Study II (OR = 1.7: 95% confidence interval 1.1-2.7). There were no excess risks of lung cancer in any of the three datasets among workers whose cumulative exposure was not substantial. These tendencies held equally within strata of low smokers and heavy smokers., Conclusion: There was evidence of increased risk of lung cancer among workers with substantial cumulative exposure to wood dust.

Objectives: The plaintiffs' lawyers for a class action suit, which was launched in Quebec on behalf of all patients with lung cancer whose disease was caused by cigarette smoking, asked us to estimate what proportion of lung cancer cases in Quebec, if they hypothetically could be individually evaluated, would satisfy the criterion that it is "more likely than not" that smoking caused the disease., Methods: The novel methodology we developed is based on the dose-response relationship between smoking and lung cancer, for which we use the pack-years as a measure of smoking, and the distribution of pack-years of smoking among cases., Results: We estimated that the amount of smoking required to satisfy the "more likely than not" criterion is between 3 and 11 pack-years. More than 90% of the Quebec cases satisfied even the most conservative of these thresholds., Conclusions: More than 90% of cases of lung cancer in Quebec are legally attributable to smoking. The methodology enhances the ability to conduct class action suits against the tobacco industry.

Background: The objective of the present study was to examine the association between environmental tobacco smoke (ETS) and risk of lung cancer among never smokers, defined as subjects who smoked less than 100 cigarettes in their lifetime., Methods: We conducted a population-based case-control study on lung cancer in Montreal, Canada (1996-2000) including 1,203 cases and 1513 controls. The present analysis is restricted to the 44 cases and 436 population controls who reported never smoking and completed the questionnaire on lifetime ETS exposure. Collected information included duration and intensity of exposure from multiple sources: inside home (parents, spouses, roommates and any other co-resident) and outside homes (in vehicles, social settings, and workplace). Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated between ETS and lung cancer, adjusting for age, sex, socioeconomic status (SES), and proxy respondent., Results: Overall there was no association between ETS cumulative exposure from all sources (measured in pack-years) and lung cancer: OR = 0.98 (95%CI: 0.40-2.38), comparing upper with lower tertiles of exposure. While there were no elevated ORs associated with ever having lived with parents who smoked (OR = 0.62; 95%CI: 0.32-1.21) or with spouses who smoked (OR = 0.39; 95%CI: 0.18-0.85), ETS exposure from sources outside homes was associated with a slight, although non-significant increased risk: OR = 2.30 (95%CI: 0.85-6.19) for the upper 50% exposed. There were no clear differences in ORs by age at exposure to ETS or by histologic type of tumour, though numbers of subjects in subgroup analyses were too small to provide reliable estimates., Conclusion: No clear association between lifetime ETS exposure from all sources and increased risk of lung cancer was found in the current study.

Background: The aim was to investigate possible associations between glioma (an aggressive type of brain cancer) and occupational exposure to selected agents: combustion products (diesel and gasoline exhaust emissions, benzo(a)pyrene), dusts (animal dust, asbestos, crystalline silica, wood dust) and some other chemical agents (formaldehyde, oil mist, sulphur dioxide)., Methods: The INTEROCC study included cases diagnosed with glioma during 2000-2004 in sub-regions of seven countries. Population controls, selected from various sampling frames in different centers, were frequency or individually matched to cases by sex, age and center. Face-to-face interviews with the subject or a proxy respondent were conducted by trained interviewers. Detailed information was collected on socio-economic and lifestyle characteristics, medical history and work history. Occupational exposure to the 10 selected agents was assessed by a job exposure matrix (JEM) which provides estimates of the probability and level of exposure for different occupations. Using a 25% probability of exposure in a given occupation in the JEM as the threshold for considering a worker exposed, the lifetime prevalence of exposure varied from about 1% to about 15% for the different agents. Associations between glioma and each of the 10 agents were estimated by conditional logistic regression, and using three separate exposure indices: i) ever vs. never; ii) lifetime cumulative exposure; iii) total duration of exposure., Results: The study sample consisted of 1,800 glioma cases and 5,160 controls. Most odds ratio estimates were close to the null value. None of the ten agents displayed a significantly increased odds ratio nor any indication of dose-response relationships with cumulative exposure or with duration of exposure., Conclusion: Thus, there was no evidence that these exposures influence risk of glioma.

Night work might influence cancer risk, possibly via suppression of melatonin release. In a population-based case-control study conducted in Montreal, Quebec, Canada, between 1979 and 1985, job histories, including work hours, were elicited from 3,137 males with incident cancer at one of 11 anatomic sites and from 512 controls. Compared with men who never worked at night, the adjusted odds ratios among men who ever worked at night were 1.76 (95% confidence interval (CI): 1.25, 2.47) for lung cancer, 2.03 (95% CI: 1.43, 2.89) for colon cancer, 1.74 (95% CI: 1.22, 2.49) for bladder cancer, 2.77 (95% CI: 1.96, 3.92) for prostate cancer, 2.09 (95% CI: 1.40, 3.14) for rectal cancer, 2.27 (95% CI: 1.24, 4.15) for pancreatic cancer, and 2.31 (95% CI: 1.48, 3.61) for non-Hodgkin's lymphoma. Equivocal evidence or no evidence was observed for cancers of the stomach (odds ratio (OR) = 1.34, 95% CI: 0.85, 2.10), kidney (OR = 1.42, 95% CI: 0.86, 2.35), and esophagus (OR = 1.51, 95% CI: 0.80, 2.84) and for melanoma (OR = 1.04, 95% CI: 0.49, 2.22). There was no evidence of increasing risk with increasing duration of night work, with risks generally being increased across all duration categories. Results suggest that night work may increase cancer risk at several sites among men.

Objective: To examine the risk of lung cancer among men associated with exposure to diesel engine emissions incurred in a wide range of occupations and industries., Methodology: 2 population-based lung cancer case-control studies were conducted in Montreal. Study I (1979-1986) comprised 857 cases and 533 population controls; study II (1996-2001) comprised 736 cases and 894 population controls. A detailed job history was obtained, from which we inferred lifetime occupational exposure to 294 agents, including diesel engine emissions. ORs were estimated for each study and in the pooled data set, adjusting for socio-demographic factors, smoking history and selected occupational carcinogens. While it proved impossible to retrospectively estimate absolute exposure concentrations, there were estimates and analyses by relative measures of cumulative exposure., Results: Increased risks of lung cancer were found in both studies. The pooled analysis showed an OR of lung cancer associated with substantial exposure to diesel exhaust of 1.80 (95% CI 1.3 to 2.6). The risk associated with substantial exposure was higher for squamous cell carcinomas (OR 2.09; 95% CI 1.3 to 3.2) than other histological types. Joint effects between diesel exhaust exposure and tobacco smoking are compatible with a multiplicative synergistic effect., Discussion: Our findings provide further evidence supporting a causal link between diesel engine emissions and risk of lung cancer. The risk is stronger for the development of squamous cell carcinomas than for small cell tumours or adenocarcinomas.

We investigated relationships between occupational exposure to gas and arc welding fumes and the risk of lung cancer among workers exposed to these agents throughout the spectrum of industries. Two population-based case-control studies were conducted in Montreal. Study I (1979-1986) included 857 cases and 1066 controls, and Study II (1996-2001) comprised 736 cases and 894 controls. Detailed job histories were obtained by interview and evaluated by an expert team of chemist-hygienists to estimate degree of exposure to approximately 300 substances for each job. Gas and arc welding fumes were among the agents evaluated. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) of lung cancer using logistic regression, adjusting for smoking history and other covariates. The two studies provided similar results, so a pooled analysis was conducted. Among all subjects, no significant association was found between lung cancer and gas welding fumes (OR = 1.1; 95% CI = 0.9-1.4) or arc welding fumes (OR = 1.0; 95% CI = 0.8-1.2). However, when restricting attention to light smokers, there was an increased risk of lung cancer in relation to gas welding fumes (OR = 2.9; 95% CI = 1.7-4.8) and arc welding fumes (OR = 2.3; 95% CI = 1.3-3.8), with even higher OR estimates among workers with the highest cumulative exposures. In conclusion, there was no detectable excess risk of lung cancer due to welding fumes among moderate to heavy smokers; but among light smokers we found an excess risk related to both types of welding fumes.

Context: Retrospective exposure assessment in population-based case-control studies poses a major challenge due to the wide range of occupations and industries involved. The FINJEM is a generic job-exposure matrix (JEM) developed in Finland, which represents a potentially cost-effective exposure assessment tool. While FINJEM has been used in several studies outside Finland, little is known of its applicability in other countries., Methods: We compared prevalence and intensity of exposure in FINJEM with a JEM developed from expert assessments of occupational histories obtained in a population-based case-control study in Montreal. Agreement for prevalence of exposure was measured by weighted κ coefficients between prevalence categories. Agreement for exposure intensity was measured by Spearman correlation coefficients between cells with non-null exposure., Results: The comparison involved 27 chemicals, the time period 1945-1995 and included 4743 jobs initially assessed by the Montreal experts. 4293 combinations of agent, occupational title and period were available for comparison of prevalence. Agent-specific prevalence was consistently higher in the Montreal JEM (median difference 1.7%). Agent-specific κ values between prevalence categories varied from 0.89 (welding fumes) to 0.07 (flour dust). The comparison of exposure levels involved 14 agents and 198 cells with non-null exposure in both sources. Agent-specific Spearman correlation varied from 0.89 (flour dust) to -0.35 (benzo(a)pyrene)., Conclusion: Our observations suggest that information concerning several agents (eg, metals, welding fumes) can be successfully transported from Finland to Canada and probably other countries. However, for other agents, there was considerable disagreement, and hence, transportability of FINJEM cannot be assumed by default.

It has been hypothesized that flavonoids in foods and beverages may reduce cancer risk through antioxidation, inhibition of inflammation, and other antimutagenic and antiproliferative properties. We examined associations between intake of 5 flavonoid subclasses (anthocyanidins, flavan-3-ols, flavones, flavonols, and flavanones) and lung cancer risk in a population-based case-control study in Montreal, Canada (1061 cases and 1425 controls). Flavonoid intake was estimated from a food frequency questionnaire that assessed diet 2 yr prior to diagnosis (cases) or interview (controls). Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression. Overall, total flavonoid intake was not associated with lung cancer risk, the effect being similar regardless of sex and smoking level. However, low flavonoid intake from food, but not from beverages, was associated with an increased risk. The adjusted ORs (95% CIs) comparing the highest vs. the lowest quartiles of intake were 0.63 (0.47-0.85) for total flavonoids, 0.82 (0.61-1.11) for anthocyanidins, 0.67 (0.50-0.90) for flavan-3-ols, 0.68 (0.50-0.93) for flavones, 0.62 (0.45-0.84) for flavonols, and 0.70 (0.53-0.94) for flavanones. An inverse association with total flavone and flavanone intake was observed for squamous cell carcinoma but not adenocarcinoma. In conclusion, low flavonoid intake from food may increase lung cancer risk.

Background: Since individual-level income is difficult to collect, investigators often rely on group-based measures derived from census data. No study has assessed the use of residential property values as an indicator of individual material circumstances. We aimed to compare two proxy indicators of material circumstances, one based on residential value and the other on median census tract income, to self-reported household income., Methods: We used data from a case-control study (1996-2002), restricting analyses to 676 residents of the Island of Montreal for whom the three indicators were available. The degree of discrepancy between the residential value index, census income, and self-reported household income--each in 5 categories--was estimated, along with overall and weighted Kappas., Results: When comparing residential value index and census income to self-reported household income, perfect concordance was observed for 38% and 30% of subjects, respectively; very good concordance, defined as ≤1 category difference, was observed for 76% and 69% of subjects, respectively. When compared to self-reported household income, overall and weighted Kappas showed stronger agreement with residential value index (weighted Kappa=0.37, 95% CI: 0.32, 0.42) than with census income (weighted Kappa=0.25, 95% CI: 0.20, 0.30)., Conclusions: A residential value index may provide a measure of material circumstances that is closer to self-reported household income than the commonly used census income. Each indicator presents advantages and disadvantages, and their choice may depend on study objectives and feasibility.

Rationale: Diesel motor exhaust is classified by the International Agency for Research on Cancer as probably carcinogenic to humans. The epidemiologic evidence is evaluated as limited because most studies lack adequate control for potential confounders and only a few studies have reported on exposure-response relationships., Objectives: Investigate lung cancer risk associated with occupational exposure to diesel motor exhaust, while controlling for potential confounders., Methods: The SYNERGY project pooled information on lifetime work histories and tobacco smoking from 13,304 cases and 16,282 controls from 11 case-control studies conducted in Europe and Canada. A general population job exposure matrix based on ISCO-68 occupational codes, assigning no, low, or high exposure to diesel motor exhaust, was applied to determine level of exposure., Measurements and Main Results: Odds ratios of lung cancer and 95% confidence intervals were estimated by unconditional logistic regression, adjusted for age, sex, study, ever-employment in an occupation with established lung cancer risk, cigarette pack-years, and time-since-quitting smoking. Cumulative diesel exposure was associated with an increased lung cancer risk highest quartile versus unexposed (odds ratio 1.31; 95% confidence interval, 1.19-1.43), and a significant exposure-response relationship (P value < 0.01). Corresponding effect estimates were similar in workers never employed in occupations with established lung cancer risk, and in women and never-smokers, although not statistically significant., Conclusions: Our results show a consistent association between occupational exposure to diesel motor exhaust and increased risk of lung cancer. This association is unlikely explained by bias or confounding, which we addressed by adjusted models and subgroup analyses.

Background: Respirable crystalline silica is a highly prevalent occupational exposure and a recognized lung carcinogen. Most previous studies have focused on selected high-exposure occupational groups. This study examines the relationship between occupational exposure to silica and lung cancer in an occupationally diverse male population., Methods: Two large population-based case-control studies of lung cancer were conducted in Montreal, one in 1979-1986 (857 cases, 533 population controls, 1,349 cancer controls) and the second in 1996-2001 (738 cases and 899 controls). Interviews provided descriptive lifetime job histories, smoking histories, and other information. Industrial hygienists translated job histories into histories of exposure to a host of occupational substances, including silica. Relative risk was estimated, adjusting for several potential confounders, including smoking., Results: The odds ratio for substantial exposure to silica was 1.67 (95% confidence interval, 1.21-2.31) and for any exposure was 1.31 (95% confidence interval, 1.08-1.59). Joint effects between silica and smoking were between additive and multiplicative, perhaps closer to the latter. In this population, it is estimated that approximately 3% of lung cancers were attributable to substantial silica exposure., Conclusions: The carcinogenicity of inhaled crystalline silica was observed in a population with a wide variety of exposure circumstances., Impact: The finding of carcinogenicity across a wide range of occupations complements prior studies of specific high-exposure occupations. This suggests that the burden of cancer induced by silica may be much greater than previously thought., (Copyright 2010 AACR.)

Background: Nickel, chromium VI, and cadmium have been identified as lung carcinogens in highly exposed cohorts. The purpose of this study was to examine the etiological link between lung cancer and these metals in occupations, that usually entail lower levels of exposure than those seen in historical cohorts., Methods: Two population-based case-control studies were conducted in Montreal, from 1979 to 1986 and from 1996 to 2001, comprising 1,598 cases and 1,965 controls. A detailed job history was obtained to evaluate lifetime occupational exposure to many agents, including nickel, chromium VI, and cadmium compounds., Results: Lung cancer odds ratios were increased only among former or non-smokers: 2.5 (95% CI: 1.3-4.7) for nickel exposure, 2.4 (95% CI: 1.2-4.8) for chromium VI, and 4.7 (95% CI: 1.5-14.3) for cadmium. The metals did not increase risk among smokers., Conclusions: While excess risks due to these metal compounds were barely discernable among smokers, carcinogenic effects were seen among non-smokers., (2010 Wiley-Liss, Inc.)

Objective: To examine the effects of exposure to occupational asbestos and man-made vitreous fibers (MMVF) across a wide range of occupations on risk of mesothelioma., Methodology: Two population-based case-control studies (1979-1986 and 1996-2001) provided 35 histologically confirmed mesothelioma cases and 1965 controls. A detailed job history was obtained to evaluate occupational exposure to many agents, including asbestos and MMVF., Results: The mesothelioma odds ratio for exposure to any asbestos type was 3.7 (95% confidence interval = 1.7 to 7.8). The subset exposed to amphibole fibers experienced an odds ratio = 7.0 (95% confidence interval = 2.7 to 18.5). Effects of MMVF could not be disentangled from those of asbestos., Discussion: In workers with exposure levels lower than in most historical cohort studies and across a wide range of industries, a strong association was found between asbestos, especially when it was amphibole, and mesothelioma.

Objective: To examine the effects of occupational asbestos and man-made vitreous fibers (MMVF) on the risk of lung cancer in two population-based case-control studies entailing exposure at lower levels than in historic cohort studies., Methodology: Study I (1979 to 1986) comprised 857 cases and 1066 population and cancer controls. Study II (1996 to 2001) comprised 858 cases and 1295 population controls. A detailed job history was obtained to evaluate lifetime occupational exposure to 294 agents, including asbestos and MMVF., Results: We found increased risks for substantial exposure to asbestos (odds ratio = 1.78; 95% confidence interval: 0.94 to 3.36). The corresponding odds ratio for substantial exposure to MMVF was 1.10 (95% confidence interval: 0.37 to 3.22)., Discussion: Low and moderate levels of exposure to asbestos, as encountered in this population, were associated with some excess risk of lung cancer. Results for MMVF were inconclusive.

The objective of the present study was to examine the association between human papillomavirus (HPV) infection and risk of developing oral cancer. The investigation followed a hospital-based case-control design. Cases consisted of newly diagnosed patients with squamous cell carcinoma of the oral cavity and oropharynx. Controls were frequency matched to cases on gender, age, and hospital. Subjects were interviewed to elicit information on putative risk factors. Oral exfoliated cells were tested for detection of HPV DNA by the PGMY09/11 polymerase chain reaction protocol. Serum antibodies against HPV 16, 18, and 31 viral capsids were detected using an immunoassay technique. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) of oral cancer according to HPV exposure variables. HPV DNA was detected in 19% of cases (14 out of 72), and 5% of controls (six out of 129). Among tonsil-related cancers (palatine tonsil and base of tongue) viral DNA was detected in 43% of cases (nine out of 21). The OR for tonsil-related cancers for high-risk HPV types was 19.32 (95%CI: 2.3-159.5), after adjustment for socio-demographic characteristics, tobacco, and alcohol consumption. The equivalent OR for HPV 16 seropositivity was 31.51 (95%CI: 4.5-219.7). The ORs of non-tonsillar oral cancers for high risk HPV DNA in oral cells and for seropositivity were 2.14 (95%CI: 0.4-13.0) and 3.16 (95%CI: 0.8-13.0), respectively. These results provide evidence supporting a strong causal association between HPV infection and tonsil-related cancers. The evidence for an etiologic link is less clear for non-tonsillar oral cancers.

To assess the performance of human papillomavirus (HPV) testing and colposcopy in detection of cervical pathology. A series of 389 women referred for colposcopy due to an abnormal Pap smear had cervical swabs analyzed for oncogenic (high-risk [HR]) HPV types using Hybrid Capture II (HC2) assay. Loop electrical excision procedure cone biopsy (88%) or colposcopic biopsy (11%) was used as the gold standard. Of the atypical squamous cells of undetermined significance (ASCUS) smears, 48% were positive for HR HPV, as compared to 76.3% of low-grade squamous intraepithelial lesions (LSIL) smears. HR HPV was detected in 66.7% and 90% of patients with cervical intraepithelial neoplasia (CIN) 1 and CIN2 (or higher), respectively. The sensitivity of the Pap smear using an ASCUS threshold in detecting high-grade CIN was 94.5% (95% confidence intervals (CI): 91-97%) and that of colposcopy 98.5% (95% CI: 95-99%). The respective specificities were 30% (95% CI: 17-28%) and 35.6% (CI: 29-42%). HC2 test had comparable sensitivity, 90% (95% CI: 85-93%), but higher specificity, 54.3% (95% CI: 47-61%). Combining HC2 test with Pap increased specificity, 66.7% and 41.3% for ASCUS and LSIL cutoff, respectively. The minor-abnormality threshold together with HC2 increased specificity of colposcopy with no changes in sensitivity. High viral load (>100 relative light unit/positive control) was associated with significant disease. HPV DNA testing improves the accuracy of colposcopy in the detection of high-grade CIN in women with ASCUS or LSIL smears.

Background: High risk patients with metastatic non small cell lung cancer (NSCLC) including patients with performance status (PS) 2 or elderly with comorbidities do poorly on combination chemotherapy regimens. We evaluated a sequential treatment with Vinorelbine followed by Gemcitabine to determine its effect on survival and the toxicity in this patient population., Methods: Forty-two evaluable patients, median age 75, 21 patients with PS 2 and 21 patients with PS 0 or 1, 37 patients with stage IV and five patients with stage III B NSCLC entered the trial. They received Vinorelbine 30 mg/m2, i.v., on days 1+8 every 3 weeks followed by Gemcitabine 1000 mg/m2, i.v., on days 1+8 every 3 weeks, each for two cycles for stable disease or one cycle after best response. Then stable patients continued until progressive disease on Vinorelbine or Gemcitabine according to the patient's preference., Results: A total of 126 cycles of Vinorelbine were administered to 42 patients, median of three cycles per patient and 74 cycles of Gemcitabine, median of 1.0 cycle per patient. Sixteen patients (38%) achieved PR, 11 patients on Vinorelbine, 5 patients on Gemcitabine; 12 patients (26%) had stable disease, 7 patients on Vinorelbine, 5 patients on Gemcitabine. Of 24 patients with progressive disease on Vinorelbine, 3 patients (12.5%) responded to Gemcitabine. Median time-to-first progression was 3.5 months, median survival was 8 months, 1-year survival was 12 patients (28.5%). No grade 3 or 4 toxicities were reported., Conclusion: This sequential treatment offers excellent palliative treatment with minimal toxicity for high-risk patients with metastatic NSCLC.

The Saguenay-Lac St-Jean population of Quebec is relatively isolated and has genealogical records dating to the 17th-century French founders. In 120 extended families with at least one sib pair affected with early-onset hypertension and/or dyslipidemia, we analyzed the genetic determinants of hypertension and related cardiovascular and metabolic conditions. Variance-components linkage analysis revealed 46 loci after 100,000 permutations. The most prominent clusters of overlapping quantitative-trait loci were on chromosomes 1 and 3, a finding supported by principal-components and bivariate analyses. These genetic determinants were further tested by classifying families by use of LOD score density analysis for each measured phenotype at every 5 cM. Our study showed the founder effect over several generations and classes of living individuals. This quantitative genealogical approach supports the notion of the ancestral causality of traits uniquely present and inherited in distinct family classes. With the founder effect, traits determined within population subsets are measurably and quantitatively transmitted through generational lineage, with a precise component contributing to phenotypic variance. These methods should accelerate the uncovering of causal haplotypes in complex diseases such as hypertension and metabolic syndrome.