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In this issue of the Journal, Savitz and Wellenius (Am J Epidemiol. 2023;192(4):514–516) discuss the contribution of cross-sectional studies to causal inference when the data are used to address etiological research questions. We elaborate on their thoughts with a discussion of the conditions needed for addressing etiology with the cross-sectional design, using a modern causal inference lens.

Introduction High-quality epidemiological evidence on the relationship between the occupational environment and ovarian cancer risk is limited. Most studies had very few cases, did not adjust for important confounders, and lacked information on specific workplace exposures. Objectives To investigate the relationship between occupation, specific workplace exposures, and ovarian cancer risk. Methods In a population-based case-control study conducted in Montreal, Canada (2011–2016), lifetime occupational histories were collected for 492 cases and 897 controls. For each job held by a participant, occupational and industrial classification codes were coded by an industrial hygienist. To identify specific workplace exposures, job codes were linked to the Canadian job-exposure matrix. Twenty-three agents with relatively high prevalence were selected. Occupations were examined by comparing participants ever employed in a given occupation for at least ten years vs. never employed in that occupation. For specific exposures, ever exposure, exposure duration, and cumulative exposure to selected agents were analyzed. Odds ratios (OR) and 95% confidence intervals (CI) for associations with ovarian cancer risk were estimated using logistic regression. Results Elevated ORs were observed for accountants (OR=2.03, 95% CI: 1.09–3.76); hairdressers, barbers, and beauticians (OR=3.22, 95% CI: 1.25–8.28); sewers and embroiderers (OR=1.89, 95% CI: 0.78–4.59); saleswomen, shop assistants, and demonstrators (OR=1.42, 95% CI: 0.70–2.89); and occupations in retail trade (OR=1.59, 95% CI: 1.05–2.39). For specific exposures, increased risks were suggested for cosmetic talc, ammonia, hydrogen peroxide, hair dust, propellant gases, fluorocarbons, ethanol, cellulose, and polyester fibres. Hairdressers, barbers, and beauticians were the most frequent occupation exposed to six out of nine specific workplace exposures among participants. Conclusion Study results suggest that certain occupations may be associated with increased ovarian cancer risks, but it is difficult to determine specific exposures that may contribute to the increased risks. Future larger studies with expert assessments of specific occupational exposures may better characterize co-exposures.

Objective We assessed whether human papillomavirus (HPV) viral load is an independent predictor of underlying cervical disease and its diagnostic accuracy by age. Methods The Biomarkers of Cervical Cancer Risk study was a case-control study from 2001 to 2010 in Montreal, Canada. Cases were histologically-confirmed cervical intraepithelial neoplasia (CIN), adenocarcinoma in situ (AIS), or cervical cancer cases. Controls were women presenting for routine screening with normal cytology results. We quantified HPV16/18/31/33/45 viral load from exfoliated cervical cells using a real-time PCR assay. Diagnostic accuracy of viral load was assessed using the area under the receiver operating characteristic curve (AUC). We restricted the analysis to the 632 cases and controls who were HPV16/18/31/33/45 positive. Results Geometric mean HPV16/18/31/33/45 viral load increased with severity of lesion grade, ranging from 0.7, 3.1, 4.8, 7.2, and 12.4 copies/cell in normal, CIN1, CIN2, CIN3&AIS, and cervical cancer respectively. The adjusted odds ratio of CIN1+ and CIN2+ increased respectively by 1.3 (95%CI 1.1–1.4) and 1.2 (95%CI 1.1–1.3) per log-transformed viral copy/cell increase of HPV16/18/31/33/45. This association was mainly driven by HPV16, 18, and 31 viral loads. The AUC of HPV16/18/31/33/45 viral load for discriminating between normal and CIN1+ women was 0.70 (95%CI 0.64–0.76) in HPV-positive women, and was 0.76 (95%CI 0.66–0.86) for women ≥30 years and 0.66 (95%CI 0.58–0.74) for women under 30 years. Conclusions HPV viral load has lower diagnostic accuracy than has been reported for other HPV screening triage tests. However, it may be useful for triaging HPV tests in settings without cytology results such as HPV self-sampling.

Results of epidemiologic studies of physical activity and ovarian cancer risk are inconsistent. Few have attempted to measure physical activity over the lifetime or in specific age windows, which may better capture etiologically relevant exposures. We examined participation in moderate-to-vigorous recreational physical activity (MVPA) in relation to ovarian cancer risk. In a population-based case-control study conducted in Montreal, Canada from 2011 to 2016 (485 cases and 887 controls), information was collected on lifetime participation in various recreational physical activities, which was used to estimate MVPA for each participant. MVPA was represented as average energy expenditure over the lifetime and in specific age-periods in units of metabolic equivalents (METs)-hours per week. Odds ratios (OR) and 95% confidence intervals (CI) for the relation between average MVPA and ovarian cancer risk were estimated using multivariable logistic regression models. Confounding was assessed using directed acyclic graphs combined with a change-in-estimate approach. The adjusted OR (95% CI) for each 28.5 MET-hr/week increment of lifetime recreational MVPA was 1.11 (0.99-1.24) for ovarian cancer overall. ORs for individual age-periods were weaker. When examined by menopausal status, the OR (95% CI) for lifetime MVPA was 1.21 (1.00-1.45) for those diagnosed before menopause and 1.04 (0.89-1.21) for those diagnosed postmenopausally. The suggestive positive associations were stronger for invasive ovarian cancers and more specifically for high-grade serous carcinomas. These results do not support a reduced ovarian cancer risk associated with MVPA.

Background: Shift work causing circadian disruption is classified as a “probable carcinogen” and may contribute to the pathogenesis of hormone-sensitive cancers. This study investigated shift work exposure in relation to epithelial ovarian cancer (EOC) risk. Methods: In a population-based case–control study with 496 EOC cases and 906 controls, lifetime occupational histories were collected and used to calculate cumulative years of shift work exposure, average number of night shifts per month, and average number of consecutive night shifts per month. ORs and 95% confidence intervals (CI) for associations with EOC risk were estimated using logistic regression. Associations were also examined according to chronotype and menopausal status. Results: More than half of the cases (53.4%) and controls (51.7%) worked evening and/or night shifts. There was no clear pattern of increasing EOC risk with increasing years of shift work; the adjusted OR of EOC comparing the highest shift work category versus never working shift work was 1.20 (95% CI, 0.89–1.63). This association was more pronounced among those self-identified as having a “morning” chronotype (OR, 1.64; 95% CI, 1.01–2.65). Associations did not greatly differ by menopausal status. Conclusions: These results do not strongly demonstrate a relationship between shift work and EOC risk. Impact: This study collected detailed shift work information and examined shift work patterns according to shift times and schedules. The findings highlight that chronotype should be considered in studies of shift work as an exposure.

DNA methylation is instrumental for gene regulation. Global changes in the epigenetic landscape have been recognized as a hallmark of cancer. However, the role of DNA methylation in epithelial ovarian cancer (EOC) remains unclear. In this study, high-density genetic and DNA methylation data in white blood cells from the Framingham Heart Study (N = 1,595) were used to build genetic models to predict DNA methylation levels. These prediction models were then applied to the summary statistics of a genome-wide association study (GWAS) of ovarian cancer including 22,406 EOC cases and 40,941 controls to investigate genetically predicted DNA methylation levels in association with EOC risk. Among 62,938 CpG sites investigated, genetically predicted methylation levels at 89 CpG were significantly associated with EOC risk at a Bonferroni-corrected threshold of P < 7.94 × 10−7. Of them, 87 were located at GWAS-identified EOC susceptibility regions and two resided in a genomic region not previously reported to be associated with EOC risk. Integrative analyses of genetic, methylation, and gene expression data identified consistent directions of associations across 12 CpG, five genes, and EOC risk, suggesting that methylation at these 12 CpG may influence EOC risk by regulating expression of these five genes, namely MAPT, HOXB3, ABHD8, ARHGAP27, and SKAP1. We identified novel DNA methylation markers associated with EOC risk and propose that methylation at multiple CpG may affect EOC risk via regulation of gene expression. Significance: Identification of novel DNA methylation markers associated with EOC risk suggests that methylation at multiple CpG may affect EOC risk through regulation of gene expression.

Owing to the rapidly evolving coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, quick public health investigations of the relationships between behaviors and infection risk are essential. Recently the test-negative design (TND) was proposed to recruit and survey participants who are symptomatic and being tested for SARS-CoV-2 infection with the goal of evaluating associations between the survey responses (including behaviors and environment) and testing positive on the test. It was also proposed to recruit additional controls who are part of the general population as a baseline comparison group to evaluate risk factors specific to SARS-CoV-2 infection. In this study, we consider an alternative design where we recruit among all individuals, symptomatic and asymptomatic, being tested for the virus in addition to population controls. We define a regression parameter related to a prospective risk factor analysis and investigate its identifiability under the two study designs. We review the difference between the prospective risk factor parameter and the parameter targeted in the typical TND where only symptomatic and tested people are recruited. Using missing data directed acyclic graphs, we provide conditions and required data collection under which identifiability of the prospective risk factor parameter is possible and compare the benefits and limitations of the alternative study designs and target parameters. We propose a novel inverse probability weighting estimator and demonstrate the performance of this estimator through simulation study.

Background Caffeine intake has been inconsistently associated with the risk of ovarian cancer in previous studies. The measure of caffeine in these studies has not always distinguished between caffeinated and decaffeinated sources, and the time for which intake was assessed was often for late adulthood and thus may have excluded the etiologic window. We investigated lifetime caffeine intake from caffeinated coffee, black tea, green tea and cola sodas in relation to ovarian cancer risk. Methods Among 497 cases and 904 controls in a population-based case-control study in Montreal, Canada, lifetime intake of caffeinated coffee, black tea, green tea and cola sodas was assessed and used to calculate lifetime total intake of caffeine. Unconditional multivariable logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for the association between caffeine intake and ovarian cancer risk overall, as well as by menopausal status. Multivariable polytomous logistic regression was used to estimate the associations for invasive and borderline ovarian cancers separately. Results Almost all participants (98.4% of cases and 97.5% of controls) had consumed caffeine in their lifetime. The mean (standard deviation) daily consumption of caffeine over the lifetime was of 117 (89) mg/day among cases and 120 (118) mg/day among controls. The OR (95% CI) of ovarian cancer for the highest versus lowest quartile of lifetime caffeine intake was 1.17 (0.83–1.64). According to menopausal status, the OR (95% CI) was 1.56 (0.85–2.86) for premenopausal women and 0.94 (0.66–1.34) for postmenopausal women, comparing the highest to lowest tertiles of intake. Associations for invasive and borderline ovarian cancers separately were similar to that observed for ovarian cancer overall. Conclusion Lifetime caffeine intake was not strongly associated with ovarian cancer risk. A difference in relationship by menopausal status is possible.

Given the poor prognosis of ovarian cancer and limited population-level strategies for early detection and long-term treatment success, knowledge of modifiable risk factors for prevention and improved prognosis is important. Vitamin D has received wide scientific interest in cancer research as having the potential to be one such factor. We carried out a systematic narrative review of the literature on vitamin D and ovarian cancer risk and survival. We included 17 case-control and cohort studies on ovarian cancer incidence. Five analyses were of sun exposure, among which three reported an inverse association. Of 11 analyses of dietary vitamin D, two reported an inverse association. Among five studies of 25(OH)D levels, an inverse association was reported in two. Across all studies the findings were inconsistent, but some recent studies have suggested that vitamin D exposure at earlier ages may be important. Only three studies examining vitamin D exposure in relation to survival among ovarian cancer survivors were identified and the findings were inconsistent. The evidence to date supports a null influence of vitamin D on both ovarian cancer risk and survival. Future research should ensure that exposure assessment captures vitamin D exposure from all sources and for the etiologically or prognostically pertinent period.

Evidence supports the role of vitamin D in various conditions of development and ageing. Serum 25-hydroxyvitamin D (25(OH)D) is the best indicator for current vitamin D status. However, the cost of its measurement can be prohibitive in epidemiological research. We developed and validated multivariable regression models that quantified the relationships between vitamin D determinants, measured through an in-person interview, and serum 25(OH)D concentrations. A total of 200 controls participating in a population-based case–control study in Montreal, Canada, provided a blood specimen and completed an in-person interview on socio-demographic, reproductive, medical and lifestyle characteristics and personal attributes. Serum 25(OH)D concentrations were quantified by liquid chromatography–tandem MS. Multivariable least squares regression was used to build models that predict 25(OH)D concentrations from interview responses. We assessed high-order effects, performed sensitivity analysis using the lasso method and conducted cross-validation of the prediction models. Prediction models were built for users and non-users of vitamin D supplements separately. Among users, alcohol intake, outdoor time, sun protection, dose of supplement use, menopausal status and recent vacation were predictive of 25(OH)D concentrations. Among non-users, BMI, sun sensitivity, season and recent vacation were predictive of 25(OH)D concentrations. In cross-validation, 46–47 % of the variation in 25(OH)D concentrations were explained by these predictors. In the absence of 25(OH)D measures, our study supports that predicted 25(OH)D scores may be used to assign exposure in epidemiological studies that examine vitamin D exposure.

Introduction Il a été prouvé qu’un régime alimentaire de piètre qualité augmente le risque de maladies chroniques courantes susceptibles de nuire à la qualité de vie et d'alourdir le fardeau qui pèse sur le système de santé. Les recommandations fondées sur des données probantes du Guide alimentaire canadien (GAC) fournissent des conseils nutritionnels destinés à améliorer la qualité du régime alimentaire. L’Indice canadien de saine alimentation (ICSA), un outil de mesure de la qualité du régime alimentaire, permet d'évaluer la conformité au GAC. Le Questionnaire canadien de fréquence alimentaire II (QFA-C II) [Canadian Diet History Questionnaire II, C-DHQ II], mis au point récemment, pourrait quant à lui servir à estimer l’ICSA au sein de la population canadienne si on pouvait ajouter à sa base de données sur les éléments nutritifs les équivalents des groupes alimentaires (correspondant aux portions du GAC). Nous décrivons dans cet article des méthodes destinées à enrichir cette base de données sur les éléments nutritifs du QFA-C II en vue d’estimer l’ICSA. Méthodologie Nous avons créé des équivalents des groupes alimentaires à partir de données provenant de diverses bases de données sur les aliments et les éléments nutritifs, en particulier l’Enquête sur la santé dans les collectivités canadiennes, cycle 2.2 Nutrition de 2004. Nous avons ajouté ces variables à la base de données sur les éléments nutritifs du QFA-C II. Nous avons déterminé les scores de l’ICSA et avons effectué des analyses descriptives pour les participants qui ont répondu au QFA-C II dans le cadre d’une étude transversale canadienne. Résultats Le score moyen de l’ICSA dans notre échantillon de 446 adultes de 20 à 83 ans était de 64,4 (écart-type : 10,8). Les femmes, les non-fumeurs et les personnes ayant un niveau de scolarité supérieur au secondaire ont obtenu de manière statistiquement significative des notes plus élevées que les hommes, les fumeurs et les personnes détenant un diplôme d’études secondaires ou moins. Conclusion La possibilité d’évaluer l’ICSA à l’aide du QFA-C II facilite l’étude de la qualité du régime alimentaire et de l'état de santé de la population canadienne.

Poor diet quality has been shown to increase the risk of common chronic diseases that can negatively impact quality of life and burden the healthcare system. Canada's Food Guide evidence-based recommendations provide dietary guidance aimed at increasing diet quality. Compliance with Canada's Food Guide can be assessed with the Canadian Healthy Eating Index (C-HEI), a diet quality score. The recently designed Canadian Diet History Questionnaire II (C-DHQ II), a comprehensive food frequency questionnaire could be used to estimate the C-HEI in Canadian populations with the addition of food group equivalents (representing Canada's Food Guide servings) to the C-DHQ II nutrient database. We describe methods developed to augment the C-DHQ II nutrient database to estimate the C-HEI.Food group equivalents were created using food and nutrient data from existing published food and nutrient databases (e.g. the Canadian Community Health Survey - Cycle 2.2 Nutrition [2004]). The variables were then added to the C-DHQ II companion nutrient database. C-HEI scores were determined and descriptive analyses conducted for participants who completed the C-DHQ II in a cross-sectional Canadian study.The mean (standard deviation) C-HEI score in this sample of 446 adults aged 20 to 83 was 64.4 (10.8). Women, non-smokers, and those with more than high school education had statistically significant higher C-HEI scores than men, smokers and those with high school diplomas or less.The ability to assess C-HEI using the C-DHQ II facilitates the study of diet quality and health outcomes in Canada.Il a été prouvé qu’un régime alimentaire de piètre qualité augmente le risque de maladies chroniques courantes susceptibles de nuire à la qualité de vie et d'alourdir le fardeau qui pèse sur le système de santé. Les recommandations fondées sur des données probantes du Guide alimentaire canadien (GAC) fournissent des conseils nutritionnels destinés à améliorer la qualité du régime alimentaire. L’Indice canadien de saine alimentation (ICSA), un outil de mesure de la qualité du régime alimentaire, permet d'évaluer la conformité au GAC. Le Questionnaire canadien de fréquence alimentaire II (QFA-C II) [Canadian Diet History Questionnaire II, C-DHQ II], mis au point récemment, pourrait quant à lui servir à estimer l’ICSA au sein de la population canadienne si on pouvait ajouter à sa base de données sur les éléments nutritifs les équivalents des groupes alimentaires (correspondant aux portions du GAC). Nous décrivons dans cet article des méthodes destinées à enrichir cette base de données sur les éléments nutritifs du QFA-C II en vue d’estimer l’ICSA.Nous avons créé des équivalents des groupes alimentaires à partir de données provenant de diverses bases de données sur les aliments et les éléments nutritifs, en particulier l’Enquête sur la santé dans les collectivités canadiennes, cycle 2.2 Nutrition de 2004. Nous avons ajouté ces variables à la base de données sur les éléments nutritifs du QFA-C II. Nous avons déterminé les scores de l’ICSA et avons effectué des analyses descriptives pour les participants qui ont répondu au QFA-C II dans le cadre d’une étude transversale canadienne.Le score moyen de l’ICSA dans notre échantillon de 446 adultes de 20 à 83 ans était de 64,4 (écart-type : 10,8). Les femmes, les non-fumeurs et les personnes ayant un niveau de scolarité supérieur au secondaire ont obtenu de manière statistiquement significative des notes plus élevées que les hommes, les fumeurs et les personnes détenant un diplôme d’études secondaires ou moins.La possibilité d’évaluer l’ICSA à l’aide du QFA-C II facilite l’étude de la qualité du régime alimentaire et de l'état de santé de la population canadienne.

Many clinical features of lung cancer are different in women and men. Sex steroid hormones exert effects in nonreproductive organs, such as the lungs. The association between menstrual and childbearing factors and the risk of lung cancer among women is still debated. We performed a pooled analysis of eight studies contributing to the International Lung Cancer Consortium (4,386 cases and 4,177 controls). Pooled associations between menstrual or reproductive factors and lung cancer were estimated using multivariable unconditional logistic regression. Subgroup analyses were done for menopause status, smoking habits and histology. We found no strong support for an association of age at menarche and at menopause with lung cancer, but peri/postmenopausal women were at higher risk compared to premenopausal (OR 1.47, 95% CI 1.11-1.93). Premenopausal women showed increased risks associated with parity (OR 1.74, 95% CI 1.03-2.93) and number of children (OR 2.88, 95% CI 1.21-6.93 for more than 3 children; p for trend 0.01) and decreased with breastfeeding (OR 0.54, 95% CI 0.30-0.98). In contrast, peri/postmenopausal subjects had ORs around unity for the same exposures. No major effect modification was exerted by smoking status or cancer histology. Menstrual and reproductive factors may play a role in the genesis of lung cancer, yet the mechanisms are unclear, and smoking remains the most important modifiable risk factor. More investigations in large well-designed studies are needed to confirm these findings and to clarify the underlying mechanisms of gender differences in lung cancer risk.

We thank Drs. Morfeld and Erren for conveying their agreement of our consideration of chronoytpe as a potential effect modifier, and not as a potential confounder, in the relationship between shift work and ovarian cancer ([1][1]). Their proposition to consider chronodisruption as a single time

Background There is inadequate evidence to determine whether there is an effect of alcohol consumption on lung cancer risk. We conducted a pooled analysis of data from the International Lung Cancer Consortium and the SYNERGY study to investigate this possible association by type of beverage with adjustment for other potential confounders. Methods Twenty one case-control studies and one cohort study with alcohol-intake data obtained from questionnaires were included in this pooled analysis (19,149 cases and 362,340 controls). Adjusted odds ratios (OR) or hazard ratios (HR) with corresponding 95% confidence intervals (CI) were estimated for each measure of alcohol consumption. Effect estimates were combined using random or fixed-effects models where appropriate. Associations were examined for overall lung cancer and by histological type. Results We observed an inverse association between overall risk of lung cancer and consumption of alcoholic beverages compared to non-drinkers, but the association was not monotonic. The lowest risk was observed for persons who consumed 10–19.9 g/day ethanol (OR vs. non-drinkers = 0.78; 95% CI: 0.67, 0.91), where 1 drink is approximately 12–15 g. This J-shaped association was most prominent for squamous cell carcinoma (SCC). The association with all lung cancer varied little by type of alcoholic beverage, but there were notable differences for SCC. We observed an association with beer intake (OR for ≥20 g/day vs nondrinker = 1.42; 95% CI: 1.06, 1.90). Conclusions Whether the non-monotonic associations we observed or the positive association between beer drinking and squamous cell carcinoma reflect real effects await future analyses and insights about possible biological mechanisms.

Challenges and complexities associated with assessing dietary intakes are numerous, but not insurmountable. This opinion paper from Canadian researchers draws attention to the importance of building capacity and providing funding opportunities for research in dietary assessment methods in Canada and elsewhere. Such strategies would contribute to a better understanding of the roles played by diet in human health and better translation of this information into the most meaningful and effective dietary guidelines, policies, and interventions.

It has been hypothesized that, following a reduction in human papillomavirus (HPV) vaccine–targeted genotypes, an increase in prevalence of other HPV types may occur due to reduced competition during natural infection. Any apparent postvaccination increase must be distinguished from diagnostic artifacts consequent to consensus PCR assays failing to detect HPV types present in low copy numbers in coinfected specimens (under the assumption that with a drop in vaccine-preventable types there may be increased detection of previously “masked” types). We reanalyzed anogenital specimens to evaluate unmasking of HPV52 that may be caused by elimination of HPV16. Using highly sensitive type-specific real-time HPV52 PCR, we retested 1,200 anogenital specimens (all HPV52 negative according to consensus PCR assays) from six epidemiologic studies (200 specimens/study; 100 HPV16+/study). Multivariate logistic regression, with adjustment for age and number of sexual partners, was used to evaluate the association between HPV16 positivity and detection of HPV52. In our pooled analysis (n = 1,196), the presence of HPV16 was positively associated with HPV52 detection [adjusted OR, 1.47; 95% confidence interval (CI), 0.76–2.82]. In our separate (study specific) analyses, a statistically significant association was observed in one study that included HIV-infected males (HIPVIRG study; adjusted OR, 3.82; 95% CI, 1.19–12.26). We observed a positive association between HPV16 viral load (tertiles) and detection of HPV52 (P for trend = 0.003). These results indicate that diagnostic artifacts, resulting from unmasking of HPV52, may occur in some settings in the evaluation of HPV type replacement. Additional studies exploring the extent and severity of unmasking are needed. Cancer Epidemiol Biomarkers Prev; 24(1); 286–90. ©2014 AACR.

International audience; 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 (NCASES = 727; NCONTROLS = 1,351).; 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.; In both sexes, increasing recreational PA was associated with a lower lung cancer risk (ORMEN = 0.66, 95% confidence interval (CI) 0.47-0.92; ORWOMEN = 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 (ORMEN = 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.; 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.

International audience; While diets rich in fruit and vegetables appear to reduce lung cancer risk, the evidence for individual carotenoid and vitamin intakes has been judged too limited to reach firm conclusions. Data from a case-control study of lung cancer (Montreal, QC, Canada, 1996-2002) were used to investigate the role of dietary intakes of β-carotene, α-carotene, β-cryptoxanthin, lutein/zeaxanthin, lycopene, and vitamin C in lung cancer risk. In-person interviews elicited dietary information from 1,105 incident cases and 1,449 population controls. Usual frequency of consumption of 49 fruits and vegetables 2 years prior to diagnosis/interview was collected. Odds ratios (ORs) and 95% confidence intervals (CIs) between intake variables and lung cancer were estimated using logistic or polytomous regression, adjusting for potential confounding factors including a detailed smoking history. ORs associated with upper versus lower tertiles of intake were 0.66 (95% CI = 0.51-0.84) for β-carotene, 0.70 (95% CI = 0.55-0.90) for α-carotene, 0.65 (95% CI = 0.51-0.84) for β-cryptoxanthin, 0.75 (95% CI = 0.59-0.95) for lycopene, and 0.74 (95% CI = 0.58-0.96) for vitamin C. ORs suggestive of a protective effect were found for elevated intakes of β-carotene, α-carotene, β-cryptoxanthin, and lycopene in male heavy smokers and of vitamin C in female heavy smokers. Selected antioxidants were also associated with a lower risk of lung cancer in female moderate smokers, and of squamous cell carcinoma, adenocarcinoma, and small cell carcinoma. These results suggest that several dietary antioxidants found in common food sources may protect against lung cancer, even among heavy smokers.

Advances in technology-enabled dietary assessment include the advent of web-based food frequency questionnaires, which may reduce costs and researcher burden but may introduce new challenges related to internet connectivity and computer literacy. The purpose of this study was to evaluate the intra- and inter-version reliability, feasibility and acceptability of the paper and web Canadian Diet History Questionnaire II (CDHQ-II) in a sub-sample of 648 adults (aged 39-81 years) recruited from Alberta's Tomorrow Project. Participants were randomly assigned to one of two groups: (1) paper, web, paper; or (2) web, paper, web over a six-week period. With few exceptions, no statistically significant differences in mean nutrient intake were found in the intra- and inter-version reliability analyses. The majority of participants indicated future willingness to complete the CDHQ-II online, and 59% indicated a preference for the web over the paper version. Findings indicate that, in this population of adults drawn from an existing cohort, the CDHQ-II may be administered in paper or web modalities (increasing flexibility for questionnaire delivery), and the nutrient estimates obtained with either version are comparable. We recommend that other studies explore the feasibility and reliability of different modes of administration of dietary assessment instruments prior to widespread implementation.

Methylation of human papillomavirus (HPV) and host genes may predict cervical cancer risk. We examined the methylation status of selected sites in HPV16 and human genes in DNA extracted from exfoliated cervical cell samples of 244 women harboring HPV16-positive cancer or cervical intraepithelial neoplasia (CIN) or negative for intraepithelial lesions or malignancy (NILM). We quantified the methylation of CpG sites in the HPV16 L1 gene (CpG 6367 and 6389) and in the human genes EPB41L3 (CpG 438, 427, 425) and LMX1 (CpG 260, 262, 266, 274) following bisulfite treatment and pyrosequencing. Receiver operating characteristic (ROC) curves were used to analyze the diagnostic utility of methylation level for the different sites and for a joint predictor score. Methylation in all sites significantly increased with lesion severity (p

Background The genomic diversity of high-risk human papillomaviruses (HPV) has been associated with viral persistence and HPV-induced lesions. Studies on HPV56 persistence are still pending. Objective To assess the association between HPV56 polymorphism and HPV56 persistence and presence of high-grade cervical intraepithelial neoplasia (CIN2,3) or cancer. Study design HPV56-positive cervical specimens from 204 women selected from a total of 4669 participants recruited in 5 epidemiological studies (parent studies) were further analyzed by PCR-sequencing of the long control region (LCR). Results Of the 81 women followed prospectively in cohort studies who could be classified, 34 had persistent and 47 had transient HPV56 infections. Variant HPV56-LCR-MTL-21 was detected more frequently in persistent infections (52.9%, 95% CI: 36.7–68.6%) than in transient infections (25.5%, 95% CI: 15.1–39.4). Considering only women recruited in a cohort of women infected or at high risk for HIV infection, infection with variant HPV56-LCR-MTL-21 (OR = 4.4, 95% CI: 1.3–14.5) was significantly associated with HPV56 persistence controlling in multivariate analysis for high risk HPV detection and HIV infection. A variation at nucleotide 7800 in HPV56-LCR-MTL-21 resulted in the loss of a binding site for Elf-1 embedded in one of the E2 binding sites, a potential activator or repressor of expression of the HPV genome. HPV56 polymorphism was not associated with CIN2,3 or cancer in women enrolled in cross-sectional and case–control studies. Conclusion Polymorphism in HPV56 may influence the risk that infections with this type will persist.

Female sex workers are at high risk for HIV infection. Sexually transmitted infections are known to be co-factors for HIV infection. Our aims were (1) to assess the prevalence of HIV and other sexually transmitted infections in this population; (2) to determine the association between sociodemographic characteristics, behavioural variables, and variables related to HIV prevention and HIV infection. A cross-sectional study was conducted in Conakry, Guinea, among a convenience sample of 223 female sex workers. A questionnaire on sociodemographic characteristics, risk factors, and exposure to prevention was administered. Screening for HIV, herpes simplex virus type 2, human papillomavirus type 16, Neisseria gonorrhoeae, and Chlamydia trachomatis was performed. Prevalences of HIV, herpes simplex virus type 2, human papillomavirus type 16, N. gonorrhoeae, and C. trachomatis were 35.3%, 84.1%, 12.2%, 9.0%, and 13.6%, respectively. Having a child, lubricant use, and human papillomavirus type 16 infection were associated with HIV infection. Interventions that promote screening and treatment of sexually transmitted infections are needed in order to achieve successful interventions to prevent HIV among female sex workers in resource-limited settings.

BACKGROUND: Interventions for condom use promotion have been undertaken for HIV prevention among female sex workers (FSWs). Our aims are to (1) assess the frequency of inconsistent condom use with clients and with the main regular non-client sex partner (RNCP); and (2) investigate factors associated with inconsistent condom use with the RNCP particularly the desire to have children and links of the RNCP with commercial sex work. METHODS: A cross-sectional study was conducted in Conakry Guinea among 223 FSWs. A questionnaire on socio-demographic characteristics behaviours and desire for children was administered. Descriptive statistics and logistic regression were performed. RESULTS: Inconsistent condom use was frequent with the RNCP but rare with the clients (80.4% vs. 1.3%). FSWs desire for children was strongly associated with inconsistent condom use with the RNCP. CONCLUSION: Interventions that take into account reproductive health are needed to prevent HIV among FSWs and their children.

There is as yet no generally accepted explanation for the common finding that low body mass index (BMI) is associated with an increased risk of lung cancer. We investigated this association in a Canadian population-based case–control study (1996–2002) with a particular view to assessing the hypothesis that the observed association was due to residual confounding by smoking. Analyses were based on 1,076 cases and 1,439 controls who provided their height at enrollment and their weight at two points in time, at age 20 and 2 years before enrollment. BMI, in kg/m2, was classified into underweight (

It is not clear whether alcohol consumption is associated with lung cancer risk. The relationship is likely confounded by smoking, complicating the interpretation of previous studies. We examined the association of alcohol consumption and lung cancer risk in a large pooled international sample, minimizing potential confounding of tobacco consumption by restricting analyses to never smokers. Our study included 22 case-control and cohort studies with a total of 2548 never-smoking lung cancer patients and 9362 never-smoking controls from North America, Europe and Asia within the International Lung Cancer Consortium (ILCCO) and SYNERGY Consortium. Alcohol consumption was categorized into amounts consumed (grams per day) and also modelled as a continuous variable using restricted cubic splines for potential non-linearity. Analyses by histologic sub-type were included. Associations by type of alcohol consumed (wine, beer and liquor) were also investigated. Alcohol consumption was inversely associated with lung cancer risk with evidence most strongly supporting lower risk for light and moderate drinkers relative to non-drinkers (>0-4.9 g per day: OR = 0.80, 95% CI = 0.70-0.90; 5-9.9 g per day: OR = 0.82, 95% CI = 0.69-0.99; 10-19.9 g per day: OR = 0.79, 95% CI = 0.65-0.96). Inverse associations were found for consumption of wine and liquor, but not beer. The results indicate that alcohol consumption is inversely associated with lung cancer risk, particularly among subjects with low to moderate consumption levels, and among wine and liquor drinkers, but not beer drinkers. Although our results should have no relevant bias from the confounding effect of smoking we cannot preclude that confounding by other factors contributed to the observed associations. Confounding in relation to the non-drinker reference category may be of particular importance.

Many clinical features of lung cancer are different in women and men. Sex steroid hormones exert effects in non-reproductive organs, such as the lungs. The association between menstrual and childbearing factors and the risk of lung cancer among women is still debated. We performed a pooled analysis of eight studies contributing to the International Lung Cancer Consortium (ILCCO; 4,386 cases and 4,177 controls). Pooled associations between menstrual or reproductive factors and lung cancer were estimated using multivariable unconditional logistic regression. Subgroup analyses were done for menopause status, smoking habits and histology. We found no strong support for an association of age at menarche and at menopause with lung cancer, but peri/postmenopausal women were at higher risk compared to premenopausal (OR 1.47, 95% CI 1.11–1.93). Premenopausal women showed increased risks associated with parity (OR 1.74, 95% CI 1.03–2.93) and number of children (OR 2.88 95% CI 1.21–6.93 for more than 3 children; P for trend 0.01) and decreased with breastfeeding (OR 0.54, 95% CI 0.30–0.98). In contrast, peri/postmenopausal subjects had ORs around unity for the same exposures. No major effect modification was exerted by smoking status or cancer histology. Menstrual and reproductive factors may play a role in the genesis of lung cancer, yet the mechanisms are unclear, and smoking remains the most important modifiable risk factor. More investigations in large well-designed studies are needed to confirm these findings and to clarify the underlying mechanisms of gender differences in lung cancer risk.

International audience; Hormone-related factors have been associated with ovarian cancer, the strongest being parity and oral contraceptive use. Given reductions in birth rates and increases in oral contraceptive use over time, associations in more recent birth cohorts may differ. Furthermore, consideration of ovarian cancer heterogeneity (i.e., Type I/II invasive cancers) may contribute to a better understanding of etiology. We examined hormone-related factors in relation to ovarian cancer risk overall, for Type I and Type II cancers, as well as borderline tumors.; A population-based case-control study was carried out in Montreal, Canada from 2011 to 2016, including 496 cases and 908 controls. For each hormone-related variable, adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression for ovarian cancer overall, and using polytomous logistic regression for associations by tumor behavior and ovarian cancer type.; Parity was inversely associated with risk overall and by tumor behavior and type, with a stronger OR (95% CI) for Type I [0.09 (0.04-0.24) for ≥3 full-term births vs. nulliparity] vs. Type II [0.66 (0.43-1.02)] invasive cancers; the OR (95% CI) for borderline tumors was 0.41 (0.22-0.77). Oral contraceptive ever use was not associated with risk overall, but ≥10 years of use vs. never use reduced risk, particularly for invasive cancers. A history of endometriosis was most strongly associated with Type I cancers. Associations with other factors were less clear.; These results suggest that associations with some hormone-related factors may differ between borderline and invasive Type I and II ovarian cancers.

Introduction Globally, brain cancer is responsible for an estimated 189 000 deaths annually and is also associated with substantial morbidity and cost. Prevention of brain cancer is particularly important since treatment is often ineffective; however, little is known regarding the aetiology of this disease. Metals and metalloids are potential carcinogens to which millions of workers worldwide are exposed daily. They may accumulate in the brain and thus contribute to brain cancer development. Methodology The INTEROCC study is a multi-centre case-control study on the association between occupational carcinogens and brain cancer, which included 2054 glioma cases, 1924 meningioma cases, and 5601 controls aged ≥18 years old. Lifetime occupational exposure to mercury, lead, cadmium, zinc, chromium, iron, nickel, calcium, silicon, and welding fumes was estimated using lifetime occupational histories and the Canadian Job-Exposure Matrix (CANJEM). For each agent, a binary never/ever exposure variable was created, where ever exposed was defined as having ever held an occupation for ≥1 year with a probability of exposure of ≥25%. Analyses were conducted for glioma and meningioma risk separately. Multivariate odds ratios and 95% confidence intervals for the associations between ever exposure to the selected occupational agents and risk were estimated using conditional logistic regression by combining the data from all study centres, conditioning on study centre, sex, and age (5-year group), and adjusting for covariates. Results We observed no evidence of associations between ever occupational exposure to metals and metalloids and glioma. Ever occupational exposure to cadmium, zinc, chromium, nickel and silicon were positively associated with meningioma, with ORs ranging from 1.26 to 1.52, which were statistically significant for zinc, nickel, and silicon. All remaining associations were near the null value. Conclusion Occupational exposure to some of the selected agents was positively associated with meningioma, but not glioma.

ObjectiveTo evaluate the Canadian Diet History Questionnaire I (C-DHQ I) food list and to adapt the US DHQ II for Canada using Canadian dietary survey data.DesignTwenty-four-hour dietary recalls reported by adults in a national Canadian survey were analysed to create a food list corresponding to C-DHQ I food questions. The percentage contribution of the food list to the total survey intake of seventeen nutrients was used as the criterion to evaluate the suitability of the C-DHQ I to capture food intake in Canadian populations. The data were also analysed to identify foods and to modify portion sizes for the C-DHQ II.SettingThe Canadian Community Health Survey (CCHS) – Cycle 2.2 Nutrition (2004).SubjectsAdults (n20 159) who completed 24 h dietary recalls during in-person interviews.ResultsFour thousand five hundred and thirty-three foods and recipes were grouped into 268 Food Groups, of which 212 corresponded to questions on the C-DHQ I. Nutrient intakes captured by the C-DHQ I ranged from 79 % for fat to 100 % for alcohol. For the new C-DHQ II, some food questions were retained from the original US DHQ II while others were added based on foods reported in CCHS and foods available on the Canadian market since 2004. Of 153 questions, 143 were associated with portion sizes of which fifty-three were modified from US values. Sex-specific nutrient profiles for the C-DHQ II nutrient database were derived using CCHS data.ConclusionsThe C-DHQ I and II are designed to optimize the capture of foods consumed by Canadian populations.

Purpose Coffee and black tea are among the most consumed beverages worldwide. Although their potential role in lung cancer occurrence has been investigated in several studies, results have been inconclusive. We investigated the associations between intake of coffee and black tea with lung cancer in a population-based case–control study in Montreal, Canada. Methods These analyses included 1130 cases and 1483 controls. Adjusted odds ratios (ORs) were estimated between four metrics of coffee and black tea consumption (frequency, average daily amount, duration, and cumulative amount) and lung cancer, using unconditional logistic regression. Results The adjusted ORs (95% confidence intervals) for lung cancer comparing daily to never consumers were 0.73 (0.49–1.10) for coffee and 1.05 (0.85–1.31) for black tea. Analyses of other metrics did not reveal any clear patterns of increasing or decreasing risk with increasing amounts or duration of consumption. There was no strong evidence of OR modification by sex or smoking level. The OR estimates did not materially differ by histological subtype for either of the beverages. Conclusion Our results do not provide strong support for associations between consumption of coffee and black tea and lung cancer.

Need careful diagnostic evaluation “How worried should I be?” is what women often ask when told that their screening cervical cytology result is abnormal. Unfortunately, when the result indicates atypical glandular cells (AGC), it is difficult to answer this question with certainty. The study by Wang and colleagues,1 assessing the short and long term risk of cervical cancer after detection of AGC from cervical smear tests in Sweden, provides useful information. The team examined the risk of cervical cancer up to 15 years after a first finding of AGC in a cohort of over three million women. The large sample makes it possible to provide precise estimates of risk following this rare diagnostic category. Glandular pathologies are difficult to diagnose and may be under-ascertained in the short term, making studies with longitudinal assessment and minimal losses to follow-up essential. The fact …

The association between polymorphism of human papillomavirus type 52 (HPV52) and high-grade cervical intraepithelial neoplasia (CIN2,3) was investigated in Canadian women. HPV-52-positive endocervical specimens collected from 216 women selected from a total of 3,614 participants recruited in two case-control and two cohort studies conducted in Canada, were further analyzed by PCR-sequencing of the LCR and E6 gene. Overall, the HPV52 LCR prototype was detected more frequently in Caucasian women (69 of 132, 52.3%, 95% confidence interval (CI): 43.8%-60.6%) than in non-Caucasian women (15 of 48, 31.3%, 95% CI 19.9%-45.4%). In two cohort studies, HPV52 prototype was detected in seven of 15 (46.7%, 95% CI 24.8-69.9) HPV52 persistent infections and 14 of 35 (40.0%, 95% CI 25.5-56.5) transient infections (p = 0.76). In two case-control studies, 30 participants did not have CIN, 18 had low-grade CIN (CIN1), 64 had CIN2,3, seven had cervical cancer and the diagnosis was undefined for 27 women. Variant MTL-52-LCR-02 was detected more frequently in women with cancer (28.6%, 95% CI 7.6%-64.8%) than in women without cancer or CIN2,3 (0%, 95% CI 0.0%-9.2%; p = 0.015). CIN2,3 risk was significantly associated with a deletion at nucleotide position 7695 in the LCR (OR 4.9, 95% CI 1.2-20.8), the T7744C variation in the LCR (OR 5.7, 95% CI 1.1-32.0), and the K93R variation in E6 (OR 6.9, 95% CI 1.3-36.8), after adjusting for age, detection of HPV16 or 18 and study site. These findings indicate that HPV52 polymorphism influences risk of CIN-2,3 and possibly invasive cancer.

Human leukocyte antigen (HLA)-G acts as negative regulator of the immune responses and its expression in tumor cells may enable them to escape immunosurveillance. The purpose of this study was to investigate the influence of HLA-G polymorphism on risk of high-grade cervical intraepithelial neoplasia (HG-CIN) and cervical cancer in a Canadian population. The authors have analyzed 1,372 women from participants recruited between 2001 and 2009 in the ongoing Biomarkers of Cervical Cancer Risk case–control study. A total of 539 women with histologically confirmed HG-CIN and invasive cancer formed the case series, and 833 women with normal cytology served as controls. Cervical specimens were tested for human papillomavirus (HPV) DNA using the MY09/11 PCR protocol and HLA-G alleles where determined using a direct DNA sequencing procedures. HLA-G polymorphisms were not associated with HG-CIN or HPV infection. However, the risk for invasive cancer was significantly increased with the homozygous genotypes HLA-G*01:01:02 [odds ratio (OR) = 3.52, 95% confidence interval (CI): 1.43–8.61, p = 0.006], −G*01:06 (OR = 19.1, 95% CI: 2.29–159, p = 0.005) and −G* 3′UTR 14-bp insertion (OR = 2.17, 95% CI: 1.10–4.27, p = 0.020), whereas, the heterozygotic form of the G*01:01:01 wild-type allele was significantly associated with a reduced risk of invasive cancer (OR = 0.31, 95% CI: 0.16–0.59, p < 0.0001) after adjusting for age, HPV infection and ethnicity. These associations were also observed with progression of disease from HG-CIN to invasive cancer among HPV-positive women. These results suggest that HLA-G polymorphism is an independent risk factor for the development of invasive cervical cancer.

Background The association between human papillomavirus (HPV) viral load and high-grade squamous intraepithelial lesion (HSIL) of the uterine cervix has been demonstrated for high-risk HPV-16 but has not been investigated for low-risk HPV types. Objective To determine the association between the presence of low-grade SIL (LSIL) and viral load of low-risk HPV type 6. Study design 107 HPV-6-positive cytobrush samples collected from 90 women (67 without SIL, 11 with LSIL, 5 with HSIL, 6 with SIL of unknown grade and 1 with a smear with LSIL and a normal colposcopy) were analyzed for their content of HPV-6 DNA. Methods HPV-6 E6 and E2 DNA loads were measured in the cytobrush samples with two real-time PCR assays. HPV-6 integration was confirmed with restriction-site PCR. Results HPV-6 DNA in cervical samples ranged from 1.8 × 10 2 to 4.25 × 10 8 copies per μg of cellular DNA. HPV-6 E6 DNA loads were higher in women with LSIL, with or without co-infection with high-risk HPV types, than in women without SIL ( p = 0.03). HPV-6 loads greater than 8.76 × 10 6 copies per μg DNA, corresponding to the mean HPV-6 load measured in women with LSIL, were more frequently detected in these women with LSIL than in women without LSIL, controlling for age (odds ratio 13.5, 95% confidence interval 1.1–172.4). Although 10 samples generated HPV-6 E6/E2 ratios above 2, there was no evidence of integration of HPV-6 by restriction-site PCR. Conclusion Samples from women with LSIL contained higher HPV-6 loads than women without SIL. HPV-6 DNA was not integrated into cellular DNA in these samples.