BackgroundAn association between low socioeconomic status (SES) and lung cancer has been observed in several studies, but often without adequate control for smoking behavior. We studied the association between lung cancer and occupationally derived SES, using data from the international pooled SYNERGY study.MethodsTwelve case-control studies from Europe and Canada were included in the analysis. Based on occupational histories of study participants we measured SES using the International Socio-Economic Index of Occupational Status (ISEI) and the European Socio-economic Classification (ESeC). We divided the ISEI range into categories, using various criteria. Stratifying by gender, we calculated odds ratios (OR) and 95% confidence intervals (CI) by unconditional logistic regression, adjusting for age, study, and smoking behavior. We conducted analyses by histological subtypes of lung cancer and subgroup analyses by study region, birth cohort, education and occupational exposure to known lung carcinogens.ResultsThe analysis dataset included 17,021 cases and 20,885 controls. There was a strong elevated OR between lung cancer and low SES, which was attenuated substantially after adjustment for smoking, however a social gradient persisted. SES differences in lung cancer risk were higher among men (lowest vs. highest SES category: ISEI OR 1.84 (95% CI 1.61–2.09); ESeC OR 1.53 (95% CI 1.44–1.63)), than among women (lowest vs. highest SES category: ISEI OR 1.54 (95% CI 1.20–1.98); ESeC OR 1.34 (95% CI 1.19–1.52)).ConclusionSES remained a risk factor for lung cancer after adjustment for smoking behavior.

BackgroundThe nature of the association between occupational social prestige, social mobility, and risk of lung cancer remains uncertain. Using data from the international pooled SYNERGY case–control study, we studied the association between lung cancer and the level of time-weighted average occupational social prestige as well as its lifetime trajectory.MethodsWe included 11,433 male cases and 14,147 male control subjects. Each job was translated into an occupational social prestige score by applying Treiman’s Standard International Occupational Prestige Scale (SIOPS). SIOPS scores were categorized as low, medium, and high prestige (reference). We calculated odds ratios (OR) with 95 % confidence intervals (CI), adjusting for study center, age, smoking, ever employment in a job with known lung carcinogen exposure, and education. Trajectories in SIOPS categories from first to last and first to longest job were defined as consistent, downward, or upward. We conducted several subgroup and sensitivity analyses to assess the robustness of our results.ResultsWe observed increased lung cancer risk estimates for men with medium (OR = 1.23; 95 % CI 1.13–1.33) and low occupational prestige (OR = 1.44; 95 % CI 1.32–1.57). Although adjustment for smoking and education reduced the associations between occupational prestige and lung cancer, they did not explain the association entirely. Traditional occupational exposures reduced the associations only slightly. We observed small associations with downward prestige trajectories, with ORs of 1.13, 95 % CI 0.88–1.46 for high to low, and 1.24; 95 % CI 1.08–1.41 for medium to low trajectories.ConclusionsOur results indicate that occupational prestige is independently associated with lung cancer among men.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2432-9) contains supplementary material, which is available to authorized users.

Urothelial cancer (UCa) is the most predominant cancer of the urinary tract and noninvasive diagnosis using hypermethylation signatures in urinary cells is promising. Here, we assess gender differences in a newly identified set of methylation biomarkers. UCa‐associated hypermethylated sites were identified in urine of a male screening cohort (n = 24) applying Infinium‐450K‐methylation arrays and verified in two separate mixed‐gender study groups (n = 617 in total) using mass spectrometry as an independent technique. Additionally, tissue samples (n = 56) of mixed‐gender UCa and urological controls (UCt) were analyzed. The hypermethylation signature of UCa in urine was specific and sensitive across all stages and grades of UCa and independent on hematuria. Individual CpG sensitivities reached up to 81.3% at 95% specificity. Albeit similar methylation differences in tissue of both genders, differences were less pronounced in urine from women, most likely due to the frequent presence of squamous epithelial cells and leukocytes. Increased repression of methylation levels was observed at leukocyte counts ≥500/μl urine which was apparent in 30% of female and 7% of male UCa cases, further confirming the significance of the relative amounts of cancerous and noncancerous cells in urine. Our study shows that gender difference is a most relevant issue when evaluating the performance of urinary biomarkers in cancer diagnostics. In case of UCa, the clinical benefits of methylation signatures to male patients may outweigh those in females due to the general composition of women's urine. Accordingly, these markers offer a diagnostic option specifically in males to decrease the number of invasive cystoscopies.

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Here, we discovered TGFBI as a new urinary biomarker for muscle invasive and high-grade urothelial carcinoma (UC). After biomarker identification using antibody arrays, results were verified in urine samples from a study population consisting of 303 patients with UC, and 128 urological and 58 population controls. The analyses of possible modifying factors (age, sex, smoking status, urinary leukocytes and erythrocytes, and history of UC) were calculated by multiple logistic regression. Additionally, we performed knockdown experiments with TGFBI siRNA in bladder cancer cells and investigated the effects on proliferation and migration by wound closure assays and BrdU cell cycle analysis. TGFBI concentrations in urine are generally increased in patients with UC when compared to urological and population controls (1321.0 versus 701.3 and 475.6 pg/mg creatinine, respectively). However, significantly increased TGFBI was predominantly found in muscle invasive (14,411.7 pg/mg creatinine), high-grade (8190.7 pg/mg) and de novo UC (1856.7 pg/mg; all p < 0.0001). Knockdown experiments in vitro led to a significant decline of cell proliferation and migration. In summary, our results suggest a critical role of TGFBI in UC tumorigenesis and particularly in high-risk UC patients with poor prognosis and an elevated risk of progression on the molecular level.

Information on biomarkers of urothelial carcinomas (UC) for clinical decision-making is limited. Here, we newly identified and verified CXCL16 as a promising novel biomarker in urine for high grade and muscle invasive UC in a cross-sectional cohort of 308 UC patients, 126 urological hospital controls, and 50 population controls using antibody arrays and ELISA. Median CXCL16 levels in urine was significantly higher in UC patients (273.2 pg/mg creatinine) compared to hospital (148.1 pg/mg) and population controls (85.1 pg/mg) with a particular preference for high grade (460.8 pg/mg), muscle invasive (535.7 pg/mg) and primary UC (327.8 pg/mg) (all p<0.0001). Group differences were confirmed after adjusting or stratifying for potential clinical and individual characteristics, such as leukocyte counts, haematuria, age, gender, and smoking status. In contrast, CXCL16 showed less discriminating power in low grade (244.3 pg/mg), non-muscle invasive (≤pT1, 251.2 pg/mg) and recurrent UC (203.9 pg/mg). In agreement with its function in immune defence, expression of CXCL16 in tissue samples of primary UC patients (n=53) showed only a weak or no immunoreactivity compared to urological hospital controls (n=32). Expression of CXCR6, the G-protein-coupled receptor of CXCL16, remained unchanged. Our findings suggest that evading the immune defence by shedding cell-surface CXCL16 and its increased elimination in urine is a molecular feature of high grade and muscle invasive UC. Therefore, urinary CXCL16 may serve as a useful, simple and non-invasive tool to identify high-risk UC with increased risk of progression at the molecular level.

BackgroundAssociations of socioeconomic status (SES) and smoking-related diseases depend on uniform validity of self-reported smoking habits in different SES groups. We investigated the influence of SES on validity of self-reported smoking status by means of urinary cotinine.MethodsWe determined total urinary cotinine in the baseline population of the Heinz Nixdorf Recall Study. Participants with cotinine>200 µg/L were potential current smokers. We defined upper and lower 20% of the gender-specific distribution of the International Socio-Economic Index (ISEI) as high and low SES, respectively, else as intermediate. We analysed the association of self-reported smoking status and cotinine by ISEI and additional SES measures, stratified by gender. In self-reported non-smokers, we estimated age-adjusted ORs with 95% CI to detect differences by SES in the validity of self-reported smoking status.ResultsIn 2004 men and 1887 women, 78% and 80%, respectively, reported to be non-smokers. Median cotinine concentrations were 2 µg/L in non-smokers, and 3651 µg/L in male and 3127 µg/L in female smokers. Based on cotinine in non-smokers, 2.0 % of men (n = 32) and 1.8 % of women (n = 27) were potential smokers, with lower proportions in the subgroup of never-smokers (men: 0.7%, women: 0.5%). The validity of self-reported smoking status did not substantially differ by SES. Tendencies for increased underreporting were indicated for women with low ISEI (OR 1.35; 95% CI 0.54 to 3.39) and men in blue-collar jobs (OR 1.39; 95% CI 0.67 to 2.87).ConclusionValidity of self-reported smoking status in this elderly German cohort was high and did not depend on SES.

BackgroundThe association between socioeconomic disadvantage (low education and/or income) and head and neck cancer is well established, with smoking and alcohol consumption explaining up to three-quarters of the risk. We aimed to investigate the nature of and explanations for head and neck cancer risk associated with occupational socioeconomic prestige (a perceptual measure of psychosocial status), occupational socioeconomic position and manual-work experience, and to assess the potential explanatory role of occupational exposures.MethodsPooled analysis included 5818 patients with head and neck cancer (and 7326 control participants) from five studies in Europe and South America. Lifetime job histories were coded to: (1) occupational social prestige—Treiman’s Standard International Occupational Prestige Scale (SIOPS); (2) occupational socioeconomic position—International Socio-Economic Index (ISEI); and (3) manual/non-manual jobs.ResultsFor the longest held job, adjusting for smoking, alcohol and nature of occupation, increased head and neck cancer risk estimates were observed for low SIOPS OR=1.88 (95% CI: 1.64 to 2.17), low ISEI OR=1.74 (95% CI: 1.51 to 1.99) and manual occupations OR=1.49 (95% CI: 1.35 to 1.64). Following mutual adjustment by socioeconomic exposures, risk associated with low SIOPS remained OR=1.59 (95% CI: 1.30 to 1.94).ConclusionsThese findings indicate that low occupational socioeconomic prestige, position and manual work are associated with head and neck cancer, and such risks are only partly explained by smoking, alcohol and occupational exposures. Perceptual occupational psychosocial status (SIOPS) appears to be the strongest socioeconomic factor, relative to socioeconomic position and manual/non-manual work.