Sylvie Cénée

Relation between inducibility of CYP1A1, GSTM1 and lung cancer in a French population.

Smoking is the principal cause of lung cancer. However, not all smokers will develop this disease. Individual susceptibility to chemically induced cancer may be explained in part by genetic differences in the activation and detoxification of procarcinogens. The activation phase of polycyclic aromatic hydrocarbon (PAH) metabolism is governed by the enzyme CYP1A1, induced by PAH when it enters the body. The extent to which PAH induces CYP1A1 activity varies greatly from one subject to another. CYP1A1 inducibility has long been associated, although inconsistently, with an increased risk of lung cancer. In 1982, Kouri corroborated Kellermans results with a new method for measuring inducibility, but few studies have reported using this method. The glutathione S-transferases (GSTs) are involved in the detoxification phase of PAH, and the allelic deletion of GSTM1 has been also associated with an increased risk of lung cancer. We conducted a case-control study to examine the risk of lung cancer related, separately and together, to CYP1A1 inducibility, GSTM1 polymorphism and cigarette smoking in a French population. The 611 subjects were 310 incident lung cancer cases and 301 hospital control subjects. We were able to constitute a DNA bank for 552 subjects (89.5%) and gather detailed information on smoking history for all of them. Inducibility could be measured for 195 cases and 183 control subjects. Results for GSTM1 polymorphism concern 247 cases and 254 control subjects. GSTM1 polymorphism and inducibility could both be assessed for 179 cases and 166 control subjects. The odds ratio related to inducibility was 1.7 [1.0-3.0] for medium and 3.1 (1.3-7.4) for hyper inducers. The association with GSTM1 was 1.6 (1.0-2.6). With a reference category of subjects who were both low inducers and GSTM1(+), we found an odds ratio for lung cancer of 8.1 (2-31) for the subjects with both risk factors [i.e. GSTM1(-) and hyper inducers]. Our data did not reveal evidence of interaction between smoking and inducibility. On the other hand, we found an interaction of 3.6 (0.6-21) between inducibility and GSTM1.

Welding, a risk factor of lung cancer: the ICARE study

Objectives We investigated the relationship between lung cancer and occupational exposure to welding activity in ICARE, a population-based case–control study. Methods Analyses were restricted to men (2276 cases, 2780 controls). Welding exposure was assessed through detailed questionnaires, including lifelong occupational history. ORs were computed using unconditional logistic regression, adjusted for lifelong cigarette smoking and occupational exposure to asbestos. Results Among the regular welders, welding was associated with a risk of lung cancer (OR=1.7, 95% CI 1.1 to 2.5), which increased with the duration (OR=2.0, 95% CI 1.0 to 3.9 when duration >10u2005years), and was maximum 10–20u2005years since last welding. The risk was more pronounced in case of gas welding (OR=2.0, 95% CI 1.2 to 3.3), when the workpiece was covered by paint, grease, or other substances (OR=2.0, 95% CI 1.2 to 3.4) and when it was cleaned with chemical substances before welding. No statistically significant increase in lung cancer risk was observed among occasional welders. Conclusions Although these results should be confirmed, we showed that type of welding and mode of workpiece preparation are important determinants of the lung cancer risk in regular welders.

Multidimensional analysis of the effect of occupational exposure to organic solvents on lung cancer risk: the ICARE study

Background The association between lung cancer and occupational exposure to organic solvents is discussed. Since different solvents are often used simultaneously, it is difficult to assess the role of individual substances. Objectives The present study is focused on an in-depth investigation of the potential association between lung cancer risk and occupational exposure to a large group of organic solvents, taking into account the well-known risk factors for lung cancer, tobacco smoking and occupational exposure to asbestos. Methods We analysed data from the Investigation of occupational and environmental causes of respiratory cancers (ICARE) study, a large French population-based case–control study, set up between 2001 and 2007. A total of 2276 male cases and 2780 male controls were interviewed, and long-life occupational history was collected. In order to overcome the analytical difficulties created by multiple correlated exposures, we carried out a novel type of analysis based on Bayesian profile regression. Results After analysis with conventional logistic regression methods, none of the 11 solvents examined were associated with lung cancer risk. Through a profile regression approach, we did not observe any significant association between solvent exposure and lung cancer. However, we identified clusters at high risk that are related to occupations known to be at risk of developing lung cancer, such as painters. Conclusions Organic solvents do not appear to be substantial contributors to the occupational risk of lung cancer for the occupations known to be at risk.

Nonsteroidal anti-inflammatory drugs (NSAIDs) and prostate cancer risk: results from the EPICAP study

Chronic inflammation may play a role in prostate cancer carcinogenesis. In that context, our objective was to investigate the role of nonsteroidal anti‐inflammatory drugs (NSAIDs) in prostate cancer risk based on the EPICAP data. EPICAP is a population‐based case–control study carried out in 2012–2013 (département of Hérault, France) that enrolled 819 men aged less than 75 years old newly diagnosed for prostate cancer and 879 controls frequency matched to the cases on age. Face to face interviews gathered information on several potential risk factors including NSAIDs use. Odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated using unconditional logistic regression models. All‐NSAIDs use was inversely associated with prostate cancer: OR 0.77, 95% CI 0.61–0.98, especially in men using NSAIDs that preferentially inhibit COX‐2 activity (OR 0.48, 95% CI 0.28–0.79). Nonaspirin NSAIDs users had a decreased risk of prostate cancer (OR 0.72, 95% CI 0.53–0.99), particularly among men with an aggressive prostate cancer (OR 0.49, 95% CI 0.27–0.89) and in men with a personal history of prostatitis (OR 0.21, 95% CI 0.07–0.59). Our results are in favor of a decreased risk of prostate cancer in men using NSAIDs, particularly for men using preferential anti‐COX‐2 activity. The protective effect of NSAIDs seems to be more pronounced in aggressive prostate cancer and in men with a personal history of prostatitis, but this needs further investigations to be confirmed.

Professional Cleaning Activities and Lung Cancer Risk Among Women: Results From the ICARE Study.

Objectives: Lung cancer risk associated with occupational cleaning activities has been investigated in the population-based case–control study ICARE. Methods: Occupational history was collected by standardized interviews. Jobs were first defined according to the International Standard Classification of Occupations (ISCO) codes and then categorized according to activity sectors. Adjusted odds ratios (ORs) were estimated by unconditional logistic regression, separately for women (619 cases and 760 controls) and men (2265 and 2780). Results: Thirty percent of women and 2.3% of men controls ever held a cleaner or care job. Women who worked as housemaids longer than 7 years showed an OR of 1.76 [95% confidence interval (95% CI) 1.09 to 2.87] with respect to controls. Women employed in domestic service sector for a long time had an OR of 2.06 (95% CI 1.15 to 3.66). Conclusion: We confirmed and redefined the association of lung cancer with occupational cleaning, which concerns a considerable proportion of women workers.

Night work and prostate cancer risk: results from the EPICAP Study

Objective To investigate the role of night work in prostate cancer based on data from the EPICAP Study. Methods EPICAP is a French population-based case-control study including 818 incident prostate cancer cases and 875 frequency-matched controls that have been interviewed face to face on several potential risk factors including lifetime occupational history. Detailed information on work schedules for each job (permanent or rotating night work, duration, total number of nights, length of the shift, number of consecutive nights) as well as sleep duration and chronotype, was gathered. Prostate cancer aggressiveness was assessed by Gleason Score. Results Night work was not associated with prostate cancer, whatever the aggressiveness of prostate cancer, while we observed an overall increased risk among men with an evening chronotype (OR=1.83, 95%u2009CI 1.05 to 3.19). A long duration of at least 20 years of permanent night work was associated with aggressive prostate cancer (OR=1.76, 95%u2009CI 1.13 to 2.75), even more pronounced in combination with a shift length >10u2009hours or ≥ 6u2009consecutive nights (OR=4.64, 95%u2009CI 1.78 to 12.13; OR=2.43, 95%u2009CI 1.32 to 4.47, respectively). Conclusion Overall, ever night work, either permanent or rotating, was not associated to prostate cancer. Nevertheless, our results suggest that a long duration of permanent night work in combination with a long shift length or at least six consecutive nights may be associated with prostate cancer, particularly with aggressive prostate cancer. Further studies are needed to confirm those findings.

Prostatitis, other genitourinary infections and prostate cancer risk: Influence of non-steroidal anti-inflammatory drugs? Results from the EPICAP study: Prostatitis, nsaids and prostate cancer

Epidemiological studies have suggested that prostatitis may increase the risk of prostate cancer due to chronic inflammation. We studied the association between several genitourinary infections and the risk of prostate cancer based on data from the EPICAP study. EPICAP is a population‐based case‐control study conducted in the département of Hérault, France, between 2012 and 2014. A total of 819 incident cases and 879 controls have been face to face interviewed using a standardized questionnaire gathering information on known or suspected risk factors of prostate cancer, and personal history of genitourinary infections: prostatitis, urethritis, orchi‐epididymitis, and acute pyelonephritis. Odds Ratios (OR) and their 95% confidence interval were estimated using multivariate unconditional logistic regression. Overall, 139 (18%) cases and 98 (12%) controls reported having at least one personal history of genitourinary infections (OR = 1.64 [1.23–2.20]). The risk increased with the number of infections (p‐trend < 0.05). The association was specifically observed with personal history of chronic prostatitis and acute pyelonephritis (OR = 2.95 [1.26–6.92] and OR = 2.66 [1.29–5.51], respectively) and in men who did not use any non‐steroidal anti‐inflammatory drugs (OR = 2.00 [1.37–2.91]). Our results reinforce the hypothesis that chronic inflammation, generated by a personal history of genitourinary infections, may play a role in prostate carcinogenesis.

Occupational exposure to textile dust and lung cancer risk: Results from the ICARE Study

BACKGROUNDnTo investigate the association of lung cancer with occupational exposure to textile dust and specifically to cotton dust in the population-based case-control study ICARE.nnnMETHODSnLifelong occupational history of 2926 cases and 3555 controls was collected using standardized questionnaires, with specific questions for textile dust exposure. Odds ratios (ORs) and 95% confidence intervals (CI) were estimated using unconditional logistic regression models controlling for confounding factors including smoking and asbestos exposure.nnnRESULTSnAn inverse association between textile dust exposure and lung cancer was found among workers exposed ≥5% of their work time (ORu2009=u20090.80, 95%CIu2009=u20090.58-1.09), more pronounced for distant exposures (40+ years; up to a 56% reduced risk, statistically significant). The OR of lung cancer was significantly decreased among workers exposed to cotton fibers (ORu2009=u20090.70, 95%CIu2009=u20090.48-0.97).nnnCONCLUSIONSnOur results provide some evidence of a decreased risk of lung cancer associated with exposure to textile dust, particularly cotton.

0156 Lung cancer among meat industry workers: results of the icare study

Purpose Lung cancer among butchers and others meat workers has been investigated in a French population based case-control study ICARE. Methods Detailed information was collected on occupational history and smoking habits from 2926 patients with histologically confirmed lung cancer and 3555 matched controls. Jobs were defined according to the international Standard Classification of Occupations (ISCO) codes and categorised according to the French Nomenclature of Activities (NAF). Smoking history was combined into a comprehensive smoking index (CSI) that included mean number of cigarettes/day, duration and time since cessation. Personal history of hand warts were used as a proxy for an eventual exposure to the HPV (2,7). Odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression models and controlled for well-established risk factors for lung cancer including smoking and occupational exposure to asbestos. Results We found an increased risk of lung cancer among meat workers (101 cases/85 controls; OR=1.46, 95% Cl=1.01–2.13), especially among those who started working before the age of 17 (OR=1.72, 95% Cl=1.08–2.74). The risk was concentrated in workers exposed to slaughtered meat including Slaughterers (ISCO code 77320) and Meat Cutters (ISCO code 77330). Associations were not affected by history of hand warts. However, pronounced inverse associations for lung cancer were shown with personal history of hand warts (OR=0.63, 95% CI=0.56–0.71). Conclusions Working in meat industry may increase risk of lung cancer suggesting the role of oncogenic viruses other than HPV. Associations with history of hand warts remain to be clarified by future studies.

0371 Night shift work and prostate cancer risk: results from the epicap study

Background In 2007, the International Agency for Research on Cancer classified ”shift work leading to a disruption of circadian rhythm” as probably carcinogenic to humans based on sufficient evidence from experimental animal models but limited evidence from epidemiological studies in humans. In this context, we investigated the role of night shift work in prostate cancer based on data from the EPICAP study. Methods EPICAP is a French population-based case-control study including 819 incident prostate cancer cases and 879 frequency matched controls. Cases and controls were face-to-face interviewed on their lifetime occupational history with details on work schedules for each job held for ≥6 months. Night work was defined as having performed permanent or rotating night shifts for at least 270u2009hours/year or 3 nights/month during ≥1u2009year. Results Permanent and rotating night work were not associated with prostate cancer (OR=0.99 [0.78–1.26], OR=0.89 [0.66–1.20], respectively]). However, permanent night work was associated with aggressive prostate cancer (OR=1.40 [0.97–2.03]), especially for a duration greater than 25 years (1.89 [1.15–3.11]). Interestingly, an association between night work and prostate cancer risk was observed for men with an evening chronotype (OR=1.82 [1.01–3.28]), especially for rotating night work (OR=2.34 [1.02–5.35]). Conclusion Our results suggest that night work may be associated with prostate cancer, particularly in men with aggressive prostate cancer or with an evening chronotype. Further investigations are needed to confirm our findings and to take into account a potential influence of an individual susceptibility to circadian genes in this association.