Structure and polymorphisms of human aryl hydrocarbon receptor repressor (AhRR) gene in a French population: relationship with CYP1A1 inducibility and lung cancer.

International audienceOBJECTIVE: The aryl hydrocarbon receptor repressor (AhRR) protein may dimerize with the AhR nuclear translocator (ARNT) and may compete with the aryl hydrocarbon receptor (AhR) to bind the xenobiotic responsive elements. The result is a negative feedback mechanism that involves a down regulation of all genes regulated by the AhR transcription factor which positively regulates the expression of the Cytochrome P-4501A1 gene (CYP1A1). METHODS: The structure of the AhRR gene was reconstituted, then the genetic polymorphisms of this gene including the promoter were investigated and the link between these polymorphisms, CYP1A1 inducibility and lung cancer incidence in a French population was examined. Four polymorphisms were found, two in the coding region (609G>C and 1977G>C) and two in the 5'-untranslated region (-96G>A and -869A>T). Among the four polymorphisms, only one, the 609G>C has been previously described. The 609G>C and 1977G>C are localized respectively in exon 6 and 12 and lead to Pro554Ala and Asp641His substitutions, respectively. To evaluate the frequency of these allelic variants, a DNA library of a case-control study of lung cancer (164 controls and 171 patients) was screened. These polymorphisms were detected at the same allele frequency (0.40 for 609C, 0.05 for 1977C, 0.24 for -96A and 0.17 for -869T) in both controls and patients. Statistical analysis did not show any relationship between all the mutations found and CYP1A1 inducibility and lung cancer incidence. CONCLUSION: None of the polymorphisms were found to play a key role in CYP1A1 inducibility or in the susceptibility to develop lung cancer

Cohort mortality study among French asphalt workers.

BACKGROUND: In conjunction with the European cohort study among asphalt workers coordinated by the International Agency for Research on Cancer (IARC), we studied the mortality of 15,011 French men who were followed for 17 years for a total of 175,062 persons-years. This group contained 2,506 subjects who had ever been employed as asphalt workers: they contributed 30,692 person-years of risk. A reference group was composed of 6,675 subjects (i.e., 61,856 persons-years) who had been employed only in building or ground construction. METHODS: Mortality ratios standardized for age and period were computed with their 95% confidence intervals (CI) from the age and period mortality rates of all French men for the years covered by the study (1979-1996). We also compared the mortality of exposed workers and the reference group with Poisson regression models after adjustment for age, calendar period, and either duration of employment or length of follow-up. RESULTS: Mortality from lung cancer was equivalent to the expected rate [SMR = 1.01 95% CI (0.6-1.6)], but was 40% greater than among the non-exposed reference group [RR = 1.4 95% CI (0.7-2.8)]. We also found an excess of gastrointestinal cancers, especially of the esophagus [SMR = 1.94, 95% CI (0.9-3.6)] and stomach [SMR = 2.2, 95% CI (0.8-4.7)]. Comparison with the internal reference group confirmed these findings, especially for stomach cancer [RR = 2.8, 95% CI (0.7-11.4)]. CONCLUSIONS: Although our results are not statistically significant, they suggest that road-paving workers may have a slightly higher rate of lung cancer and a moderately higher rate of stomach cancer than their non-exposed counterparts. The excess of lung cancer may be due to potential confounding factors, including the occupational risk factor of coal tar exposure and the lifestyle risk factor of smoking. A nested case-control study is under way that will make it possible to control for smoking and other potential carcinogenic exposures; this is necessary before any definitive conclusions can be drawn

Breast cancer risk in relation to ambient concentrations of nitrogen dioxide and particulate matter: results of a population-based case-control study corrected for potential selection bias (the CECILE study)

Background: There is only scant evidence that air pollution increases the risk of breast cancer. Objectives: We investigated this relationship for three air pollutants: nitrogen dioxide (NO2) and particulate matter with an aerodynamical diameter below 10 µm (PM10) and 2.5 µm (PM2.5). Methods: We conducted a population-based case-control study on breast cancer in two French départements, including 1,229 women diagnosed with breast cancer in 2005–2007 and 1,316 control women frequency-matched on age. Concentrations of NO2, PM10 and PM2.5 at participants’ addresses occupied during the last 10 years were assessed using a chemistry transport model. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using multivariable logistic regression models where each woman was assigned a weight depending on her probability of selection into the study. Results: The OR for breast cancer per 10-µg/m3 increase in NO2 was 1.11 (95% CI, 0.98, 1.26), and 1.41 (95% CI 1.07, 1.86) in the highest exposure quintile (Q5), compared to the first. The ORs per 10-µg/m3 NO2 did not markedly differ between pre- (OR 1.09, 95% CI 0.89, 1.35)) and post-menopausal women (OR 1.14, 95% CI 0.97, 1.33)), but the OR was substantially higher for hormone-receptor positive (ER+/PR+) breast tumor subtypes (OR 1.15, 95% CI 1.00, 1.31) than for ER–/PR– tumors (OR 0.95, 95% CI 0.72, 1.26). Breast cancer risk was not associated with either PM10 (OR per 1 µg/m3 1.01, 95% CI, 0.96, 1.06) or PM2.5 (OR per 1 µg/m3 1.02, 95% CI 0.95, 1.08), regardless of the menopausal status or of the breast tumor subtype. Discussion: Our study provides evidence that NO2 exposure, a marker of traffic-related air pollutants, may be associated with an increased risk of breast cancer, particularly ER+/PR+ tumors

Abdominal obesity and prostate cancer risk: epidemiological evidence from the EPICAP study

International audienceObesity is associated with an increased risk of several cancers, but inconsistent results have been observed between body mass index (BMI) and prostate cancer (PCa) risk. However, some associations have been reported with other indicators such as waist circumference (WC) and waist-hip ratio (WHR). We investigated the role of anthropometric indicators in PCa risk based on data from the Epidemiological study of Prostate Cancer (EPICAP). EPICAP is a population-based case-control study that included 819 incident PCa in 2012-2013 and 879 controls frequency matched by age. Anthropometric indicators (weight, height, WC, and hip circumference) have been measured at interview. Logistic regression models were used to assess odds ratios (ORs) for the associations between anthropometric indicators (BMI, WC and WHR) and PCa risk. We observed a slight, but not significant increased risk of PCa for men with a WC > 94 cm (OR 1.20, 95% CI 0.92-1.56) and for men with a WHR ≥ 0.95 (OR 1.30, 95% CI 1.00-1.70 between 0.95 and 1.00, OR 1.25, 95% CI 0.96-1.61 above 1.00). Associations were more pronounced after adjustment and stratification for BMI and in men with aggressive PCa. Our results suggest that abdominal obesity may be associated with an increased risk of PCa, especially aggressive PCa

Sleep Patterns and Risk of Prostate Cancer: A Population-Based Case Control Study in France (EPICAP)

International audienceAbstract Background: Sleep disturbances have been singled out for their implication in the risk of several cancer sites. However, results for prostate cancer are still inconsistent. Methods: We used data from the EPICAP study, a French population-based case–control study including 819 incident prostate cancer cases and 879 controls frequency matched by age. Detailed information on sleep duration on work/free days, and sleep medication over lifetime was collected. Results: Sleep duration and sleep deprivation were not associated with prostate cancer, whatever the aggressiveness of prostate cancer. However, sleep deprivation was associated with an increased prostate cancer risk among men with an evening chronotype [OR, 1.96; 95% confidence interval (CI), 1.04–3.70]. We also observed an increased risk of prostate cancer with higher duration of sleep medication use (Ptrend = 0.008). This association with long duration of sleep medication use (≥10 years) was more pronounced among men who worked at night 15 years or more (OR, 3.84; 95% CI, 1.30–11.4) and among nonusers of NSAID (OR, 2.08; 95% CI, 1.15–3.75). Conclusions: Our results suggested that chronotype, night work, or NSAID use could modify the association between sleep disorders and prostate cancer occurrence needing further investigations to go further. Impact: EPICAP is the first study, which investigates several sleep indicators taking into account potential effect modifiers. If our findings were confirmed, we could identify subgroups of men at higher risk of prostate cancer that may be accessible to preventive measures

Diabetes, metabolic syndrome and prostate cancer risk: Results from the EPICAP case-control study

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Body mass index trajectories and prostate cancer risk: Results from the EPICAP study

International audienceElevated body mass index (BMI) has been inconsistently associated with prostate cancer occurrence but it has been suggested that life course adulthood obesity may be associated with an increased risk of prostate cancer. However, few studies have investigated lifetime BMI and prostate cancer risk. We analyzed life course BMI trajectories on prostate cancer risk based on data from the Epidemiological study of Prostate Cancer (EPICAP). We included in our analyses 781 incident prostate cancer cases and 829 controls frequency matched by age. Participants were asked about their weight every decade from age 20 to two years before reference date. BMI trajectories were determined using group-based trajectory modeling to identify groups of men with similar patterns of BMI changes. We identified five BMI trajectories groups. Men with a normal BMI at age 20 developing overweight or obesity during adulthood were at increased risk of aggressive prostate cancer compared to men who maintained a normal BMI. Our results suggest that BMI trajectories resulting in overweight or obesity during adulthood are associated with an increased risk of aggressive prostate cancer, particularly in never smokers, emphasizing the importance of maintaining a healthy BMI throughout adulthood

Hepatocellular Carcinoma and Occupation in Men: A Case-Control Study.

International audienceOBJECTIVE:: The principal objective of this work was to evaluate the association between the risk of hepatocellular carcinoma (HCC) and various occupations. METHODS:: This case-control study, conducted during 2000 to 2003 in four French hospitals, included 125 men younger than 75 years with incident HCC and 142 men as control subjects. RESULTS:: An association with HCC was observed for machinery fitters and machine assemblers (odds ratio [OR] = 4.4 [1.0-19.0], eight exposed cases and three exposed controls). A higher percentage of cases than controls were metal machinists (OR = 2.2 [0.8-5.8], 14 exposed cases and 10 exposed controls), although the difference was not statistically significant. These associations were strongest for subjects with duration of employment greater than 20 years. CONCLUSIONS:: Our findings suggest an association between metal machining jobs and hepatocellular carcinoma, although we cannot rule out the possibility that it was observed by chance

P rostatitis, other genitourinary infections and prostate cancer risk: I nfluence of non‐steroidal anti‐inflammatory drugs? R esults from the EPICAP study

International audienceEpidemiological 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