Relationship between night work and health-related quality of life: an analysis based on profiles and cumulative duration of exposure to night work among French workers in the CONSTANCES cohort.

OBJECTIVE: The aim of this study is to estimate the association between night work and health-related quality of life (HRQoL) among French workers. The association between cumulative duration of night work and HRQoL was also investigated. METHODS: Three career-long night work exposure groups were defined at inclusion in the CONSTANCES cohort: permanent night workers, rotating night workers and former night workers. Day workers with no experience of night work were the reference group. HRQoL was assessed using the Short Form Health Survey (SF-12), in particular the physical component summary (PCS) and mental component summary (MCS) scores, with a higher score indicating better HRQoL. Several linear regression models were built to test the association between night work exposure and HRQoL. The relationship between cumulative duration of night work and HRQoL scores was analyzed using generalised additive models. RESULTS: The sample consisted of 10,372 participants. Former night workers had a significantly lower PCS score than day workers (ß [95% CI]: - 1.09 [- 1.73; - 0.45], p = 0.001), whereas permanent night workers had a significantly higher MCS score (ß [95% CI]: 1.19 [0.009; 2.36], p = 0.048). A significant decrease in PCS score from 5 to 20 years of cumulative night work was observed among former night workers. CONCLUSIONS: Former night workers had poorer physical HRQoL in contrast to permanent and rotating night workers who had similar or even better HRQoL than day workers, suggesting the well-known healthy worker survivor effect. Consequently, both current and former night workers require regular and specific follow-up focused on the physical components of their health.

Is the effect of work-related psychosocial exposure on depressive and anxiety disorders short-term, lagged or cumulative?

PURPOSE: To determine the short-term, lagged, and cumulative effects of psychosocial factors (PSF) on the incidence of depression and anxiety. METHOD: Major depressive disorders (MDD) and generalized anxiety disorders (GAD) were diagnosed in 2006 and 2010 using the Mini International Neuropsychiatric Interview among 5684 workers from the French SIP cohort. The outcome considered here was diagnosis of MDD and/or GAD (MDD/GAD) in 2010. The frequency of 17 PSF, covering labour intensity and working time, emotional demand, autonomy, social relationships, conflict of values, and job insecurity, was self-reported in 2006 and 2010. For each PSF, four groups (A-D) were considered: exposed neither in 2006 nor in 2010 (A as the reference), exposed in 2010 but not in 2006 (B as a short-term association), exposed in 2006 but not in 2010 (C as a lagged association), exposed in both 2006 and 2010 (D as a cumulative association). RESULTS: In men, short-term and cumulative-and to a lesser extent lagged-associations of four labour-intensity factors with MDD/GAD occurrence were observed (high volume of work, pressure at work, high complexity, and long working hours). In women, the short-term and cumulative associations of five PSF were observed, mostly emotional demand factors, lack of reward and work-family imbalance. Job insecurity had strong, short-term, cumulative and lagged associations in both men and women. CONCLUSION: According to PSF and gender, the results suggest that the relationships between PSF exposure and MDD/GAD were mostly short-term and cumulative rather than lagged.

Bladder cancer and occupational exposure to metalworking fluid mist: a counter-matched case-control study in French steel-producing factories.

OBJECTIVES: To assess the relationship between occupational exposure to metalworking fluids (MWFs) in the steel-producing industry and bladder cancer incidence. METHODS: A nested case-control study on bladder cancer was set up in a cohort of workers from six French steel-producing factories. Three controls were randomly selected for each incident bladder cancer case diagnosed from 2006 to 2012. Controls were matched to cases on age at diagnosis and counter-matched on a surrogate measure of exposure to MWFs derived from a job-exposure matrix. Cases (n=84) and controls (n=251) were face-to-face interviewed. Experts assessed occupational exposure to MWFs (straight, soluble and synthetic) using questionnaires and reports from factory visits. Occupational exposures were based on three metrics: duration, frequency-weighted duration and cumulative exposure index. Conditional multiple logistic regressions were used to determine ORs and 95% CIs, taking non-occupational and occupational exposure into account. RESULTS: In the 25 years before diagnosis, ORs increased significantly with duration of exposure to straight MWFs (OR=1.13 (1.02-1.25)) and increased with frequency-weighted duration of exposure to straight MWFs (OR=1.44 (0.97-2.14)). These results remained valid after adjusting for duration of smoking, average number of cigarettes smoked per day, time since smoking cessation and exposure to polycyclic aromatic hydrocarbons (PAHs). ORs also increased with soluble MWFs but not significantly. No significant association was found with older exposures to MWFs or with exposure to synthetic MWFs. CONCLUSION: The increased risk of bladder cancer observed among workers exposed to straight MWFs and to a lesser extent to soluble MWFs may be explained by the presence of carcinogens (such as PAH) in mineral oils component of straight and soluble oils. Prevention therefore remains necessary in sectors using MWFs.

Predictions of survival up to 10 years after diagnosis for European women with breast cancer in 2000-2002.

Few studies have addressed longer-term survival for breast cancer in European women. We have made predictions of 10-year survival for European women diagnosed with breast cancer in 2000-2002. Data for 114,312 adult women (15-99 years) diagnosed with a first primary malignant cancer of the breast during 2000-2002 were collected in the EUROCARE-4 study from 24 population-based cancer registries in 14 European countries. We estimated relative survival at 1, 5, and 10 years after diagnosis for women who were alive at some point during 2000-2002, using the period approach. We also estimated 10-year survival conditional on survival to 1 and 5 years after diagnosis. Ten-year survival exceeded 70% in most regions, but was only 54% in Eastern Europe, with the highest value in Northern Europe (about 75%). Ten-year survival conditional on survival for 1 year was 2-6% higher than 10-year survival in all European regions, and geographic differences were smaller. Ten-year survival for women who survived at least 5 years was 88% overall, with the lowest figure in Eastern Europe (79%) and the highest in the UK (91%). Women aged 50-69 years had higher overall survival than older and younger women (79%). Six cancer registries had adequate information on stage at diagnosis; in these jurisdictions, 10-year survival was 89% for local, 62% for regional and 10% for metastatic disease. Data on stage are not collected routinely or consistently, yet these data are essential for meaningful comparison of population-based survival, which provides vital information for improving breast cancer control.

True and false autobiographical memories in schizophrenia: preliminary results of a diary study.

The frequency of true and false autobiographical memories and associated states of conscious awareness, i.e., conscious recollection and simply knowing, as well as the respective roles of affective and cognitive processes in autobiographical memory construction, were assessed in eight patients with schizophrenia and eight control participants. A diary study methodology was used in combination with the Remember/Know procedure. The results showed a higher frequency of Know responses associated with the retrieval of both true and false memories in patients than in control participants. Whereas control participants rated higher at retrieval than at encoding the distinctiveness and personal importance of events, as well as the extent to which events furthered current personal plans, patients exhibited an opposite pattern of ratings, with ratings being lower at retrieval than at encoding. These preliminary results show a high frequency of simply knowing associated with the retrieval of true and false autobiographical memories in patients with schizophrenia and provide evidence for the interest of the diary study methodology for studying autobiographical memory in schizophrenia.

HIV-related excess mortality and age-related comorbidities in patients with HIV aged ≥60: a relative survival analysis in the French Dat'AIDS cohort.

OBJECTIVE: The objective was to evaluate the association between age-related comorbidities (ARCs) and 5-year HIV-related excess mortality in people living with HIV aged ≥60 years. DESIGN: Cohort study using relative survival analysis (Estève's model). SETTING: The French multicentre prospective Dat'AIDS cohort that involves 12 French hospitals. PARTICIPANTS: Inclusion of 1415 HIV-1 infected patients actively followed aged ≥60 years on January 2008, with a 5-year follow-up period in the late combination antiretroviral therapy era. RESULTS: Among 1415 patients included, 154 died. By multivariable analysis, factors predictive of 5-year HIV-related excess mortality were non-AIDS-related cancer (adjusted excess HR (aEHR)=2.94; 95% CI 1.32 to 6.57), cardiovascular disease (aEHR=6.00; 95% CI 2.45 to 14.65), chronic renal disease (aEHR=4.86; 95% CI 2.24 to 10.53), cirrhosis (aEHR=3.58; 95% CI 1.25 to 10.28), hepatitis C co-infection (aEHR=3.63; 95% CI 1.44 to 9.12), body mass index<18.5 kg/m² (aEHR=4.10; 95% CI 1.61 to 10.48) and having a CD4 cell count ≤200/mm3 (aEHR=5.79; 95% CI 2.28 to 14.69). CONCLUSIONS: ARCs, particularly cardiovascular disease and chronic renal disease, are predictive of HIV-related excess mortality, with an increase in hazard similar to that of CD4 cell count. TRIAL REGISTRATION NUMBER: NCT02898987.

Ten-year survival and risk of relapse for testicular cancer: a EUROCARE high resolution study.

Effective treatments for testicular cancer have been available since the 1970s, yet EUROCARE uncovered marked inter-country survival differences for this disease. To investigate these differences, we reviewed clinical records of 1350 testicular cancer cases diagnosed during 1987-1992 from 13 population-based cancer registries in nine European countries. Patients were followed up for life status and relapse. Ten-year observed survival was estimated by the Kaplan-Meier method. Cox multivariable analyses were performed separately for seminomas and non-seminomas. Overall, 66% of seminomas and 36% of non-seminomas were limited to the testis. Ten-year survival was 63% (Estonia) to 94% (Switzerland, Slovenia) for seminoma; 47% (Estonia) to 90% (Yorkshire, UK, The Netherlands) for non-seminoma. Multivariable analysis adjusted for country, age and stage showed that hazard ratios (HRs) of death differed little between western European registries, and were mainly attributable to differing stage at diagnosis. Significantly higher than reference HRs in Estonia and Poland suggest inadequacy or unavailability of treatments.

Early markers of prolonged hospital stays in older people: a prospective, multicenter study of 908 inpatients in French acute hospitals.

OBJECTIVES: To identify early markers of prolonged hospital stays in older people in acute hospitals. DESIGN: A prospective, multicenter study. SETTING: Nine hospitals in France. PARTICIPANTS: One thousand three hundred six patients aged 75 and older were hospitalized through an emergency department (Sujet Agé Fragile: Evaluation et suivi (SAFEs)--Frail Elderly Subjects: Evaluation and follow-up). MEASUREMENTS: Data used in a logistic regression were obtained through a gerontological evaluation of inpatients, conducted in the first week of hospitalization. The center effect was considered in two models as a random and fixed effect. Two limits were used to define a prolonged hospital stay. The first was fixed at 30 days. The second was adjusted for Diagnosis Related Groups according to the French classification (f-DRG). RESULTS: Nine hundred eight of the 1,306 hospital stays that made up the cohort were analyzed. Two centers (n=298) were excluded because of a large volume of missing f-DRGs. Two-thirds of subjects in the cohort analyzed were women (64%), with a mean age of 84. One hundred thirty-eight stays (15%) lasted more than 30 days; 46 (5%) were prolonged beyond the f-DRG-adjusted limit. No sociodemographic variables seemed to influence the length of stay, regardless of the limit used. For the 30-day limit, only cognitive impairment (odds ratio (OR)=2.2, 95% confidence interval (CI)=1.2-4.0) was identified as a marker for prolongation. f-DRG adjustment revealed other clinical markers. Walking difficulties (OR=2.6, 95% CI=1.2-16.7), fall risk (OR=2.5, 95% CI=1.7-5.3), cognitive impairment (OR=7.1, 95% CI=2.3-49.9), and malnutrition risk (OR=2.5, 95% CI=1.7-19.6) were found to be early markers for prolonged stays, although dependence level and its evolution, estimated using the Katz activity of daily living (ADL) index, were not identified as risk factors. CONCLUSION: When the generally recognized parameters of frailty are taken into account, a set of simple items (walking difficulties, risk of fall, risk of malnutrition, and cognitive impairment) enables a predictive approach to the length of stay of elderly patients hospitalized under emergency circumstances. Katz ADLs were not among the early markers identified.

Effects of occupational exposure to poorly soluble forms of beryllium on biomarkers of pulmonary response in exhaled breath of workers in machining industries.

OBJECTIVE: To analyze the effects of occupational exposure to poorly soluble forms of beryllium (Be) on biomarkers of pulmonary inflammation using exhaled breath condensate (EBC) in workers employed in machining industries. METHODS: Twenty machining operators were compared to 16 controls. The individual exposure to Be was assessed from the work history with several indices of exposure calculated on the basis of task-exposures matrices developed for each plant using historical air measurements. Clinical evaluation consisted in a medical questionnaire, measurements of biomarkers in EBC (tumor necrosis factor alpha (TNF-α), total nitrogen oxides (NOx)), measurement of the fraction of exhaled nitric oxide (FeNO) and resting spirometry. Adjusted multiple linear regressions were used to study the effect of the exposure to Be on inflammatory biomarkers. RESULTS: Levels of TNF-α and NOx in EBC were not statistically different between exposed and controls. We found a statistically significant relationship between levels of TNF-α in EBC and both index of cumulative exposure and duration of exposure to Be. No other statistically significant relationships were found between exposure to Be and pulmonary response. CONCLUSION: Our results suggest that machining-related exposure to Be is related to pulmonary inflammation involving TNF-α. These findings must be confirmed by larger studies.

Geographical Heterogeneity of Multiple Sclerosis Prevalence in France.

INTRODUCTION: Geographical variation in the prevalence of multiple sclerosis (MS) is controversial. Heterogeneity is important to acknowledge to adapt the provision of care within the healthcare system. We aimed to investigate differences in prevalence of MS in departments in the French territory. METHODS: We estimated MS prevalence on October 31, 2004 in 21 administrative departments in France (22% of the metropolitan departments) by using multiple data sources: the main French health insurance systems, neurologist networks devoted to MS and the Technical Information Agency of Hospitalization. We used a spatial Bayesian approach based on estimating the number of MS cases from 2005 and 2008 capture-recapture studies to analyze differences in prevalence. RESULTS: The age- and sex-standardized prevalence of MS per 100,000 inhabitants ranged from 68.1 (95% credible interval 54.6, 84.4) in Hautes-Pyrénées (southwest France) to 296.5 (258.8, 338.9) in Moselle (northeast France). The greatest prevalence was in the northeast departments, and the other departments showed great variability. DISCUSSION: By combining multiple data sources into a spatial Bayesian model, we found heterogeneity in MS prevalence among the 21 departments of France, some with higher prevalence than anticipated from previous publications. No clear explanation related to health insurance coverage and hospital facilities can be advanced. Population migration, socioeconomic status of the population studied and environmental effects are suspected.

Women and small cell lung cancer: social characteristics, medical history, management and survival: a retrospective study of all the male and female cases diagnosed in Bas-Rhin (Eastern France) between 1981 and 1994.

The literature make it clear that lung cancer in women differs from that in men in several specific aspects. We conducted a retrospective study of the 967 consecutive recorded patients (696 men and 91 women after exclusions) diagnosed with small cell lung cancers (SCLC) between 1981 and 1994 in the Bas-Rhin population-based cancer registry to determine if such particularities could be observed in SCLC. Data included demographic and social characteristics, medical and smoking history, management (diagnosis and treatment), hospitalisation and survival. The end point for survival was 31 December 1998. Women were more frequently single, divorced, or widowed (P=0.007) and lived more often in urban areas (places with more than 10,000 inhabitants) (P=0.017). They differed significantly from men in their tobacco exposure (P=0.0001) and non-smoking rates (P=0.0003) but not in clinical presentation, except for more frequently elevated LDH levels (P=0.02). Bone marrow biopsies were more often performed in men (P=0.004), but management was otherwise comparable. The mean number of hospitalisations (for any reason) was comparable in both sexes but women tended to remain hospitalised longer (P=0.057). Overall survival did not differ, but women older than 70 years died sooner than their male counterparts (P=0.026). Our study confirms that some of gender differences reported in the lung cancer literature exist in SCLC. Sex-related differences in LDH levels have not previously been reported, to our knowledge. North American and European data concerning survival among women and men are discordant. Whether these gender differences are related to a real difference between the sexes or simply to differential exposure to carcinogens remains to be determined.

Relations between emotion and conscious recollection of true and false autobiographical memories: an investigation using lorazepam as a pharmacological tool.

RATIONALE: Conscious recollection for autobiographical memory is the subjective experience of reliving a personal event mentally. Its frequency is strongly influenced by the emotion experienced at the time of the event. OBJECTIVE: We addressed the issue of whether conscious recollection for autobiographical memories is also influenced by the emotion experienced at the time of retrieval. We used lorazepam, a benzodiazepine, as a pharmacological tool to modulate this emotional experience. METHODS: Autobiographical memories were recorded in eight healthy volunteers using a diary study methodology. Each day, four entries were made by each subject: two true events, one altered event and one false event. For each event, the subjects were asked to rate emotional variables at encoding and at retrieval. Two months later, there were two sessions of recognition tests during which the subjects received orally an acute administration of either lorazepam (0.038 mg/kg) or placebo using a cross-over design. Subjective states of awareness were assessed using the Remember/Know/Guess procedure. RESULTS: Compared to placebo, lorazepam increased levels of conscious recollection, as assessed by Remember responses, for both true and false memories and induced an overestimation of the personal significance and emotional intensity of past events. Structural equation modelling showed that this overestimation was causal in the increased frequency of conscious recollection. CONCLUSIONS: Our results provide experimental evidence that the frequency of conscious recollection for both true and false autobiographical memories is influenced by the emotion experienced at the time of retrieval.

Chronic persecutory delusion and autobiographical memories in patients with schizophrenia: a diary study.

BACKGROUND: While chronic persecutory delusions are typically anchored into patients' everyday life situations, no investigation has ever looked at how situations associated with a feeling of persecution are recorded and later retrieved. METHOD: a diary methodology combined with a recognition task involving ten patients with schizophrenia who presented chronic persecutory delusions and ten control participants. Diaries of everyday persecutory events (Pe) and non-persecutory events (nPe) were kept. RESULTS: in both groups, 1) Pe were associated with higher anxiety scores than nPe, 2) Pe were experienced as less distinctive and more stereotyped than nPe, 3) the frequency of incorrect recognition of altered descriptions of Pe was higher than that of nPe. LIMITATIONS: because high levels of motivation are required of the diarists, our sample size was small. CONCLUSION: Memories of persecutory events were highly emotional and semanticized. they were frequently incorrectly recognized, suggesting the existence of bias resulting from interactions between their processing and persecutory delusions.

The role of circumstances of diagnosis and access to dermatological care in early diagnosis of cutaneous melanoma: a population-based study in France.

OBJECTIVES: To describe circumstances of the diagnosis and access to dermatological care for patients with cutaneous melanoma (CM) and to investigate factors associated with early detection. DESIGN: Retrospective population-based study of incident cases of invasive CM in 2004, using questionnaires to physicians and a survey of cancer registries and pathology laboratories. SETTING: Five regions in northeastern France. PATIENTS: Six hundred fifty-two patients who were referred to dermatologists by general practitioners (group 1) or by other specialists (group 2), who directly consulted a dermatologist for CM (group 3), or who were diagnosed as having CM during a prospective follow-up of nevi (group 4) or when consulting a dermatologist for other diseases (group 5). MAIN OUTCOME MEASURES: Characteristics of patients, tumors, and patients' residence in each group, including the geographical concentration of dermatologists. We performed multivariate analysis of these factors to determine association with Breslow thickness. RESULTS: Age, tumor location, Breslow thickness, ulceration, histological type, and geographical concentration of dermatologists significantly differed among groups. Patients consulting dermatologists directly formed the largest group (45.1%). Those referred by general practitioners (26.1%) were the oldest and had the highest frequency of thick (>3 mm), nodular, and/or ulcerated CM. Patients from groups 4 (8.4%) and 5 (14.1%) had the thinnest CMs. Ulcerated and/or thick tumors were absent in group 4. In multivariate analysis, histological types superficial spreading melanoma and lentigo maligna melanoma, younger age, high concentration of dermatologists, and detection by dermatologists were significantly associated with thinner CMs. CONCLUSION: Easy access of patients to dermatologists, information campaigns targeting elderly people, and education of general practitioners are complementary approaches to improving early detection.

Variation in 'standard care' for breast cancer across Europe: a EUROCARE-3 high resolution study.

On a population-based sample of 13,500 European breast cancer patients mostly diagnosed in 1996-1998 and archived by 26 cancer registries, we used logistic regression to estimate odds of conservative surgery plus radiotherapy (BCS+RT) versus other surgery, in T1N0M0 cases by country, adjusted for age and tumour size. We also examined: BCS+RT in relation to total national expenditure on health (TNEH); chemotherapy use in N+ patients; tamoxifen use in oestrogen-positive patients; and whether 10 nodes were examined in lymphadenectomies. Stage, diagnostic examinations and treatments were obtained from clinical records. T1N0M0 cases were 33.0% of the total. 55.0% of T1N0M0 received BCS+RT, range 9.0% (Estonia) to 78.0% (France). Compared to France, odds of BCS+RT were lower in all other countries, even after adjusting for covariates. Women of 70-99 years had 67% lower odds of BCS+RT than women of 15-39 years. BCS+RT was 20% in low TNEH, 58% in medium TNEH, and 64% in high TNEH countries. Chemotherapy was given to 63.0% of N+ and 90.7% of premenopausal N+ (15-49 years), with marked variation by country, mainly in post-menopause (50-99 years). Hormonal therapy was given to 55.5% of oestrogen-positive cases, 44.6% at 15-49 years and 58.8% at 50-99 years; with marked variation across countries especially in premenopause. The variation in breast cancer care across Europe prior to the development of European guidelines was striking; older women received BCS+RT much less than younger women; and adherence to 'standard care' varied even among countries with medium/high TNEH, suggesting sub-optimal resource allocation.

Association of cigarette smoking but not alcohol consumption with cutaneous lupus erythematosus.

OBJECTIVE: To ascertain whether smoking or alcohol consumption is associated with lupus erythematosus (LE), because this topic is still subject to debate and part of the debate could be related to the fact that smoking and alcohol consumption are specific risk factors for cutaneous LE. DESIGN: Prospective multicenter case-control study. SETTING: Three French university hospitals. Patients One hundred eight patients with LE and 216 control subjects. Intervention Standardized questionnaire evaluating cigarette smoking and alcohol consumption. MAIN OUTCOME MEASURES: The statistical significance of smoking history and alcohol consumption as associated risk factors for LE by estimating matched case-control odds ratios and their 95% confidence intervals, using multiple conditional logistic regression and the Breslow-Day test to investigate differences in quantities of cigarette and alcohol consumption. RESULTS: Of the LE patients, 73.1% smoked compared with 49.5% of controls, (odds ratio, 2.77; 95% confidence interval, 1.63-4.76). There was no significant difference in alcohol consumption between LE patients and controls. Among the 79 LE patients who smoked, 72 (91.1%) had started smoking before the first manifestation of LE (mean delay between initiation of smoking and first signs of LE, 14.1 years). The LE patients smoked significantly more than controls did (11.7 vs 7.0 pack-years; P = .002). The prevalence of smoking among patients who met more than 4 American College of Rheumatology (ACR) criteria and/or with antinuclear DNA antibodies was lower than the prevalence in patients who met fewer than 4 ACR criteria or than the prevalence in controls (P < .001). CONCLUSIONS: Cigarette smoking is associated with LE, but alcohol consumption is not. The risk conferred by cigarette smoking seems highest in patients who meet fewer than 4 ACR criteria and/or who do not have antinuclear DNA antibodies.

Conditional relative survival of cancer patients and conditional probability of death: a French National Database analysis.

BACKGROUND: Little information is available on the conditional probabilities of death among patients who survive for >5 years after a diagnosis with cancer. The objective of this study was to estimate the conditional probabilities of death for breast cancer, prostate cancer, colorectal cancer, and lung cancer in France. METHODS: The study included data from the French Network of Cancer Registries from 205,562 patients aged <75 years who were diagnosed with cancer between 1989 and 1997. The conditional probabilities of death were calculated by using a relative survival regression model in which age was included as a covariate. RESULTS: After the first year and until 10 years after diagnosis, the annual probability of death decreased dramatically for colorectal cancer: It was the same in all age groups after 3 years, and it was approximately 1% at 10 years. For prostate cancer, the decrease was not as great, and the conditional probability of death remained higher among younger patients at >4% at 10 years. During the 3 years after diagnosis, the probability of death was greater for older patients with breast cancer; then, it decreased less for younger patients compared with older patients, leading to a greater conditional probability of death among younger patients at 4 years and up to 10 years. The annual probability of death in patients with lung cancer decreased for both sexes but remained substantially higher for men than for women, reaching approximately 8% and 5%, respectively, at 10 years. CONCLUSIONS: Further studies would facilitate a better understanding of the observed differences in relative survival within European countries.

Oral contraceptive use and BRCA penetrance: a case-only study.

BACKGROUND: Women with deleterious mutations in BRCA genes are at increased risk of breast cancer. However, the penetrance of the genetic trait may be regulated through environmental factors. This multinational case-only study tested the interaction between oral contraceptive use and genetic susceptibility in the occurrence of breast cancer. METHODS: We recruited 3,123 patients diagnosed with breast cancer before the age of 45 years. Participants were classified according to their probability of carrying a BRCA mutation on the basis of their family history of breast and ovarian cancer. According to a case-only approach, the frequency of relevant exposures among breast cancer cases with high probability of BRCA mutation ("genetic cases") was compared with the frequency of the same exposures among breast cancer cases with a low probability of BRCA mutation ("sporadic cases"). The interaction odds ratios (OR) and 95% confidence intervals (CI) for oral contraceptive use were estimated by unconditional logistic regression, after controlling for potentially confounding variables. RESULTS: The analysis was carried out comparing 382 "genetic" and 1,333 "sporadic" cases. We found a borderline significant interaction between genetic breast cancer and oral contraceptive use for ever users compared with never users (OR, 1.3; 95% CI, 1.0-1.7). The greatest interaction OR was found for women who started using pill at 18 to 20 years (OR, 1.6; 95% CI, 1.1-2.3). CONCLUSION: These results suggest that BRCA mutation carriers, as well as women with a significant family history of breast and ovarian cancer are more vulnerable to exogenous hormones in oral contraceptives.

Variations in management of stage I to stage III cutaneous melanoma: a population-based study of clinical practices in France.

OBJECTIVE: To describe current management of cutaneous melanoma (CM) and identify factors accounting for disparities. DESIGN: Retrospective population-based study using survey of cancer registries and pathology laboratories, and questionnaires to physicians. SETTING: Five regions covering 19.2% of the French territory and including 8.2 million inhabitants. PATIENTS: Incident cases of patients with stage I to stage II (hereinafter, stage I-II) tumors staged according to the American Joint Committee on Cancer Staging guidelines and nodal stage III CM in 2004. MAIN OUTCOME MEASURES: Modalities of diagnosis and excision, surgical margins, sentinel lymph node biopsy, adjuvant therapies and surveillance procedures, and their variations according to age, sex, residence, location of primary CM, Breslow thickness, type of physicians, modalities of decisions, and health care patterns. RESULTS: Clinical stage I-II CMs (n = 710 cases) slightly predominated in females (53%), with a lower mean Breslow thickness (1.4 mm) than in males (1.9 mm). Initial excisions were most often performed by private dermatologists and wide excisions by surgeons. Narrow margins (8%) were associated with advanced age, higher Breslow thickness, and head location. Sentinel lymph node biopsy was performed in 34% of CMs thicker than 1.0 mm, depending on geographical regions, distance from reference centers, and health care patterns. Adjuvant therapies (mainly low-dose interferon) were proposed in 53% of thick CMs (>1.5 mm), depending on the patient's age and geographical region. In contrast with French recommendations, surveillance procedures frequently included systematic medical imaging. Stage III nodal CMs (n = 89 cases) predominated in males (62%). After lymphadenectomy, adjuvant therapies (including high-dose interferon in 32% of cases and chemotherapies in 24% of cases) were proposed in 68% of cases, depending on the patient's age and geographical region. A complete 1-year high-dose interferon regimen was administered in less than 10% of cases. CONCLUSION: Large disparities still exist in the management of CM in France, depending to a greater extent on medical and geographical environment than on the characteristics of either patients or tumors.