Validation of an algorithm for identifying incident cancer cases based on long-term illness and diagnosis related group program data from the French National Health Insurance Information System (SNDS).

PURPOSE: Three generic claims-based algorithms based on the Illness Classification of Diseases (10th revision- ICD-10) codes, French Long-Term Illness (LTI) data, and the Diagnosis Related Group program (DRG) were developed to identify retirees with cancer using data from the French national health insurance information system (Système national des données de santé or SNDS) which covers the entire French population. The present study aimed to calculate the algorithms' performances and to describe false positives and negatives in detail. METHODS: Between 2011 and 2016, data from 7544 participants of the French retired self-employed craftsperson cohort (ESPrI) were first matched to the SNDS data, and then toFrench population-based cancer registries data, used as the gold standard. Performance indicators, such as sensitivity and positive predictive values, were estimated for the three algorithms in a subcohort of ESPrI. RESULTS: The third algorithm, which combined the LTI and DRG program data, presented the best sensitivities (90.9%-100%) and positive predictive values (58.1%-95.2%) according to cancer sites. The majority of false positives were in fact nearby organ sites (e.g., stomach for esophagus) and carcinoma in situ. Most false negatives were probably due to under declaration of LTI. CONCLUSION: Validated algorithms using data from the SNDS can be used for passive epidemiological follow-up for some cancer sites in the ESPrI cohort.

Cancer Survival and Travel Time to Nearest Reference Care Center for 10 Cancer Sites: An Analysis of 21 French Cancer Registries.

BACKGROUND: The impact of several non-clinical factors on cancer survival is poorly understood. The aim of this study was to investigate the influence of travel time to the nearest referral center on survival of patients with cancer. PATIENTS AND METHODS: The study used data from the French Network of Cancer Registries that combines all the French population-based cancer registries. For this study, we included the 10 most common solid invasive cancer sites in France between 1 January 2013 and 31 December 2015, representing 160,634 cases. Net survival was measured and estimated using flexible parametric survival models. Flexible excess mortality modelling was performed to investigate the association between travel time to the nearest referral center and patient survival. To allow the most flexible effects, restricted cubic splines were used to investigate the influence of travel times to the nearest cancer center on excess hazard ratio. RESULTS: Among the 1-year and 5-year net survival results, lower survival was observed for patients residing farthest from the referral center for half of the included cancer types. The remoteness gap in survival was estimated to be up to 10% at 5 years for skin melanoma in men and 7% for lung cancer in women. The pattern of the effect of travel time was highly different according to tumor type, being either linear, reverse U-shape, non-significant, or better for more remote patients. For some sites restricted cubic splines of the effect of travel time on excess mortality were observed with a higher excess risk ratio as travel time increased. CONCLUSIONS: For numerous cancer sites, our results reveal geographical inequalities, with remote patients experiencing a worse prognosis, aside from the notable exception of prostate cancer. Future studies should evaluate the remoteness gap in more detail with more explanatory factors.

Evolution of the Incidence of Oral Cavity Cancers in the Elderly from 1990 to 2018.

OBJECTIVES: To describe the evolution of the incidence of oral cavity cancers (OCC) among elderly patients in France between 1990 and 2018 and to compare it to the incidence of other cancers sharing the same main risk factors. MATERIAL AND METHODS: The incidence of cancers in mainland France from 1990 to 2018 was estimated from incidence data observed in every cancer registry of the Francim network. Incidence was modeled by a 2-dimensional penalized spline of age and year of diagnosis, associated with a random effect corresponding to the registry. The elderly population was divided into two groups: 70-79 years old and ≥80 years old. RESULTS: There was a 72% increase in the number of OCC cases in women over 70 years of age between the periods 1990-1999 and 2010-2018. As for men, there was a stabilization in the number of cases (+2%). Over the same period, for laryngeal and hypopharyngeal cancers, there was a decrease in incidence in elderly men and an increase in elderly women, although less marked than for OCC. CONCLUSIONS: Since the 1990s, the incidence of OCC has been increasing in elderly subjects in France, particularly in women. Population aging and growth or alcohol and tobacco consumption alone do not seem to explain this increase, which is not observed in the same proportions for other upper aerodigestive tract cancer subsites sharing the same main risk factors.

Trends in incidence of invasive vaginal cancer in France from 1990 to 2018 and survival of recently diagnosed women - A population-based study.

OBJECTIVE: The aim of this study was to analyze trends in the incidence of vaginal cancer in France over a 28-year period and to present survival for recently-diagnosed women. METHODS: French cancer registries provided data on invasive vaginal cancers diagnosed from 1990 to 2015 and followed up through June 2018. Trends in incidence were analyzed using a Poisson model with a bidimensional penalized spline of age and year at diagnosis. Net survival analysis was restricted to recently-diagnosed cases (2010-2015) and used a novel approach based on a bidimensional penalized spline of age and time-since-diagnosis to model excess mortality hazard. RESULTS: With 162 new cases estimated in France in 2018, vaginal cancer represented 0.9 % of genital cancers in French women. In 2018, the world population age-standardized incidence rate was 0.2 per 100,000 person-years, median age at diagnosis was 75 years. The standardized incidence rate decreased significantly by 3 % per year (95 % CI, -3.8; -2.2) between 1990 and 2018 (0.4 cases per 100,000 person-year in 1990, vs 0.2 in 2018). Age-standardized net survival at 1 and 5 years after diagnosis was respectively 74 % and 45 %. CONCLUSIONS: This study confirms that vaginal cancer is still a rare malignancy in France with 5-year net survival that remains low. We observed a consistent decrease in the incidence rate between 1990 and 2018. It may be too early to attribute these trends to a positive impact of vaccination campaigns against hrHPV infection, since vaginal cancer mainly affects older women and HPV vaccination has only been available since the early 2000s, and only targets young girls.

To what extent do age, stage and treatment influence survival after invasive cervical cancer: a French population-based study.

PURPOSE: In an attempt to understand why cervical cancer (CC) survival is decreasing with diagnosis period among older women in France, this study aimed to estimate the effects of main prognostic factors on net survival in CC according to age. METHODS: French cancer registries databases were used to retrospectively analyze women diagnosed with CC in 2011-2012. Net survival was estimated with the Pohar-Perme method and prognostic factors (socio-demographic, clinical variables, stage at diagnosis, therapeutic management) were analyzed with Lambert and Royston's flexible parametric model. RESULTS: One thousand one hundred fifty three women with CC were identified. 30.4% were < 45, 41.4% 45-64, and 28.3% ≥ 65 years. Older women were diagnosed at a more advanced stage than younger women: 54.8% regional (FIGO IB2-IVA), 33.0% distant (IVB) in women ≥ 65 years vs 33.7% and 8.0%, respectively in women < 45 years. Half of women with regional stage of CC received recommended treatment; this rate decreased with increasing age (< 45: 66.1%, 45-64: 62.7%, ≥ 65: 29.2%). Older age was significantly associated with increased risk of death: hazard ratio 1.89 for age ≥ 65, as were regional stage (2.81), distant stage (15.99), and not receiving recommended treatment (2.26). CONCLUSION: Older women with CC diagnosed at advanced stage who do not receive standard of care are at markedly increased risk of death. Special attention to the management of older women is warranted in France, not only to diagnose cancer at an earlier stage (via gynecological follow-up in these menopaused women who remain at risk of CC), but also to ensure they receive standard of care, taking into account their overall state of health.

Adapted dietary inflammatory index and differentiated thyroid carcinoma risk in two French population-based case-control studies.

PURPOSE: Thyroid cancer is the most common endocrine cancer and its etiology is still not well understood. The aim of the present study was to assess the association between an adapted dietary inflammatory index and differentiated thyroid cancer (DTC) risk in two population-based case-control studies (CATHY and YOUNG-THYR) conducted in France. METHODS: These studies included a total of 1321 DTC cases and 1502 controls, for which an adapted dietary inflammatory index (ADII) was computed based on food frequency questionnaires in each study separately. The association between ADII and thyroid cancer risk was assessed using logistic regression models controlling for potential confounders. RESULTS: Higher ADII scores, corresponding to a higher pro-inflammatory potential of the diet, were associated with higher DTC risk (odds ratio (OR) for 1 standard deviation (SD) increase: 1.09, 95% confidence interval (CI): 1.01, 1.18, P: 0.03). Associations were stronger in analyses restricted to women (OR for 1-SD increase: 1.14, 95% CI 1.04, 1.25, P: 0.005), as well as in women with lower education level, current smoking, or high body mass index. CONCLUSION: Our study suggests that a pro-inflammatory diet is associated with an increased risk of DTC, especially when combined with other inflammatory conditions such as tobacco smoking or overweight. Our findings will help better understand the role of diet-induced inflammation in DTC etiology.

Diverging incidence trends of oral tongue cancer compared to other head and neck cancers in young adults in France.

While head and neck cancer incidence decreased worldwide due to reduced tobacco and alcohol consumption, oral tongue cancer (OTC) incidence has been reported to be increasing in several countries. Our study examines the incidence trends of OTC in France from 1990 to 2018, globally and by age; and compares the incidence trends with the evolution of the incidence of other human papilloma virus-unrelated head and neck squamous cell carcinoma, that is, cancers of the remaining subsites of the oral cavity (RSOCC) and laryngeal cancers for the period 1990 to 2018. World age-standardized incidence rates of oral tongue cancers (C02), cancers of the remaining subsites of the oral cavity (RSOCC, C03-06) and laryngeal cancers (C32) were estimated using the French National Network of Cancer Registries for the period 1990 to 2018. Trends in national incidence rates were estimated from a mixed-effect Poisson model including age and year effects using penalized splines and a district-random effect. In women aged 30 and 40, a significant increase in OTC incidence was observed, while ROSCC showed a nonsignificant incidence decrease. In young men aged 25, a marginally significant increase of OTC incidence years was observed, while incidence rates of RSOCC significantly declined. The results suggest a tendency towards diverging incidence trends for OTC compared to RSOCC and laryngeal cancer in young adults. The observed trends may reflect changes in underlying exposures or emerging exposures not yet identified, and stress the need to further investigate the etiology of oral tongue cancers.

Role of DNA Repair Variants and Diagnostic Radiology Exams in Differentiated Thyroid Cancer Risk: A Pooled Analysis of Two Case-Control Studies.

BACKGROUND: Given the increased use and diversity of diagnostic procedures, it is important to understand genetic susceptibility to radiation-induced thyroid cancer. METHODS: On the basis of self-declared diagnostic radiology examination records in addition to existing literature, we estimated the radiation dose delivered to the thyroid gland from diagnostic procedures during childhood and adulthood in two case-control studies conducted in France. A total of 1,071 differentiated thyroid cancer (DTC) cases and 1,188 controls from the combined studies were genotyped using a custom-made Illumina OncoArray DNA chip. We focused our analysis on variants in genes involved in DNA damage response and repair pathways, representing a total of 5,817 SNPs in 571 genes. We estimated the OR per milli-Gray (OR/mGy) of the radiation dose delivered to the thyroid gland using conditional logistic regression. We then used an unconditional logistic regression model to assess the association between DNA repair gene variants and DTC risk. We performed a meta-analysis of the two studies. RESULTS: The OR/mGy was 1.02 (95% confidence interval, 1.00-1.03). We found significant associations between DTC and rs7164173 in CHD2 (P = 5.79 × 10-5), rs6067822 in NFATc2 (P = 9.26 × 10-5), rs1059394 and rs699517 both in ENOSF1/THYS, rs12702628 in RPA3, and an interaction between rs7068306 in MGMT and thyroid radiation doses (P = 3.40 × 10-4). CONCLUSIONS: Our results suggest a role for variants in CDH2, NFATc2, ENOSF1/THYS, RPA3, and MGMT in DTC risk. IMPACT: CDH2, NFATc2, ENOSF1/THYS, and RPA3 have not previously been shown to be associated with DTC risk.

Gene network and biological pathways associated with susceptibility to differentiated thyroid carcinoma.

Variants identified in earlier genome-wide association studies (GWAS) on differentiated thyroid carcinoma (DTC) explain about 10% of the overall estimated genetic contribution and could not provide complete insights into biological mechanisms involved in DTC susceptibility. Integrating systems biology information from model organisms, genome-wide expression data from tumor and matched normal tissue and GWAS data could help identifying DTC-associated genes, and pathways or functional networks in which they are involved. We performed data mining of GWAS data of the EPITHYR consortium (1551 cases and 1957 controls) using various pathways and protein-protein interaction (PPI) annotation databases and gene expression data from The Cancer Genome Atlas. We identified eight DTC-associated genes at known loci 2q35 (DIRC3), 8p12 (NRG1), 9q22 (FOXE1, TRMO, HEMGN, ANP32B, NANS) and 14q13 (MBIP). Using the EW_dmGWAS approach we found that gene networks related to glycogenolysis, glycogen metabolism, insulin metabolism and signal transduction pathways associated with muscle contraction were overrepresented with association signals (false discovery rate adjusted p-value < 0.05). Additionally, suggestive association of 21 KEGG and 75 REACTOME pathways with DTC indicate a link between DTC susceptibility and functions related to metabolism of cholesterol, amino sugar and nucleotide sugar metabolism, steroid biosynthesis, and downregulation of ERBB2 signaling pathways. Together, our results provide novel insights into biological mechanisms contributing to DTC risk.

Fine-mapping of two differentiated thyroid carcinoma susceptibility loci at 2q35 and 8p12 in Europeans, Melanesians and Polynesians.

Differentiated thyroid carcinoma (DTC) incidence is characterized by wide ethnic and geographic variations, with high incidence rates observed in Oceanian populations. Genome-wide association studies (GWAS) identified mainly four DTC susceptibility loci at 9q22.33, 14q13.3, 2q35 and 8p12. Here we performed fine-mapping of the 2q35 and 8p12 loci in the population of the EPITHYR consortium that includes Europeans, Melanesians and Polynesians to identify likely causal variants for DTC risk. We conducted a colocalization analysis using eQTLs data to determine the SNPs with the highest probability of causality. At 2q35, we highlighted rs16857609 located in DIRC3. This SNP has a high probability of causality in the three populations, and a significant association in Europeans (OR = 1.4, p = 1.9 x 10-10). It is also associated with expression of DIRC3 and of the nearby gene IGFBP5 in thyroid tumour cells. At 8p12, we identified rs7844425 which was significantly associated with DTC in Europeans (OR = 1.32, p = 7.6 x 10-8) and rs2439304, which was highlighted by the colocalization analysis but only moderately associated with DTC in our dataset (OR = 1.2, p = 0.001). These SNPs are linked to the expression of NRG1 in thyroid tissue. Hence, our study identified novel variants at 2q35 and 8p12 to be prioritized for further functional studies.

Multiethnic genome-wide association study of differentiated thyroid cancer in the EPITHYR consortium.

Incidence of differentiated thyroid carcinoma (DTC) varies considerably between ethnic groups, with particularly high incidence rates in Pacific Islanders. DTC is one of the cancers with the highest familial risk suggesting a major role of genetic risk factors, but only few susceptibility loci were identified so far. In order to assess the contribution of known DTC susceptibility loci and to identify new ones, we conducted a multiethnic genome-wide association study (GWAS) in individuals of European ancestry and of Oceanian ancestry from Pacific Islands. Our study included 1554 cases/1973 controls of European ancestry and 301 cases/348 controls of Oceanian ancestry from seven population-based case-control studies participating to the EPITHYR consortium. All participants were genotyped using the OncoArray-500K Beadchip (Illumina). We confirmed the association with the known DTC susceptibility loci at 2q35, 8p12, 9q22.33 and 14q13.3 in the European ancestry population and suggested two novel signals at 1p31.3 and 16q23.2, which were associated with thyroid-stimulating hormone levels in previous GWAS. We additionally replicated an association with 5p15.33 reported previously in Chinese and European populations. Except at 1p31.3, all associations were in the same direction in the population of Oceanian ancestry. We also observed that the frequencies of risk alleles at 2q35, 5p15.33 and 16q23.2 were significantly higher in Oceanians than in Europeans. However, additional GWAS and epidemiological studies in Oceanian populations are needed to fully understand the highest incidence observed in these populations.

What is the most appropriate period to define synchronous cancers?

BACKGROUND: Studies about second primary cancers (SPC) incidence exclude a period following the first cancer diagnosis given the high probability of diagnosing another primary cancer during this phase (synchronous cancers). However, definition of synchronicity period varies widely, from one to six months, without clear epidemiological justification. The objective of this study was to determine the most appropriate synchronicity period. METHODS: Data from 13 French population-based cancer registries were used to establish a cohort of all patients diagnosed with a first cancer between 1989 and 2010. The incidence rate of subsequent cancer was computed by day within 1 year of follow-up after the first diagnosis. Incidence was modelized by joinpoint regression models with an initial quadratic trend and a second constant part (plateau). The joinpoint was the point from which the plateau began and defining the synchronicity period. RESULTS: Our cohort included 696,775 patients with a first cancer, of which 12,623 presented a SPC. The median joinpoint for all sites combined was estimated at 120.5 days [112.0-129.0]. Analysis by gender reported a higher difference in 32 days for males (127.8 vs 96.1 days). Noteworthy differences were found depending on patient age and the site of first cancer, with joinpoint ranging from 84.7 (oesophagus cancer) to 250.1 days (bladder cancer). CONCLUSION: Although some heterogeneity was observed based on the characteristic of the patients, the appropriate synchronicity period appears to be 4 months after the diagnosis of first cancer.

Cancer Among Adolescents and Young Adults Between 2000 and 2016 in France: Incidence and Improved Survival.

Purpose: This study was undertaken to determine cancer survival and describe the spectrum of cancers diagnosed among French adolescent and young adult (AYA) population. Methods: All cases of cancer diagnosed in 15-24 years, recorded by all French population-based registries (18% of the French population), over the 2000-2016 period, were included. Age-standardized incidence rates, conventional annual percentage change (cAPC) of incidence over time, and 5-year overall survival (5yOS) were calculated. Results: We analyzed 2734 cancer diagnoses in adolescents and 4199 in young adults. Overall incidence rates were 231.9/106 in 15-19 year olds and 354.0/106 in 20-24 year olds. The most frequently diagnosed cancers in male AYA were malignant gonadal germ-cell tumors (GCT), Hodgkin lymphoma (HL), and malignant melanoma and were HL, thyroid carcinoma, and malignant melanoma in females. Cancer incidence was stable over time with a cAPC of 0.8% (p = 0.72). For all cancers combined, 5yOS was 86.6% (95% CI: 85.8-87.4), >85% for HL, non-Hodgkin lymphomas (NHL), GCT, thyroid carcinomas, and malignant melanomas, and around 60% and lower for osteosarcomas, Ewing tumors, hepatic carcinomas, and rhabdomyosarcomas. The 5yOS has significantly improved from 2000-2007 to 2008-2015 for all cancers pooled, with a substantial gain of 4% for 15-19 year olds and 3% for 20-24 year olds. Conclusion: Notwithstanding the encouraging results for some cancers, and overall, persistent poorer survivals in AYA were shown compared to children for acute lymphoblastic leukemia, osteosarcoma, Ewing tumor, rhabdomyosarcoma, and malignant hepatic tumors. These disparities require further investigation to identify and address the causes of these inferior outcomes.

Evaluation of long-term living conditions in patients treated for localised prostate cancer.

PURPOSE: To evaluate the evolution of living conditions (LC) in long-term survivors of localised prostate cancer 10 years after treatment compared with those of a same-age control group from the general population. METHODS: Two hundred and eighty-seven patients diagnosed with prostate cancer in 2001 were selected in 11 French cancer registries. They were matched with controls randomly selected for age and residency. Both patients and controls completed a self-administered LC questionnaire concerning their familial, social and professional life, and general and specific quality of life (QoL) and anxiety and depression questionnaires. RESULTS: Compared with controls, patients reported more sexual modifications (p < .0001), but without any difference in marital status. Patients' circle of friends was more stable than that of the controls (91% vs. 63%; p < .0001) and patients reported fewer friendship modifications than controls (p < .0006). Their professional and physical activities were also preserved. They reported more anxiolytic intake (p = .002) but did not consult their general practitioner more often. Type of specialist consulted differed in the two groups. CONCLUSION: Patients treated for localised prostate cancer had the same living conditions as men of the same age. Their social life was satisfying on the whole, albeit they reported more sexual difficulties than their counterparts.

Progression of incidence and estimate of net survival from papillary thyroid cancers diagnosed between 2008 and 2016 in France.

BACKGROUND: After several decades of increasing incidence of papillary thyroid cancer (PTC), a change in this trend has been recently observed, particularly in the United States. This is attributed to the impact of new guidelines for the management of thyroid disease. The objective of this study was to describe the recent situation in France in terms of incidence and survival, taking account of tumor size. METHODS: Data from the FRANCIM network cancer registries, covering around 25% of the French metropolitan population, were analyzed. Distribution according to tumor size was determined in terms of frequency, trends in incidence and spatial distribution for the period 2008-2016. Analysis of net survival considered gender, age and tumor size. RESULTS: Cancers of size≤5mm were predominant in patients diagnosed between 55 and 74 years of age. Incidence of≤5mm tumors in women and of 5-10mm tumors in men began declining in the early 2010s. Incidence of 10-20mm and 20-40mm tumors in men increased significantly throughout the period 2008-2016. For both men and women, the incidence of the largest tumors (>40mm) also increased, but not significantly. The spatial distribution of incidence showed great heterogeneity. Net survival was generally high, although decreasing with age and tumor size. CONCLUSION: The recent epidemiological situation in France is consistent with the hypothesis of recent progress in medical management of thyroid pathologies. Variations in incidence should be monitored for both small (<10mm) and larger tumors, and notably>40mm tumors. Net survival is generally high, although decreasing with age and tumor size.

Analysis of medico-social factors for return to work among patients presenting with haematological malignancy (adamantine): results of a 'pilot study'.

OBJECTIVE: The aim of this study was to describe return to work determinants in patients with haematological malignancy. RESULTS: This medico-social pilot study included patients with haematological malignancy in the département of Calvados, aged 18 to 55 years, diagnosed between 1st January and 31st December 2010 and alive at 1st January 2015. Patients were identified via consultation of the Lower Normandy haematological malignancy Registry. They completed a specially developed self-questionnaire, in addition to validated questionnaires for anxiety-depression, quality of life and fatigue. Of the patients contacted, 50% accepted to participate. The mean age at diagnosis was 49.8 years, and the majority of patients (79.2%) was professionally active at the time of diagnosis. Only 64.9% of subjects had stopped work due to illness. The psychological impact (demonstrated anxiety) was significantly greater in men (p = 0.01). The majority of subjects returned to work after treatment (80.7%) and among them, the mean duration of absence from work was 16.1 months. Only 52.6% of subjects had informed their occupational physician and 56.7% had benefited from a pre-return visit. The satisfactory response rate obtained is promising for the extension of the present project as a prospective multicentric study.

Welding and the risk of head and neck cancer: the ICARE study.

OBJECTIVE: To investigate the association between occupational exposure to welding and the risk of head and neck cancer in a large French population-based case-control study, the Investigation of occupational and environmental CAuses of REspiratory cancers study. METHODS: Analyses were restricted to men (2703 controls and 1588 cases of squamous-cell carcinoma of the oral cavity, oropharynx, hypopharynx and larynx). Welding activity and potential confounders were assessed by detailed questionnaires. ORs and CIs (95% CI) were estimated by unconditional logistic regression, adjusted for age, area of residence, tobacco smoking, alcohol consumption and occupational exposure to asbestos. RESULTS: Welding was associated with an increased risk of head and neck cancer overall (OR=1.31, 95% CI 1.03 to 1.67). The association was strongest for laryngeal cancer (OR=1.66, 95% CI 1.15 to 2.38) and the risk increased with the cumulative duration (p-trend <0.01) and the weighted duration (p-trend <0.01) of welding. A cumulative duration and a weighted duration of welding of more than 10 years were also associated with a significantly increased risk of oral cancer (OR=1.82, 95% CI 1.09 to 3.04; OR=2.10, 95% CI 0.99 to 4.45, respectively). A long duration of arc welding was associated with laryngeal cancer, whereas a long duration of spot welding was associated with oral cancer. Welding was not associated with the risk of oropharyngeal and hypopharyngeal cancer. CONCLUSION: Our findings suggest that welding and several welding-related tasks increase the risk of laryngeal cancer and to a lesser extent oral cancer.

Role of GSTM1 and GSTT1 genotypes in differentiated thyroid cancer and interaction with lifestyle factors: Results from case-control studies in France and New Caledonia.

BACKGROUND: GSTM1 and GSTT1 are involved in detoxification of xenobiotics, products of oxidative stress and in steroid hormones metabolism. We investigated whether GSTM1 and GSTT1 gene deletion was associated with DTC risk and explored interaction with non-genetic risk factors of DTC. METHODS: The study included 661 DTC cases and 736 controls from two case-control studies conducted in France and New Caledonia. Odds ratios (OR) and their confidence interval (CI) for DTC associated with GST genotypes, alcohol drinking, tobacco smoking, body mass index and hormonal factors were calculated using logistic regression models. RESULTS: Results are presented for Europeans and Melanesians combined, as no heterogeneity between groups was detected. We found that DTC risk increased with obesity and decrease with alcohol drinking. After stratification by gene deletion status, the OR for obesity was 5.75, (95%CI 2.25-14.7) among individuals with GSTT1 and GSTM1-deleted genotype, and 1.26, (95%CI 0.89-1.77) in carriers of both genes (p-interaction = 0.02). The OR for drinking ≥1 glass/week was 0.33 (95%CI 0.15-0.74) in GSTT1-null individuals while it was 1.01 (95%CI 0.67-1.52) in non-null carriers of the gene (p-interaction = 0.01). No interaction between GST genotypes and other non-genetic risk factors was detected. CONCLUSION: GSTM1 and GSTT1 genotypes may modulate the DTC risk associated with BMI and alcohol consumption.

Occupational exposure to pesticides and multiple myeloma in the AGRICAN cohort.

PURPOSE: Epidemiological studies have found an increased risk of multiple myeloma (MM) in farmers. Few studies have investigated the detailed circumstances of occupational pesticide exposure which could explain these increased risks (pesticide use on crops, seeds or on animals, contact with treated crops) and the role of other exposures. In the Agriculture and Cancer cohort (AGRICAN), we assessed the associations between MM and crop- or animal-related activities, with specific attention to pesticide exposure via use on animals and crops or contact with treated crops and to disinfectant exposure. METHODS: Analyses concerned 155,192 participants, including 269 incident MM identified by cancer registries from enrolment (2005-2007) to 2013. Cox models using attained age as time scale were run to calculate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: MM risk was increased in farmers (i) who started using pesticides on crops in the 1960s, especially among those applying pesticides on corn (≥ 20 years: HR 1.73, 95% CI 1.08, 2.78, p for trend < 0.01) and (ii) using insecticides on animals (HR 1.48, 95% CI 1.11, 1.98), especially among horse farmers (≥ 10 years: HR 2.77, 95% CI 1.22-6.27, p for trend = 0.01). We also observed significant elevated risks with disinfectant use in animal barns. CONCLUSIONS: Findings support the role of pesticide use on crops and animals in the occurrence of MM risk in farmers.

The ongoing French metastatic breast cancer (MBC) cohort: the example-based methodology of the Epidemiological Strategy and Medical Economics (ESME).

PURPOSE: The currently ongoing Epidemiological Strategy and Medical Economics (ESME) research programme aims at centralising real-life data on oncology care for epidemiological research purposes. We draw on results from the metastatic breast cancer (MBC) cohort to illustrate the methodology used for data collection in the ESME research programme. PARTICIPANTS: All consecutive ≥18 years patients with MBC treatment initiated between 2008 and 2014 in one of the 18 French Comprehensive Cancer Centres were selected. Diagnostic, therapeutic and follow-up data (demographics, primary tumour, metastatic disease, treatment patterns and vital status) were collected through the course of the disease. Data collection is updated annually. FINDING TO DATE: With a recruitment target of 30 000 patients with MBC by 2019, we currently screened a total of 45 329 patients, and >16 700 patients with a metastatic disease treatment initiated after 2008 have been selected. 20.7% of patients had an hormone receptor (HR)-negative MBC, 73.7% had a HER2-negative MBC and 13.9% were classified as triple-negative BC (ie, HER2 and HR status both negative). Median follow-up duration from MBC diagnosis was 48.55 months for the whole cohort. FUTURE PLANS: These real-world data will help standardise the management of MBC and improve patient care. A dozen of ancillary research projects have been conducted and some of them are already accepted for publication or ready to be issued. The ESME research programme is expanding to ovarian cancer and advanced/metastatic lung cancer. Our ultimate goal is to achieve a continuous link to the data of the cohort to the French national Health Data System for centralising data on healthcare reimbursement (drugs, medical procedures), inpatient/outpatient stays and visits in primary/secondary care settings. TRIAL REGISTRATION NUMBER: NCT03275311; Pre-results.