Christine Lasset

Claude Bernard University Lyon 1, Villeurbanne, Rhône-Alpes, France

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Publications (173)1168.12 Total impact

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    ABSTRACT: Background: Mutations in BRCA1/2 confer a high risk of breast cancer (BC), but literature values of this risk vary. A genotype-phenotype correlation has been found in both genes and the effect of reproductive factors differs according to mutation location. We hypothesize that such a variation may exist for other factors related to estrogen exposure. Methods: We used a weighted Cox regression model to assess variation in BC risk with these factors using location of mutation in homogeneous BC risk region of BRCA1/2 in the GENEPSO study. Results: We found that late age at menarche reduced BC risk by 31% and that among BRCA1 carriers, a long or a short menstrual cycle increased risk (by 35% and 48%, respectively). Among premenopausal women, overweight was associated with a 39% decrease in BC risk while underweight was associated with an increased risk (hazard ratio [HR]=2.09). A natural menopause, mainly after age 50, was associated with a high BC risk (HR=2.46) and a significant interaction between menopause status and the location of mutations was found leading up to 10% variation in absolute risk according to the age at menopause. Conclusions: As observed in the general population, late menarche, long or short menstrual cycle, over- or under-weight, and being post-menopausal were associated with BC risk in BRCA1/2 carriers. The association with the menopause was observed only when the mutation was located in the "high-risk" zones. Impact: Taking into account modifier factors, location of mutation might be important for the clinical management of BRCA1/2 carriers. Copyright © 2015, American Association for Cancer Research.
    01/2015;
  • Journal of medical genetics. 01/2015;
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    ABSTRACT: For carriers of germline mutations in DNA mismatch repair genes, the most relevant statistic for cancer prevention is colorectal cancer (Lynch syndrome) risk, particularly in the short term. We conducted a meta-analysis of all independent published Lynch syndrome studies reporting age- and sex-dependent colorectal cancer risks. We estimated 5-year colorectal cancer risk over different age groups, separately for male and female mutation carriers, and number needed to screen to prevent one death. We pooled estimates from analyses of 1,114 Lynch syndrome families (508 with MLH1 mutations and 606 with MSH2 mutations). On average, one in 71 male and one in 102 female MLH1 or MSH2 mutation carriers in their 20s will be diagnosed with colorectal cancer in the next 5 years. These colorectal cancer risks increase with age, peaking in the 50s (one in seven males and one in 12 females), and then decrease with age (one in 13 males and one in 19 females in their 70s). Annual colonoscopy in 16 males or 25 females in their 50s would prevent one death from colorectal cancer over 5 years while resulting in almost no serious complications. In comparison, annual colonoscopy in 155 males or 217 females in their 20s would prevent one death while resulting in approximately one serious complication. For MLH1 or MSH2 mutation carriers, current guidelines recommend colonoscopy every 1 to 2 years starting in their 20s. Our findings support this regimen from age 30 years; however, it might not be justifiable for carriers who are in their 20s. © 2014 by American Society of Clinical Oncology.
    Journal of Clinical Oncology 12/2014; · 17.88 Impact Factor
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    ABSTRACT: Background Due to underestimation, surgical excision is recommended for atypical ductal hyperplasia (ADH) diagnosed on directional vacuum-assisted biopsies (DVAB). The following guidelines have been established according to our retrospective study published in 2008: excision for lesions ≥ 21 mm, follow-up for lesions < 6 mm with complete removal of microcalcifications, follow-up or excision for 6-21 mm lesions with respectively less or more than 2 ADH foci. Methods and Results These guidelines were assessed in a prospective series of 124 patients with a median follow-up of 30 months. Conformity rate was 92%. Upgrading was 28% (15 patients out of 53) for conformed surgery and absent for surgery performed beyond the scope of guidelines. For the patients with benign surgery (n=38) or just followed (n=61), 3 cancers occurred in either breast at 1 to 3 years. Conclusions These convenient guidelines can safely spare surgery for a subset of patients. However, annual mammographic follow-up is recommended since the risk of subsequent cancer remains high for both breasts.
    American journal of surgery 08/2014; · 2.36 Impact Factor
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    ABSTRACT: Purpose:This study aimed to measure patients' smoking patterns for 5 years after BRCA1/2 test result disclosure.Methods:A national cohort consisting of 621 French cancer-free women from families with BRCA1/2 mutations (mean age (SD): 40.5 years (11.5 years)) were included from December 1999 to January 2006, before disclosure of genetic test results, and followed for 5 years. They completed self-administered questionnaires about their cigarette smoking behaviors before receiving their test results (baseline) and 6, 12, 24, and 60 months after disclosure. Multivariate statistical analyses of the changes in participants' smoking behaviors were performed using a zero-inflated Poisson mixed model.Results:Baseline smoking was found to depend on age, educational level, marital status, alcohol consumption, body mass index, and cancer risk perception. The zero-inflated part of the model showed the occurrence of no significant changes in the percentage of smokers during the 5 years after disclosure of the BRCA1/2 test results; however, daily smoking among BRCA1/2 carriers decreased significantly compared with that of noncarriers (adjusted hazard ratio = 0.83; (95% confidence interval: 0.69-0.99); P = 0.04) after adjusting for baseline smoking behavior.Conclusion:It would be worth investigating the possibility of counseling women during the genetic testing process about the multiple risk factors involved in cancer, such as genetic and lifestyle factors.Genet Med advance online publication 10 July 2014Genetics in Medicine (2014); doi:10.1038/gim.2014.82.
    Genetics in medicine: official journal of the American College of Medical Genetics 07/2014; 17(2). · 3.92 Impact Factor
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    ABSTRACT: Although greater attention is currently being paid to participants in research, no studies have dealt so far with the issue of returning aggregate psychosocial results to cohort participants.
    Health expectations: an international journal of public participation in health care and health policy 05/2014; · 1.80 Impact Factor
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    ABSTRACT: To use both quantitative and qualitative methods to investigate the evolution of practices and opinions regarding human papillomavirus (HPV) vaccination among French general practitioners. A cross-sectional study (self-questionnaires) was performed in 2007 and repeated in 2010 among 271 general practitioners. Semi-structured interviews were conducted on 27 voluntary participants by a sociologist and analyzed according to content analysis. Acceptability of HPV vaccination had increased from 2007 to 2010 (79.9 vs. 87.1 %, respectively), just as the practice of HPV vaccination among 14-year-old girls (19.0 vs. 49.1 %, respectively). Though about 60 % reported complications associated with HPV vaccination, irrespective of year, the types of difficulties have varied: difficulties related to "questions asked by patients" had decreased, though concerns about side effects had remained stable. During interviews, difficulties related to "the reason for medical consultation" and "the target age" were often associated with addressing the issue of sexuality, especially when the parents were present. Although the high level of acceptability of HPV vaccination among general practitioners, which increased from 2007 to 2010, there remain difficulties in addressing this practice.
    International Journal of Public Health 04/2014; 59(3). · 1.99 Impact Factor
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    ABSTRACT: We aimed to study the relationships between educational level, women's knowledge about cervical cancer (CC), and acceptance of HPV vaccination for their daughters.
    PLoS ONE 01/2014; 9(10):e109320. · 3.53 Impact Factor
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    ABSTRACT: The aim of this study is to prospectively determine the factors contributing to whether unaffected women from BRCA1/2 families reported that clinicians proposed psychological consultations and that they had attended these consultations during the genetic testing process. A prospective study was performed on a national cohort, using self-administered questionnaires to determine the rates of proposal and use of psychological services at the time of BRCA1/2 test result disclosure (N = 533) and during the first year after disclosure (N = 478) among unaffected French women from BRCA1/2 families who had undergone genetic testing for BRCA1/2. Multivariate adjustment was carried out using logistic regression models fitted using generalized estimation equations, with the genetic testing centre as the clustering variable. At the time of BRCA1/2 test result disclosure, a psychological consultation was proposed by cancer geneticists to 72% and 32% of the carriers (N = 232) and noncarriers (N = 301), respectively (p < 0.001). One year after disclosure, 21% of the carriers had consulted a psychologist, versus 9% of the noncarriers (p < 0.001). Both the proposal and the uptake depended on the women's BRCA1/2 mutation carrier status (proposal adjusted odds ratio (AOR): 4.9; 95% confidence interval (CI) 3.4-7.2; uptake AOR: 2.2; 95% CI 1.2-4.0), their level of education (proposal AOR: 1.7; 95% CI 1.1-2.7; uptake AOR: 4.5; 95% CI 1.7-12.1) and the distress they experienced about their genetic test results (proposal AOR: 1.02; 95% CI 1.01-1.03; uptake AOR: 1.04; 95% CI 1.02-1.06) CONCLUSIONS: Determinants of the proposal/uptake of psychological consultations in the BRCA1/2 testing process highlight the need for inventive strategies to reach the different types of women's profiles. Copyright © 2013 John Wiley & Sons, Ltd.
    Psycho-Oncology 10/2013; 23(4). · 4.04 Impact Factor
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    ABSTRACT: To help prevent cervical cancer, three yearly opportunistic Pap smear screening is recommended in France for women aged 25-65 years. Pap smear screening coverage varies with age and socioeconomic level. The aim of this cross-sectional study was to identify factors associated with a low uptake of Pap smear screening among women with no limited access to healthcare. We analyzed data from women aged 25-65 living in the Rhône-Alpes region who completed a self-administered questionnaire given to them by general practitioners between June and August 2008. The questionnaire covered knowledge about cervical cancer and its prevention as well as the women's history of Pap smear screening and other health-related behaviors. The relationship between low uptake of Pap smear screening - defined as not having had the test within the past 3 years - and a range of possible contributing factors was investigated using logistic regression. Of 1186 women with an intact uterus who completed the questionnaire, 89.1% said they had had a Pap smear within the past 3 years. On multivariate analysis, the 10.9% who had not were significantly more likely to live alone (1.76 [1.13-2.74]), to have no children (2.17 [1.31-3.62]), to have never used contraception (5.35 [2.98-9.62]), to have less knowledge about Pap smear screening (3.40 [1.55-7.49]), and to be unvaccinated against hepatitis B (0.55 [0.35-0.87]). Despite high overall compliance with Pap smear screening recommendations among women who consulted general practitioners, several factors were significantly associated with a low uptake of the service. Considering these factors may help to refine messages aimed at cervical cancer prevention.
    Revue d Épidémiologie et de Santé Publique 09/2013; · 0.66 Impact Factor
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    ABSTRACT: HPV vaccination is recommended in France for girls aged 14 and for those aged 15-23 before sexual debut or who have become sexually active within the previous year. The first aim was to describe vaccination practice among 14-23-year-old girls visiting a general practitioner. A second objective was to investigate factors associated with starting vaccination among girls aged 14-18, in particular the regular practice of Pap-smear screening (PSS) by their mothers. A cross-sectional study was conducted from June to August 2009. A total of 87 general practitioners from the large Rhône-Alpes region contributed data on 502 girls/women who came for consultation. 231 (46.0%) of these girls/women had begun the process of HPV vaccination (68.2%, 56.9% and 18.7% of the 14-16, 17-20 and 21-23-year-olds respectively) of whom 139 (60.2%) had received all three doses. 92 girls/women (39.8%) had received only one or two doses at the time of study. However, in 71 (30.7%) cases, the gap between the last dose received and the time of study was within the between-dose interval recommended in the vaccination schedule. GPs reported that 16 (11.5%) had mentioned side effects following injections. Having a mother who practised regular PSS (Odds Ratio 6.2 [1.5-25.8]), having never lived with a partner (4.6 [1.6-13.5]) and vaccination against hepatitis B (3.2 [1.6-6.1]) were found to be independently correlated with the initiation of HPV vaccination among girls/women aged 14-18 years. Two years after the start of the programme, only half of girls/women aged 14-23 years had begun the process of HPV vaccination. HPV vaccination status was correlated with PSS in the mother, family status and hepatitis B vaccination. Such information may help to better target girls who are less likely to be vaccinated.
    Vaccine 09/2013; · 3.49 Impact Factor
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    ABSTRACT: Based on nationwide data from the French national cancer institute (INCa), we analyzed the evolution of cancer genetics consultations and testing over time, and the uptake of targeted tests in relatives of families with BRCA1/2 or MMR genes mutation. Genetic testing and consultations for familial high-risk individuals are exclusively funded and monitored by the INCa in France. All nationwide cancer genetics centers reported annually standardized parameters of activity from 2003 to 2011. The analysis included a total of 240,134 consultations and 134,652 genetic tests enabling to identify 32,494 mutation carriers. Referral for hereditary breast and ovarian cancer (HBOC) or colorectal cancer predisposition syndromes represented 59 % (141,639) and 23.2 % (55,698) consultations, respectively. From 2003 to 2011, we found a dramatic and steady increase of tests performed for BRCA1/2 (from 2,095 to 7,393 tests/year, P < 0.0001) but not for MMR genes (from 1,144 to 1,635/year, P = NS). The overall percentage of deleterious mutations identified in the probands tested was 13.8 and 20.9 % in HBOC and Lynch syndromes, respectively. Pooled analysis for BRCA1/2 and Lynch syndrome tests showed an inverse relationship between the percentage of mutation detected and the absolute number of tests performed over the time (overall Cochran-Armitage test for trend: P < 0.001). In families with BRCA1/2 or MMR identified mutations, there was an average number of 2.94 and 3.28 relatives performing targeted tests, respectively. This nationwide study shows a lack of referral and genetic testing in Lynch as compared to HBOC syndromes. Only a third of relatives of a proband with a predisposing mutation performed a targeted test. Enhanced information about benefit of genetic testing should be given to clinicians and patients for Lynch syndrome and relatives of a proband carrying an identified predisposing mutation.
    Breast Cancer Research and Treatment 08/2013; 141(1). · 4.47 Impact Factor
  • Journal of Clinical Oncology 04/2013; · 17.88 Impact Factor
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    ABSTRACT: Germline alterations of the tumour suppressor TP53 gene are detected approximately in 25% of the families suggestive of Li-Fraumeni syndrome (LFS), characterised by a genetic predisposition to a wide tumour spectrum, including soft-tissue sarcomas, osteosarcomas, premenopausal breast cancers, brain tumours, adrenocortical tumours, plexus choroid tumours, leukaemia and lung cancer. The aim of this study was to determine the contribution of germline copy number variations (CNVs) to LFS in families without detectable TP53 mutation. Using a custom-designed high-resolution array CGH, we evaluated the presence of rare germline CNVs in 64 patients fulfilling the Chompret criteria for LFS, but without any detectable TP53 alteration. In 15 unrelated patients, we detected 20 new CNVs absent in 600 controls. Remarkably, in four patients who had developed each brain tumour, the detected CNV overlap the KDM1A, MTA3, TRRAP or SIRT3 genes encoding p53 partners involved in histone methylation or acetylation. Focused analysis of SIRT3 showed that the CNV encompassing SIRT3 leads to SIRT3 overexpression, and that in vitro SIRT3 overexpression prevents apoptosis, increases G2/M and results in a hypermethylation of numerous genes. This study supports the causal role of germline alterations of genes involved in chromatin remodelling in genetic predisposition to cancer and, in particular, to brain tumours.European Journal of Human Genetics advance online publication, 24 April 2013; doi:10.1038/ejhg.2013.68.
    European journal of human genetics: EJHG 04/2013; · 3.56 Impact Factor
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    ABSTRACT: BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10(-8), HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10(-8), HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10(-8), HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific association. The 17q21.31 locus was also associated with ovarian cancer risk in 8,211 BRCA2 carriers (P = 2×10(-4)). These loci may lead to an improved understanding of the etiology of breast and ovarian tumors in BRCA1 carriers. Based on the joint distribution of the known BRCA1 breast cancer risk-modifying loci, we estimated that the breast cancer lifetime risks for the 5% of BRCA1 carriers at lowest risk are 28%-50% compared to 81%-100% for the 5% at highest risk. Similarly, based on the known ovarian cancer risk-modifying loci, the 5% of BRCA1 carriers at lowest risk have an estimated lifetime risk of developing ovarian cancer of 28% or lower, whereas the 5% at highest risk will have a risk of 63% or higher. Such differences in risk may have important implications for risk prediction and clinical management for BRCA1 carriers.
    PLoS Genetics 03/2013; 9(3):e1003212. · 8.17 Impact Factor
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    ABSTRACT: BACKGROUND: Having been vaccinated against the human papilloma virus (HPV) may affect other behaviours related to sexual health. This study assessed knowledge and behaviour relevant to the prevention of sexually transmitted infections (STIs) among girls/women aged 14-23 years in relation to their HPV vaccination status. METHODS: From November 2008 to February 2009, 328 girls/women from the Rhône-Alpes region were recruited by general practitioners and completed a self-administered questionnaire. RESULTS: In all, 316 of the 328 respondents provided information on their HPV vaccination status: 135 (42.7%) had been vaccinated (51.2% of girls aged 14-16 years, 44% of women aged 17-20 years and 18.9% of 21-23-year-olds). Knowledge about HPV and the Pap smear was poor overall but greater in those who had been vaccinated: vaccinated 14-16-year-olds were significantly more likely to know the aim of the Pap smear than those not vaccinated (72.7% vs. 41.3%, P < 0.001), and vaccinated 21-23-year-olds were more likely to know about the need to continue Pap smear screening, despite vaccination (60.0% vs. 25.6%, P = 0.06). Irrespective of vaccination status, >80% cited condoms as a means of STI prevention and >85% of those who were sexually active used them. No difference was observed between vaccinated and non-vaccinated groups regarding requests for HIV serology, history of abortions or emergency hormonal contraception. CONCLUSION: Knowledge about cervical cancer prevention was better among those who had been vaccinated against HPV than among those who had not. Knowledge and behaviour relevant to STI prevention seemed appropriate whatever the respondents' vaccination status.
    The European Journal of Public Health 02/2013; · 2.52 Impact Factor
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    ABSTRACT: BACKGROUND: In France, it is recommended that girls and women aged 14--23 are vaccinated against the human papillomavirus (HPV). However, French women's knowledge of and attitude towards the vaccine has been little studied. METHODS: Thirty-nine general practitioners, representative of those working in the large Rhone-Alpes region, offered a self-administered questionnaire on cervical cancer (CC) prevention to all 18--65 year-old women who came for consultation during June and July 2008. In addition, semi-structured interviews were undertaken with a sample of those who had daughters aged 14--18. RESULTS: Of the 1,478 women who completed the questionnaire, only 16.9% mentioned HPV as the cause of CC, even though 76.2% knew of the vaccine. 210 women had daughters aged 14--18, and 32 were interviewed. Compared with the wider group, more of these women were aware of the HPV vaccine (91.4%). 44.8% knew the target population and 17.1% the recommended ages for vaccination. 54.3% favoured HPV vaccination; 37.2% were undecided and only 0.9% were opposed. The main barrier to acceptance was the recency of the vaccine's introduction and concern about possible side effects (54.9%); 14.1% preferred to rely on their GP's decision. Factors associated with acceptance of the HPV vaccine were having previously vaccinated a child against pneumococcus (OR=3.28 [1.32-8.11]) and knowing the target population for HPV vaccination (OR=2.12 [1.15-3.90]). Knowing the recommended frequency of Papanicolaou smear testing (Pap test) screening was associated with lower acceptance (OR=0.32 [0.13-0.82]). CONCLUSIONS: Few mothers are opposed to HPV vaccination. Factors associated with acceptability were knowledge about the vaccine, acceptance of other vaccines and, unexpectedly, lack of knowledge about the recommended frequency of Pap testing. On multivariate analysis, compliance with recommendations for Pap test screening and socioeconomic factors had no effect on views about HPV vaccination. Given that concern about possible side effects is the major barrier to wider acceptance of the HPV vaccine in France, GPs have a key role in providing information.
    BMC Public Health 11/2012; 12(1):1034. · 2.32 Impact Factor
    This article is viewable in ResearchGate's enriched format
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    ABSTRACT: OBJECTIVE: To estimate the risk of breast cancer associated with diagnostic radiation in carriers of BRCA1/2 mutations. DESIGN: Retrospective cohort study (GENE-RAD-RISK). SETTING: Three nationwide studies (GENEPSO, EMBRACE, HEBON) in France, United Kingdom, and the Netherlands, PARTICIPANTS: 1993 female carriers of BRCA1/2 mutations recruited in 2006-09. MAIN OUTCOME MEASURE: Risk of breast cancer estimated with a weighted Cox proportional hazards model with a time dependent individually estimated cumulative breast dose, based on nominal estimates of organ dose and frequency of self reported diagnostic procedures. To correct for potential survival bias, the analysis excluded carriers who were diagnosed more than five years before completion of the study questionnaire. RESULTS: In carriers of BRCA1/2 mutations any exposure to diagnostic radiation before the age of 30 was associated with an increased risk of breast cancer (hazard ratio 1.90, 95% confidence interval 1.20 to 3.00), with a dose-response pattern. The risks by quarter of estimated cumulative dose <0.0020 Gy, ≥0.0020-0.0065 Gy, ≥0.0066-0.0173 Gy, and ≥0.0174 Gy were 1.63 (0.96 to 2.77), 1.78 (0.88 to 3.58), 1.75 (0.72 to 4.25), and 3.84 (1.67 to 8.79), respectively. Analyses on the different types of diagnostic procedures showed a pattern of increasing risk with increasing number of radiographs before age 20 and before age 30 compared with no exposure. A history of mammography before age 30 was also associated with an increased risk of breast cancer (hazard ratio 1.43, 0.85 to 2.40). Sensitivity analysis showed that this finding was not caused by confounding by indication of family history. CONCLUSION: In this large European study among carriers of BRCA1/2 mutations, exposure to diagnostic radiation before age 30 was associated with an increased risk of breast cancer at dose levels considerably lower than those at which increases have been found in other cohorts exposed to radiation. The results of this study support the use of non-ionising radiation imaging techniques (such as magnetic resonance imaging) as the main tool for surveillance in young women with BRCA1/2 mutations.
    BMJ (online) 09/2012; 345:e5660. · 16.38 Impact Factor
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Publication Stats

4k Citations
1,168.12 Total Impact Points

Institutions

  • 2012–2015
    • Claude Bernard University Lyon 1
      Villeurbanne, Rhône-Alpes, France
  • 1988–2015
    • Centre Léon Bérard
      Lyons, Rhône-Alpes, France
  • 2009–2014
    • University of Lyon
      Lyons, Rhône-Alpes, France
  • 2013
    • McGill University
      Montréal, Quebec, Canada
  • 2003–2013
    • French National Centre for Scientific Research
      • Laboratoire de Biométrie et Biologie Évolutive (LBBE)
      Lutetia Parisorum, Île-de-France, France
  • 2011
    • Cancer Research Center of Lyon
      Lyons, Rhône-Alpes, France
    • University of Nice-Sophia Antipolis
      Nice, Provence-Alpes-Côte d'Azur, France
  • 2007
    • Institut de Cancérologie Gustave Roussy
      • Department of Radiotherapy
      Île-de-France, France
  • 2006
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
  • 2005
    • International Agency for Research on Cancer
      Lyons, Rhône-Alpes, France
  • 2002
    • Institut Paoli Calmettes
      • Cancer Research Center of Marseille (CRCM)
      Marsiglia, Provence-Alpes-Côte d'Azur, France
  • 1995
    • CHU de Lyon - Groupement Hospitalier Edouard Herriot
      Lyons, Rhône-Alpes, France
  • 1992
    • Université Libre de Bruxelles
      • Bordet Institute
      Bruxelles, Brussels Capital Region, Belgium