Sainte-Foy-lès-Lyon, France
Sainte-Foy-lès-Lyon, France

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Prada D.,Harvard University | Prada D.,Unidad University | Prada D.,National University of Costa Rica | Colicino E.,Harvard University | And 14 more authors.
BMC Psychiatry | Year: 2014

Background: APOE is the biomarker with the greatest known influence on cognitive function; however, the effect of complex haplotypes involving polymorphisms rs449647, rs405509, rs440446, rs429358 and rs7412 has never been studied in older populations. Methods: We evaluated APOE polymorphisms using multiplex PCR for genotyping and Mini-Mental State Examination (MMSE) to evaluate cognitive function in 819 individuals from VA Normative Aging Study.Results: Combinatorial analysis of all polymorphisms and individual analysis of polymorphisms rs449647, rs405509, rs440446 and rs7412 did not show any association with cognitive performance. Polymorphism rs429358 was associated with better cognitive performance (odds of MMSE ≤ 25 = 0.63, 95% CI 0.42-0.95; p = 0.03) in the oldest subsample (5th quintile of age) (odds of MMSE ≤ 25 = 0.34; 95% CI 0.13-0.86; p = 0.02). APOE allele ε4 was also associated with better cognitive performance (odds of MMSE ≤ 25 = 0.61, 95% CI 0.40-0.94; p = 0.02), also in the oldest subsample (odds of MMSE ≤ 25 = 0.35, 95% CI 0.14-0.90; p = 0.03). Conclusions: These results suggest a beneficial effect of polymorphism rs429358 in the oldest men. © 2014 Prada et al., licensee BioMed Central Ltd.


Decoster L.,Vrije Universiteit Brussel | Van Puyvelde K.,Vrije Universiteit Brussel | Mohile S.,University of Rochester | Wedding U.,Jena University Hospital | And 14 more authors.
Annals of Oncology | Year: 2015

Based on a systematic literature review, the screening tools task force of SIOG states that screening tools do not replace geriatric assessment in older cancer patients. However, in a busy clinical practice the use of such a tool is recommended to identify those patients in need of further evaluation and multidisciplinary approach. Further research remains necessary. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.


Bonnefoi H.,French Institute of Health and Medical Research | Jacot W.,Center Val urelle Paul Lamarque | Saghatchian M.,Gustave Roussy | Moldovan C.,Center Henri Becquerel | And 15 more authors.
Annals of Oncology | Year: 2015

Five trials assessed lapatinib and trastuzumab (L+T) combined with paclitaxel-containing chemotherapy regimens. They showed high pathological complete response rates, but at the cost of toxicity. This trial assesses L+T combined with docetaxel. The use of docetaxel rather than paclitaxel does not avoid much of the toxicity. Regarding efficacy our results are very consistent with NSABP-B41 trial. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.


Be ranger R.,Center Le on Be rard | Be ranger R.,International Agency for Research on Cancer IARC | Be ranger R.,University Claude Bernard Lyon 1 | Pe rol O.,Center Le on Be rard | And 10 more authors.
BMC Cancer | Year: 2014

Background: The incidence of testicular germ cell tumors (TGCT), the most common cancer in men aged 15 to 45 years, has doubled over the last 30 years in developed countries. Reasons remain unclear but a role of environmental factors, especially during critical periods of development, is strongly suspected. Reliable data on environmental exposure during this critical time period are sparse. Little is known on whether it could be a combined effect of early and later-life exposures.Methods/Design: Our research aims to study the association between TGCT risk and pesticide exposures (domestic, occupational and environmental) during critical time periods of development and combined early and later-life exposures. The study design, developed during a 2-year pilot study, is a multicenter case-control study of 500 cases (ascertained through histology) and 1000 fertile/fecund controls recruited through 21 French 'Centres d'Etude et de Conservation des Œufs et de Sperme humain' (CECOS). Trained professional interviewers interview the subjects and their mothers by phone. Using a geographic information system developed and tested for application in this study design, environmental pesticides exposure assessment is based on life-time residential history. Occupational pesticides exposures are assessed by an industrial hygienist based on parents' occupations and tasks. Exposures during the prenatal period, early childhood and puberty are focused. A blood sample is collected from each participant to assess genetic polymorphisms known to be associated with TGCT risk, as well as to explore gene-environment interactions.Discussion: The results of our study will contribute to better understanding the causes of TGCT and the rapid increase of its incidence. We explore the effect of combined early and later-life pesticides exposure from multiple sources, as well as potential gene-environment interactions that have until now been rarely studied for TGCT. Our design allows future pooled studies and the bio-bank allows additional genetic or toxicological analyses. © 2014 Be´ranger et al.; licensee BioMed Central Ltd.


Beuselinck B.,University Hospitals Leuven | Beuselinck B.,French Institute of Health and Medical Research | Karadimou A.,French Institute of Health and Medical Research | Lambrechts D.,Catholic University of Leuven | And 21 more authors.
British Journal of Cancer | Year: 2013

Background:There are no validated markers that predict response in metastatic renal cell cancer (RCC) patients treated with sunitinib. We aim to study the impact of single-nucleotide polymorphisms (SNPs) that have recently been proposed as predictors of outcome to anti-VEGF-targeted therapy in metastatic RCC in an independent cohort of patients.Methods:We genotyped 16 key SNPs in 10 genes involved in sunitinib pharmacokinetics, pharmacodynamics and VEGF-independent angiogenesis in patients with metastatic clear-cell RCC treated with sunitinib as the first-line targeted therapy. Association between SNPs, progression-free survival (PFS) and overall survival (OS) were studied by multivariate Cox regression using relevant clinical factors associated with PFS and OS as covariates.Results:In a series of 88 patients, both PFS and OS were associated significantly with SNP rs1128503 in ABCB1 (P=0.027 and P=0.025), rs4073054 in NR1/3 (P=0.025 and P=0.035) and rs307821 in VEGFR3 (P=0.032 and P=0.011). Progression-free survival alone was associated with rs2981582 in FGFR2 (P=0.031) and rs2276707 in NR1/2 (P=0.047), whereas OS alone was associated with rs2307424 in NR1/3 (P=0.048) and rs307826 in VEGFR3 (P=0.013).Conclusion: Our results confirm former communications regarding the association between SNPs in ABCB1, NR1/2, NR1/3 and VEGFR3 and sunitinib outcome in clear-cell RCC. Prospective validation of these SNPs is now required. © 2013 Cancer Research UK.


Julian-Reynier C.,French Institute of Health and Medical Research | Julian-Reynier C.,Aix - Marseille University | Mancini J.,French Institute of Health and Medical Research | Mancini J.,Aix - Marseille University | And 10 more authors.
European Journal of Human Genetics | Year: 2011

In a French national cohort of unaffected females carriers/non-carriers of a BRCA1/2 mutation, long-term preventive strategies and breast/ovarian cancer risk perceptions were followed up to 5 years after test result disclosure, using self-administered questionnaires. Response rate was 74%. Carriers (N=101) were younger (average age±SD=37±10) than non-carriers (N=145; 42±12). There were four management strategies that comprised 88% of the decisions made by the unaffected carriers: 50% opted for breast surveillance alone, based on either magnetic resonance imaging (MRI) and other imaging (31%) or mammography alone (19%); 38% opted for either risk reducing salpingo-oophorectomy (RRSO) and breast surveillance, based on MRI and other imaging (28%) or mammography alone (10%). The other three strategies were: risk reducing mastectomy (RRM) and RRSO (5%), RRM alone (2%) and neither RRM/RRSO nor surveillance (6%). The results obtained for various age groups are presented here. Non-carriers often opted for screening despite their low cancer risk. Result disclosure increased carriers' short-term high breast/ovarian cancer risk perceptions (P≤0.02) and decreased non-carriers' short- and long-term perceptions (P<0.001). During follow-up, high breast cancer risk perceptions increased with time among those who had no RRM and decreased in the opposite case; high ovarian cancer risk perceptions increased further with time among those who had no RRSO and decreased in the opposite case; RRSO did not affect breast cancer risk perceptions. Informed decision-making involves letting women know whether opting for RRSO and breast MRI surveillance is as effective in terms of survival as RRM and RRSO. © 2011 Macmillan Publishers Limited All rights reserved. © 2011 Macmillan Publishers Limited.

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