- Email: [email protected]
Sarcopenia is prevalent in more than half of older and younger patients with cancer
2013 SIOG Poster Abstracts
Track 2 - Haem malignancies in the elderly Lymphoma in the elderly P083 Non-anthracycline and dose-attenuated immunochemotherapy regimen (R-daCVP) in frail and highly elderly patients older than 70 years with later stage of diffuse large B-cell lymphoma J.H. Lim1,*, C.S. Kim2, Y.H. Park1, H.G. Yi1, J.C. Kim1, M.H. Lee1. 1 Internal Medicine; 2Inha University School of Medicine, INCHEON, Korea, Republic Of Introduction: Combination chemotherapy of R-CHOP is the standard treatment for patients with diffuse large B-cell lymphoma (DLBL) even in elderly patients. Patients with DLBL who are elderly and have poor performance status (≥ ECOG PS 2) are difficult to treat with a full course of R-CHOP therapy. Objectives: We have tried to treat these advanced and poor performance status of elderly DLBL patients with rituximab and dose attenuated chemotherapy without anthracycline. (R-daCVP) We retrospectively evaluated the efficacy and safety of the R-daCVP chemotherapy in these patients. Methods: From January 1, 2005 to December 31, 2011, newly diagnosed stage III-IV DLBL patients who were considered inappropriate to receive standard R-CHOP chemotherapy were enrolled in this study. The inclusion criteria of our study were as follows; diagnosis of DLBL that was confirmed by histological examination in patients aged ≥70 years and poor performance status (PS) (ECOG PS ≥2). Patients received rituximab 375 mg/m2 on day 1 of each cycle. Dose attenuated CVP consisted of cyclophosphamide 600 mg/m2 and vincristine 1 mg/ m2 (maximum 2 mg) that were given intravenously on day 1 and oral prednisolone 80 mg on days 1–5. The treatment was repeated every 3 weeks and it was continued for six or eight cycles, with withdrawal due to toxicity or disease progression. Chemotherapy dose modification was done by assessment of toxicities according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0. Results: We finally analyzed 13 patients. The median age was 78 years (range, 71-82). The distribution of the ECOG performance status was as follows: five patients (38.5%) with a performance status of 2, 8 patients (61.5%) with a performance status of 3. Eight patients (61.5%) were stage IV. Only 3 patients showed complete responses. Severe and fatal toxicity was significantly higher among these patients treated with even this less aggressive therapy. Four patients died due to grade 4 hematologic toxicities (grade 4 thrombocytopenia and grade 4 febrile neutropenia). Conclusion: In our study, we could not demonstrate that nonanthracycline dose attenuated combination immunochemotherapy with rituximab may have good potential in elderly DLBL patients with a poor PS. Eldely patients tend to have lower haemoglobin, leukocyte and platelet levels and may suffer greater toxicity from myelosuppressive chemotherapy. Careful toxicity monitoring and controlling the dose intensity or density may be needed in these fragile patients. Further studies are clearly warranted to identify the optimal management strategies for fragile and elderly patients with advanced DLBL.
S61
Verheul1. 1Medical Oncology; 2Nutrition and Dietetics; 3Geriatrics and Gerontology, VU University Medical Center, Amsterdam, Netherlands Introduction: In patients with cancer, sarcopenia (low skeletal muscle mass) and low muscle attenuation (increased proportion of inter- and intramuscular fat) are associated with increased toxicity. The prevalence of sarcopenia increases with age in the healthy population, but it is unclear whether sarcopenia is more prevalent in older compared to younger patients with cancer. Objectives: To study the prevalence of sarcopenia and low muscle attenuation in patients ≥65 years compared to patients b65 years with advanced cancer. Methods: In patients with advanced cancer (colorectal, breast- or prostate) weight, height and BMI were assessed before start of standard chemotherapy. Skeletal muscle mass and muscle attenuation were measured at the third lumbar vertebra with SliceOmatic software (v5.0) on CT images. Sarcopenia and low muscle attenuation were defined according to the sex- and BMI specific threshold values associated with low survival by Martin et al. Patients were divided into 2 age-groups (b65 and ≥65) to assess whether differences in the prevalence of sarcopenia and low muscle attenuation are present. Results: Data were obtained from 97 patients (59% male; 50% colorectal; 20% breast; 30% prostate); 45% was ≥ 65 years. Sarcopenia was present in 63.9% and low muscle attenuation in 69.1% of patients. Results are presented in the table. Patient characteristics (sex, BMI and tumor type) were not different in the 2 groups. There was no significant difference in the prevalence of sarcopenia between the 2 groups. Compared to younger patients low muscle attenuation and the combination of sarcopenia and low muscle attenuation were more prevalent in older patients.
Age (y) mean (sd) Sex (male), n (%) Tumor type CRC Breast Prostate BMI (kg/m2) mean (sd) Sarcopenia, n (%) † Low muscle attenuation, n (%) ‡ Sarcopenia + low muscle Attenuation, n (%)
All patientsN = 97
Patients b 65 yrsN = 53
63.8 (9.9) 57 (59)
56.8 (6.8) 31 (59)
49 (50) 19 (20) 29 (30) 25.5 (3.8) 62 (64) 67 (70) 47 (49)
24 (45) 13 (25) 16 (30) 25.9 (4.1) 30.0 (56.6) 32 (60) 20 (38)
Patients ≥ 65 yrsN = 44 Age (y) mean (sd) Sex (male), n (%) Tumor type CRC Breast Prostate BMI (kg/m2) mean (sd) Sarcopenia, n (%) † Low muscle attenuation, n (%) ‡ Sarcopenia + low muscle Attenuation, n (%)
72.2 (5.5) 26 (59) 25 (57) 6 (13) 13 (30) 24.9 (3.4) 32 (73) 35 (80) 27 (61)
p-value ^ NS NS
NS NS b0.05 b0.05
^ P-value calculated using Students t-tests or Chi-square tests.
Disclosure of Interest: None Declared
†Sarcopenia defined as skeletal muscle index b 43 cm2/m2 (men, BMI b 25); b53 cm2/m2 (men, BMI ≥ 25); b 41 cm2/m2 (women).
Keyword: Lymphoma
‡Low muscle attenuation defined as muscle attenuation b 41 HU (BMI b 25); b33 HU (BMI ≥ 25).
doi:10.1016/j.jgo.2013.09.087
Track 3 - New therapies and Basic Science Basic research P084 Sarcopenia is prevalent in more than half of older and younger patients with cancer K.S. Versteeg1,*, S. Blauwhoff-Buskermolen2, M.A. van Bokhorst- de van der Schueren2, J.A. Langius2, A.B. Maier3, I.R. Konings1, H.M.
Conclusion: Sarcopenia and low muscle attenuation are prevalent in more than half of patients with advanced cancer. Low muscle attenuation is more prevalent in older patients than in younger patients. Whether low muscle attenuation and possibly sarcopenia are associated with an increased toxicity rate and worse overall survival is currently under investigation. Disclosure of Interest: None Declared
S62
2013 SIOG Poster Abstracts
Keywords: Basic research Reference
Disclosure of Interest: None Declared
1. Martin et al., 2013 Martin, et al. J Clin Oncol 2013:1539–1547.
Keywords: Basic research
doi:10.1016/j.jgo.2013.09.088
doi:10.1016/j.jgo.2013.09.089
Track 3 - New therapies and Basic Science Basic research P085 Characterization of cisplatin-loaded cubosomes and hexosomes: Effect of mixing with human plasma I.D. Mat Azmi1,*, C. Nilsson1, S. Stürup1, J. Østergaard1, B. Gammelgaard1, S.M. Moghimi2, A. Urtti3. 1Pharmacy, University of Copenhagen, DK-2100 Copenhagen; 2Centre for Pharmaceutical Nanotechnology and Nanotoxicology, Copenhagen, Denmark; 3Centre for Drug Research, University of Helsinki, Helsinki, Finland
Track 3 - New therapies and Basic Science Basic research P086 Role of aging in the modulation of early events of carcinogenesis after exposure in vitro to urban pollution particulate matter B. Fougère1,2,3,*, S. Billet1,2, C. Lepers1,2, P.J. Martin1,2, L. Armand1,2, H. Bulckaen3, F. Roy Saint-Georges4, A. Verdin1,2, P. Gosset1,2,5, P. Shirali1,2. 1 Nord, Université Lille Nord de France, Lille; 2Nord, Unité de Chimie Environnementale et Interactions sur le Vivant (EA4492), Université du Littoral Côte d’Opale, Dunkerque; 3Nord, Service de Gériatrie, Groupement des Hôpitaux de l’Institut Catholique de Lille; 4Nord, Service de Pneumologie, Groupement des Hôpitaux de l’Institut Catholique de Lille; 5 Nord, Service d’Anatomie Pathologique, Groupement des Hôpitaux de l’Institut Catholique de Lille, Lille, France
Introduction: Cubosomes and hexosomes enveloping well-defined nanostructures could be promising candidates for the formation of safe and efficient nanocarriers of anticancer drugs intended for the intravenous administration (IV). Objectives: In this context, the present work addresses different basic challenges such as the effects of cisplatin and salt concentration on the internal nanostructures of injectable cubosomes and hexosomes and also their stability after incubating in human plasma. Methods: The experiments were designed to mimic the physiological conditions within 17 hours in order to fully understand the dynamic behavior and the phase transition of these self-assembled nanocarriers upon exposure to the biological environment. The structural events occurring after the direct contact of the cubosomes and hexosomes with human plasma at different time intervals were investigated using small angle X-ray (SAXS) method. In particular, the effect of different lipid compositions on the internal nanostructures of cisplatin-free and cisplatin-loaded cubosomes and hexosomes was evaluated. The investigated dispersions were either neutral or negatively charged. They based therefore on phytantriol (PHYT), or binary mixtures of PHYT/vitamin E or PHYT/1,2-distearoyl-sn-glycero-3-phosphoglycerol (DSPG). Results: The obtained SAXS patterns show a strong interaction of the neutral PHYT-based cubosomal formulation with human plasma. It triggered the structural transition of the internal biphasic nanostructure (a bicontinuous cubic phase of the symmetry Pn3m co-existing with inverted type hexagonal (H2) phase) to completely neat H2 phase (hexosomes) after 17 hr of incubation in human plasma. In addition, our results revealed an interesting different behavior of hexosomes based on the neutral lipids (8 wt % of PHYT of total dispersion concentration), than that based on the binary PHYT/DSPG mixture with a weight ratio of 90/10 and a total concentration of 8 wt%. The cisplatin-free and cisplatin-loaded hexosomal formulations based on neutral lipids were stable. There is is no indication on the interaction of these dispersions with plasma components that could affect the internal nanostructure. However, the internal H2 nanostructure of hexosomes in the presence of the negatively charged lipid DSPG was affected upon direct contact with human plasma. An additional peak was observed at lower q value in the obtained SAXS patterns after 10 min of incubation. It indicates most likely the formation of traces of new swollen H2 phase coexisting with the initial H2 phase. Conclusion: The obtained results show that the effect of human plasma on the internal nanostructures of these lipidic nanostructured aqueous dispersions is strongly affected by the lipid composition. The presence of the negatively charged lipid DSPG is most likely shows a binding effect to plasma components, thus induces a slightly change on the internal nanostructure of hexosomes upon direct contact with human plasma.
Introduction: The fine air pollution Particulate Matter (PM2.5) is of public health concern. However, even if everybody can suffer from the consequences of chronic exposure to atmospheric pollution, some populations are more fragile. Among them, the elderly are suspected to have a greater sensitivity to chemicals than global population. The elderly are more subject to carcinogenesis and the air pollution particulate matter could be aggravated this phenomenon. The mechanisms usually described in PM2.5 toxicity (i.e. oxidative stress, disproportionate inflammatory response) can not explain all of the early events involved in carcinogenesis. Some genotoxic and epigenetic events are implied in both cellular aging and carcinogenesis such as telomere shortening or aberrant methylation of genes promoters (ex: P16INK4A, MGMT). Objectives: To enhance the knowledge about the influence of age in biological response, blood lymphocytes were sampled from three age classes: 25-30, 50-55, and 75-80 years old after validation of the protocol by the ethical committee. Early markers participating in multistep process of carcinogenesis were then analyzed following in vitro exposure to PM2.5. Methods: 90 blood samples were collected (30/age class). The lymphocytes were isolated by Ficoll, stimulated by phytohemaglutinine, and exposed to urban PM2.5 during two cycles of division. The methylation of P16INK4A and MGMT genes promoters and the telomerase activity were analyzed by qPCR. Results: The oncogenic markers measured appear to be modulated in lymphocytes exposed to PM2.5. Even if, the increase in telomerase activity is constant between the three age classes, the methylation of P16INK4A gene promoter is induced in the 75-80 years old group. The methylation of MGMT gene promoter is itself significantly reduced in the elderly. Conclusion: The 75-80 years old group is the one that is most pronounced markers of tumorigenicity after exposure to air pollution particulate matter. The lower efficiency of repair mechanisms in the elderly could explain their greater susceptibility to cancers described in epidemiological studies. Disclosure of Interest: None Declared
Keywords: Basic research, Lung doi:10.1016/j.jgo.2013.09.090
Track 2 - Haem malignancies in the elderly Lymphoma in the elderly P083 Non-anthracycline and dose-attenuated immunochemotherapy regimen (R-daCVP) in frail and highly elderly patients older than 70 years with later stage of diffuse large B-cell lymphoma J.H. Lim1,*, C.S. Kim2, Y.H. Park1, H.G. Yi1, J.C. Kim1, M.H. Lee1. 1 Internal Medicine; 2Inha University School of Medicine, INCHEON, Korea, Republic Of Introduction: Combination chemotherapy of R-CHOP is the standard treatment for patients with diffuse large B-cell lymphoma (DLBL) even in elderly patients. Patients with DLBL who are elderly and have poor performance status (≥ ECOG PS 2) are difficult to treat with a full course of R-CHOP therapy. Objectives: We have tried to treat these advanced and poor performance status of elderly DLBL patients with rituximab and dose attenuated chemotherapy without anthracycline. (R-daCVP) We retrospectively evaluated the efficacy and safety of the R-daCVP chemotherapy in these patients. Methods: From January 1, 2005 to December 31, 2011, newly diagnosed stage III-IV DLBL patients who were considered inappropriate to receive standard R-CHOP chemotherapy were enrolled in this study. The inclusion criteria of our study were as follows; diagnosis of DLBL that was confirmed by histological examination in patients aged ≥70 years and poor performance status (PS) (ECOG PS ≥2). Patients received rituximab 375 mg/m2 on day 1 of each cycle. Dose attenuated CVP consisted of cyclophosphamide 600 mg/m2 and vincristine 1 mg/ m2 (maximum 2 mg) that were given intravenously on day 1 and oral prednisolone 80 mg on days 1–5. The treatment was repeated every 3 weeks and it was continued for six or eight cycles, with withdrawal due to toxicity or disease progression. Chemotherapy dose modification was done by assessment of toxicities according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0. Results: We finally analyzed 13 patients. The median age was 78 years (range, 71-82). The distribution of the ECOG performance status was as follows: five patients (38.5%) with a performance status of 2, 8 patients (61.5%) with a performance status of 3. Eight patients (61.5%) were stage IV. Only 3 patients showed complete responses. Severe and fatal toxicity was significantly higher among these patients treated with even this less aggressive therapy. Four patients died due to grade 4 hematologic toxicities (grade 4 thrombocytopenia and grade 4 febrile neutropenia). Conclusion: In our study, we could not demonstrate that nonanthracycline dose attenuated combination immunochemotherapy with rituximab may have good potential in elderly DLBL patients with a poor PS. Eldely patients tend to have lower haemoglobin, leukocyte and platelet levels and may suffer greater toxicity from myelosuppressive chemotherapy. Careful toxicity monitoring and controlling the dose intensity or density may be needed in these fragile patients. Further studies are clearly warranted to identify the optimal management strategies for fragile and elderly patients with advanced DLBL.
S61
Verheul1. 1Medical Oncology; 2Nutrition and Dietetics; 3Geriatrics and Gerontology, VU University Medical Center, Amsterdam, Netherlands Introduction: In patients with cancer, sarcopenia (low skeletal muscle mass) and low muscle attenuation (increased proportion of inter- and intramuscular fat) are associated with increased toxicity. The prevalence of sarcopenia increases with age in the healthy population, but it is unclear whether sarcopenia is more prevalent in older compared to younger patients with cancer. Objectives: To study the prevalence of sarcopenia and low muscle attenuation in patients ≥65 years compared to patients b65 years with advanced cancer. Methods: In patients with advanced cancer (colorectal, breast- or prostate) weight, height and BMI were assessed before start of standard chemotherapy. Skeletal muscle mass and muscle attenuation were measured at the third lumbar vertebra with SliceOmatic software (v5.0) on CT images. Sarcopenia and low muscle attenuation were defined according to the sex- and BMI specific threshold values associated with low survival by Martin et al. Patients were divided into 2 age-groups (b65 and ≥65) to assess whether differences in the prevalence of sarcopenia and low muscle attenuation are present. Results: Data were obtained from 97 patients (59% male; 50% colorectal; 20% breast; 30% prostate); 45% was ≥ 65 years. Sarcopenia was present in 63.9% and low muscle attenuation in 69.1% of patients. Results are presented in the table. Patient characteristics (sex, BMI and tumor type) were not different in the 2 groups. There was no significant difference in the prevalence of sarcopenia between the 2 groups. Compared to younger patients low muscle attenuation and the combination of sarcopenia and low muscle attenuation were more prevalent in older patients.
Age (y) mean (sd) Sex (male), n (%) Tumor type CRC Breast Prostate BMI (kg/m2) mean (sd) Sarcopenia, n (%) † Low muscle attenuation, n (%) ‡ Sarcopenia + low muscle Attenuation, n (%)
All patientsN = 97
Patients b 65 yrsN = 53
63.8 (9.9) 57 (59)
56.8 (6.8) 31 (59)
49 (50) 19 (20) 29 (30) 25.5 (3.8) 62 (64) 67 (70) 47 (49)
24 (45) 13 (25) 16 (30) 25.9 (4.1) 30.0 (56.6) 32 (60) 20 (38)
Patients ≥ 65 yrsN = 44 Age (y) mean (sd) Sex (male), n (%) Tumor type CRC Breast Prostate BMI (kg/m2) mean (sd) Sarcopenia, n (%) † Low muscle attenuation, n (%) ‡ Sarcopenia + low muscle Attenuation, n (%)
72.2 (5.5) 26 (59) 25 (57) 6 (13) 13 (30) 24.9 (3.4) 32 (73) 35 (80) 27 (61)
p-value ^ NS NS
NS NS b0.05 b0.05
^ P-value calculated using Students t-tests or Chi-square tests.
Disclosure of Interest: None Declared
†Sarcopenia defined as skeletal muscle index b 43 cm2/m2 (men, BMI b 25); b53 cm2/m2 (men, BMI ≥ 25); b 41 cm2/m2 (women).
Keyword: Lymphoma
‡Low muscle attenuation defined as muscle attenuation b 41 HU (BMI b 25); b33 HU (BMI ≥ 25).
doi:10.1016/j.jgo.2013.09.087
Track 3 - New therapies and Basic Science Basic research P084 Sarcopenia is prevalent in more than half of older and younger patients with cancer K.S. Versteeg1,*, S. Blauwhoff-Buskermolen2, M.A. van Bokhorst- de van der Schueren2, J.A. Langius2, A.B. Maier3, I.R. Konings1, H.M.
Conclusion: Sarcopenia and low muscle attenuation are prevalent in more than half of patients with advanced cancer. Low muscle attenuation is more prevalent in older patients than in younger patients. Whether low muscle attenuation and possibly sarcopenia are associated with an increased toxicity rate and worse overall survival is currently under investigation. Disclosure of Interest: None Declared
S62
2013 SIOG Poster Abstracts
Keywords: Basic research Reference
Disclosure of Interest: None Declared
1. Martin et al., 2013 Martin, et al. J Clin Oncol 2013:1539–1547.
Keywords: Basic research
doi:10.1016/j.jgo.2013.09.088
doi:10.1016/j.jgo.2013.09.089
Track 3 - New therapies and Basic Science Basic research P085 Characterization of cisplatin-loaded cubosomes and hexosomes: Effect of mixing with human plasma I.D. Mat Azmi1,*, C. Nilsson1, S. Stürup1, J. Østergaard1, B. Gammelgaard1, S.M. Moghimi2, A. Urtti3. 1Pharmacy, University of Copenhagen, DK-2100 Copenhagen; 2Centre for Pharmaceutical Nanotechnology and Nanotoxicology, Copenhagen, Denmark; 3Centre for Drug Research, University of Helsinki, Helsinki, Finland
Track 3 - New therapies and Basic Science Basic research P086 Role of aging in the modulation of early events of carcinogenesis after exposure in vitro to urban pollution particulate matter B. Fougère1,2,3,*, S. Billet1,2, C. Lepers1,2, P.J. Martin1,2, L. Armand1,2, H. Bulckaen3, F. Roy Saint-Georges4, A. Verdin1,2, P. Gosset1,2,5, P. Shirali1,2. 1 Nord, Université Lille Nord de France, Lille; 2Nord, Unité de Chimie Environnementale et Interactions sur le Vivant (EA4492), Université du Littoral Côte d’Opale, Dunkerque; 3Nord, Service de Gériatrie, Groupement des Hôpitaux de l’Institut Catholique de Lille; 4Nord, Service de Pneumologie, Groupement des Hôpitaux de l’Institut Catholique de Lille; 5 Nord, Service d’Anatomie Pathologique, Groupement des Hôpitaux de l’Institut Catholique de Lille, Lille, France
Introduction: Cubosomes and hexosomes enveloping well-defined nanostructures could be promising candidates for the formation of safe and efficient nanocarriers of anticancer drugs intended for the intravenous administration (IV). Objectives: In this context, the present work addresses different basic challenges such as the effects of cisplatin and salt concentration on the internal nanostructures of injectable cubosomes and hexosomes and also their stability after incubating in human plasma. Methods: The experiments were designed to mimic the physiological conditions within 17 hours in order to fully understand the dynamic behavior and the phase transition of these self-assembled nanocarriers upon exposure to the biological environment. The structural events occurring after the direct contact of the cubosomes and hexosomes with human plasma at different time intervals were investigated using small angle X-ray (SAXS) method. In particular, the effect of different lipid compositions on the internal nanostructures of cisplatin-free and cisplatin-loaded cubosomes and hexosomes was evaluated. The investigated dispersions were either neutral or negatively charged. They based therefore on phytantriol (PHYT), or binary mixtures of PHYT/vitamin E or PHYT/1,2-distearoyl-sn-glycero-3-phosphoglycerol (DSPG). Results: The obtained SAXS patterns show a strong interaction of the neutral PHYT-based cubosomal formulation with human plasma. It triggered the structural transition of the internal biphasic nanostructure (a bicontinuous cubic phase of the symmetry Pn3m co-existing with inverted type hexagonal (H2) phase) to completely neat H2 phase (hexosomes) after 17 hr of incubation in human plasma. In addition, our results revealed an interesting different behavior of hexosomes based on the neutral lipids (8 wt % of PHYT of total dispersion concentration), than that based on the binary PHYT/DSPG mixture with a weight ratio of 90/10 and a total concentration of 8 wt%. The cisplatin-free and cisplatin-loaded hexosomal formulations based on neutral lipids were stable. There is is no indication on the interaction of these dispersions with plasma components that could affect the internal nanostructure. However, the internal H2 nanostructure of hexosomes in the presence of the negatively charged lipid DSPG was affected upon direct contact with human plasma. An additional peak was observed at lower q value in the obtained SAXS patterns after 10 min of incubation. It indicates most likely the formation of traces of new swollen H2 phase coexisting with the initial H2 phase. Conclusion: The obtained results show that the effect of human plasma on the internal nanostructures of these lipidic nanostructured aqueous dispersions is strongly affected by the lipid composition. The presence of the negatively charged lipid DSPG is most likely shows a binding effect to plasma components, thus induces a slightly change on the internal nanostructure of hexosomes upon direct contact with human plasma.
Introduction: The fine air pollution Particulate Matter (PM2.5) is of public health concern. However, even if everybody can suffer from the consequences of chronic exposure to atmospheric pollution, some populations are more fragile. Among them, the elderly are suspected to have a greater sensitivity to chemicals than global population. The elderly are more subject to carcinogenesis and the air pollution particulate matter could be aggravated this phenomenon. The mechanisms usually described in PM2.5 toxicity (i.e. oxidative stress, disproportionate inflammatory response) can not explain all of the early events involved in carcinogenesis. Some genotoxic and epigenetic events are implied in both cellular aging and carcinogenesis such as telomere shortening or aberrant methylation of genes promoters (ex: P16INK4A, MGMT). Objectives: To enhance the knowledge about the influence of age in biological response, blood lymphocytes were sampled from three age classes: 25-30, 50-55, and 75-80 years old after validation of the protocol by the ethical committee. Early markers participating in multistep process of carcinogenesis were then analyzed following in vitro exposure to PM2.5. Methods: 90 blood samples were collected (30/age class). The lymphocytes were isolated by Ficoll, stimulated by phytohemaglutinine, and exposed to urban PM2.5 during two cycles of division. The methylation of P16INK4A and MGMT genes promoters and the telomerase activity were analyzed by qPCR. Results: The oncogenic markers measured appear to be modulated in lymphocytes exposed to PM2.5. Even if, the increase in telomerase activity is constant between the three age classes, the methylation of P16INK4A gene promoter is induced in the 75-80 years old group. The methylation of MGMT gene promoter is itself significantly reduced in the elderly. Conclusion: The 75-80 years old group is the one that is most pronounced markers of tumorigenicity after exposure to air pollution particulate matter. The lower efficiency of repair mechanisms in the elderly could explain their greater susceptibility to cancers described in epidemiological studies. Disclosure of Interest: None Declared
Keywords: Basic research, Lung doi:10.1016/j.jgo.2013.09.090