factors hormonals i limfomes - · pdf filelimfoma, dins l’estudi epilymph europa....
TRANSCRIPT
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Grup d’Investigació de la Epidemiologia dels Limfomes
Factors Hormonals i Limfomes
Dra. Laura Costas CaudetUnitat d’Infeccions i Càncer - Institut Català d’Oncologia
Barcelona, 13 de Gener 2012
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Índex
- Introducció
- Estudi factors hormonals a l’ Epilymph – Europa
- Noves línies de recerca
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Índex
- Introducció
- Estudi factors hormonals a l’ Epilymph – Europa
- Noves línies de recerca
![Page 4: Factors Hormonals i Limfomes - · PDF filelimfoma, dins l’estudi Epilymph Europa. Objectiu Costas L, et al. Cancer Causes Control. 2012 Jan;23(1):195-206. 2302 casos incidents (1027](https://reader038.vdocuments.mx/reader038/viewer/2022103106/5a74a35d7f8b9a1b688bcb31/html5/thumbnails/4.jpg)
Incidence of Non Hodgkin’s lymphomas
Annual increase4% in Europe3% in USA
SEER 1973‐99
Vam començar perquè...
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Annual increase4% in Europe3% in USA
SEER 1973‐99
Vam començar perquè...
Cambios en la incidencia de linfomas en la población de
Tarragona 1984-1992
Sanjosé, S; Galcerán, J; Álvaro, T; Bosch, R; Borràs, J; Gumà, J;
Martínez, S; Bosch, F XGac Sanit. 1998;12:283-5. - vol.12
núm 6
INCREMENTO ANUAL 3.5%
Incidence of Non Hodgkin’s lymphomas
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MULTICENTRIC CASE-CONTROL STUDY: EPILYMPH
Coordinated by:IARC & Catalan Institute of Oncology
ISRAEL
Hospital Ramon y Cajal, MadridHospital Verge de la Cinta,TortosaHospital U. Sant Joan de ReusHospital Bellvitge, BarcelonaInstitut Catala d’Oncologia
1998
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InterLymph
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Introducció
El nostre grup estudia els factors de risc dels limfomes.
Incidence rates for Spanish cancer registries
CI5C-IX (1997-2001).Factors genètics / virals / ambientals
Què causa els limfomes?
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Lymphomasin a susceptible host
Infectious agents Immune system Environmental
Virus: EBV, HHV-8, HTLV, HCV, HIV,Bacteria: H pylori, Borrelia b.
Poliomavirus
Human Immunodeficiency virusOrgan transplant
Autoimmune diseases
Congenital immune deficiencies
PesticidesOrganochlorines
BenzeneRadiation
Genetic
Introducció
Què causa els limfomes?
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1998‐99 2000‐02 2003‐05 2006‐08 2009‐11
Personal Investigador Publicacions
Publicacions
Publicacions (>60)
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• Clin Gastroenterol Hepatol. 2008 Apr;6(4):451-8.• Hepatitis C and non-Hodgkin lymphoma among
4784 cases and 6269 controls from the International Lymphoma Epidemiology Consortium.
• de Sanjose S, Benavente Y, Vajdic CM, Engels EA, Morton LM, Bracci PM, Spinelli JJ, Zheng T, Zhang Y, Franceschi S, Talamini R, Holly EA, Grulich AE, Cerhan JR, Hartge P, Cozen W, Boffetta P, Brennan P, Maynadié M, Cocco P, Bosch R, Foretova L, Staines A, Becker N, Nieters A.
“Most loved” ...
These results confirm the association between HCV infection and NHL and specific B-NHL subtypes:- diffuse large B-cell lymphoma, - marginal zone lymphoma, and - lymphoplasmacytic lymphoma.
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Conde et al Nature genetics 2010
To identify susceptibility loci for non-Hodgkin lymphoma subtypes, we conducted a three-stage genome-wide association study.
We identified two variants associated with follicular lymphoma at 6p21.32 (rs10484561, combined P = 1.12 x 10(-29) and rs7755224, combined P = 2.00 x 10(-19); r(2) = 1.0),
Supporting the idea that major histocompatibility complex genetic variation influences follicular lymphoma susceptibility.
“Most loved” ...
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Most cited paper >120Lancet oncology
“Most cited” ...
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“Most recent” ...
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Índex
- Introducció
- Estudi factors hormonals a l’ Epilymph –Europa
- Noves línies de recerca
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Perquè les hormones?
Les taxes d’incidència són més altes en homes que en dones, per a la majoria de subtipus:
Sex Rate Ratios
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Perquè les hormones?
El sistema endocrí i immune estan molt relacionats:
IL-1, IL-2, IL-4, IL-6, IL-10 y TNFα
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Avaluar el rol dels factors hormonals endògens (reproductius) i exògens (anticonceptius) en el risc de limfoma, dins l’estudi Epilymph Europa.
Objectiu
Costas L, et al. Cancer Causes Control. 2012 Jan;23(1):195-206.
2302 casos incidents(1027 dones)
2417 controls(1141 dones)
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Factores Reproductivosy Hormonales
Factores Endógenos
(Reproductivos)
Factores Exógenos
(Anticonceptivos Horm)
Embarazo
Número Hijos
Edad al primer hijoEdad al último hijo
Uso / No uso
Año de calendario
Duración (años)
Edad al primer usoTiempo desde el último
uso
Variables d’ exposició
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Paritat (nº de fills) Factors Reproductius
B - NHL
N OR (CI 95%) N OR (CI 95%)
Por cada hijo (en multíparas), reducción del riesgo de:
13% (95% CI 7% - 19%) *Leucemia L. Crónica*Difuso
Por cada hijo (en multíparas), reducción del riesgo de:
29% (95% CI 6% - 46%)
T-cellB- Cell
Controles
Aquestes dades recolzen la hipòtesi de la paritat com a factor protectorde les neoplàsies limfoides.
Primer estudi a observar-ho en NHL- T.
T - NHL
1 fill 2 fills 3 fills>= 4 fills
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Durada / Any de consum Anticonceptius
Controles B-NHL
N OR (CI 95%)
SUBTIPOS
Leucemia L.Crónica (<1970)DifusoFolicular
SUBTIPOS
SUBTIPOSDifusoFolicular
DifusoFolicular
PERÒ un major risc en les que utilitzen anticonceptius hormonals:
• per un periòde curt (<5 anys) / • abans del 1980 / • +10 anys abans del diagnòstic
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Temps des de l’últim consum Anticonceptivos
Exemple Càncer Mama:
Current 1-9 10-19 >=20
B-NHL:
Temps des de l’últim consum
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Índex
- Introducció
- Estudi factors hormonals a l’ Epilymph – Europa
- Noves línies de recerca
![Page 24: Factors Hormonals i Limfomes - · PDF filelimfoma, dins l’estudi Epilymph Europa. Objectiu Costas L, et al. Cancer Causes Control. 2012 Jan;23(1):195-206. 2302 casos incidents (1027](https://reader038.vdocuments.mx/reader038/viewer/2022103106/5a74a35d7f8b9a1b688bcb31/html5/thumbnails/24.jpg)
Noves línies de recerca /MCC-Spain
L’Estudi MCC-Spain: nou estudi multicas-control poblacional que avalua la influència de factors ambientals i genètics en cinc tipus de tumors comuns al nostre país, incloent-hi la LLC.
En col.laboració amb el ICGC / CLL Genome Project (Elias Campo).
Incorporació recent ICO-Girona.
Paper dels hematòlegs de l’Institut Català d’Oncologia en el reclutament de la LLC.
Objectiu: 500 casos de LLC i un o més controls aparellats per sexe, edat i àrea.
22 hospitals a 10 Comunitats Autònomes
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1- Avaluar factors de risc hormonals, familiars i ambientals associats a LLC (entrevista personal).
2- Avaluar rol d’ infeccions virals comunes (Epstein Barr, Citomegalovirus i Poliomavirus) i LLC.
3- Confirmar rol de polimorfismes recentment associats a LLC en GWAS i la interacció amb exposicions ambientals o infeccioses.
4- Identificar marcadors pronòstics del curs de la LLC
Objectius MCC - LLC
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• Family history of CLL (OR=3.7)
• SNPs in MMP-9/TP73
• Exposure to meat and chicken products (OR= 1.6)
• Aberrant replication of EBV (OR= 3.0)
• Infectious mononucleosis (OR= 1.68)
• Hair dye use before 1980 (OR=2.3)
• Solvents (benzene, toluene and xylene OR=1.4)
• Hormonal Factors (Parity OR=0.79)
Domingo et al. 2005; Casabonne et al. 2010; Moore T et al. 2007; de Sanjose et al. 2009; Becker et al. 2009; Benavente et al 2005; Cocco 2010; Costas et al. 2012
Alguns Factors de Risc identificats per a la CLL
a l’EPILYMPH i Consorci INTERLYMPH
FAMILIARS /GENÈTICS
ZOONOSIS / VIRALS
EXPOSICIONS AMBIENTALS
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Noves línies de recerca /MCC-Spain
Avaluarem (respecte a hormones):
Rol factors hormonals endògens i exògens
Irrupció circadiana
Exposicions ambientals (disruptors hormonals = solvents / pesticides, etc)
Polimorfismes en vies de l’esteroidogènesi
Interaccions gen x ambient
QUESTIONNAIRE
GENERALGENERAL
DemographicsAnthropometrics historySmokingOccupationPhysical activityWater consumption and use Sleeping and sun exposure habitsUse of cosmetics and personal care productsMedical history and use of drugs Reproductive history (women)Family history of diseases
NUTRITIONNUTRITION
PSYCHOLOGY PSYCHOLOGY
CLINICAL DATA
Clinical information
Date of diagnosis
Date of start of treatment
Date of specimen
SPECIMEN
Serum/Plasma
DNA blood
DNA saliva
Hair sample
Nail sample
MEASUREMENT
Waist
Hips
2D:4D ratio
QUESTIONNAIRE
GENERALGENERAL
DemographicsAnthropometrics historySmokingOccupationPhysical activityWater consumption and use Sleeping and sun exposure habitsUse of cosmetics and personal care productsMedical history and use of drugs Reproductive history (women)Family history of diseases
NUTRITIONNUTRITION
PSYCHOLOGY PSYCHOLOGY
QUESTIONNAIRE
GENERALGENERAL
DemographicsAnthropometrics historySmokingOccupationPhysical activityWater consumption and use Sleeping and sun exposure habitsUse of cosmetics and personal care productsMedical history and use of drugs Reproductive history (women)Family history of diseases
NUTRITIONNUTRITION
PSYCHOLOGY PSYCHOLOGY
CLINICAL DATA
Clinical information
Date of diagnosis
Date of start of treatment
Date of specimen
SPECIMEN
Serum/Plasma
DNA blood
DNA saliva
Hair sample
Nail sample
MEASUREMENT
Waist
Hips
2D:4D ratio
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Noves línies de recerca / IMMC
Dins l’IMMC, avaluarem els factors hormonals com a factors de risc de Mieloma Múltiple en estudis de diferents països que col·laboren al Consorci.
Es preveu avaluar un total de 1700 dones amb mieloma i 7000 dones controls.
El Consorci Internacional de Mieloma Múltiple (IMMC) és un grup d'investigadors internacionals que tenen estudis epidemiològics i que duen a terme projectes de recerca col·laborativa compartint i analitzant dades a través de diferents països.
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Gràcies!
Epidemiologia:Laura CostasDelphine Casabonne Yolanda Benavente Clàudia RoblesSilvia de Sanjosé
Suport:Yasmin Sabaté Xesco AlarconMarleny VergaraYolanda Florencia Vanesa Camon
Hematologia :Eva DomingoEva González-BarcaAna OliveiraJose SarràSantiago MercadalVictoria ClapésCristina BacaNadia GarciaConcepció BoquéAlberto Fernandez de Sevilla