GRUP DE RECERCA UNITAT DE NUTRICIÓ, MEDI AMBIENT I CÀNCER – UNAC

Institut Català d’Oncologia – IDIBELL (Barcelona)

Director: Carlos Alberto González
Adreça mail de contacte del grup de Recerca: aexposito@iconcologia.net
Telèfon de contacte: (+34) 932 60 74 01

Actualització fitxa tècnica del grup: juliol 2017

MEMBRES DEL GRUP INVESTIGADOR

Carlos A. González, Director

Antonio Agudo Trigueros, Cap de la Unitat, Institut Català d’Oncologia
a/e: a.agudo@iconcologia.net

Núria Sala Serra, Investigador Sènior, Institut Català d’Oncologia
a/e: nsala@iconcologia.net

Eric J Duell, Investigador Sènior, Institut Català d’Oncologia
a/e: eduell@iconcologia.net

Paula Jakszyn, Investigador Sènior, Institut Català d’Oncologia
a/e: paujak@iconcologia.net

Raúl Zamora Ros, Investigador Sènior, Institut Català d’Oncologia
a/e: rzamora@iconcologia.net

Catalina Bonet Bonet, Estadística, Institut Català d’Oncologia
a/e: cbonet@iconcologia.net

Leila Luján Barroso, Estadística, Institut Català d’Oncologia
a/e: llujan@iconcologia.net

Valerie Cayssials, Estadística, Institut Català d’Oncologia
a/e: vcayssials@iconcologia.net

Nadia García Lozano, Tècnic laboratori, Institut Català d’Oncologia
a/e: nglozano@iconcologia.net

Carlota Castro Espín, Tècnic Assaig Clínics, Institut Català d’Oncologia
a/e: ccespin@iconcologia.net

ACTIVITATS I CAPACITATS DEL GRUP DE RECERCA

La Unitat de Nutrició i Càncer (UNAC) està formada per un grup multidisciplinari que inclou epidemiòlegs, estadístics, especialistes en nutrició, informàtics, biòlegs moleculars i genetistes. El focus principal de la Unitat és la investigació etiològica del càncer en el marc de l’estudi europeu EPIC de Dieta, Càncer i Salut, promogut per la Unió Europea i coordinat per l’Agència Internacional per a la Investigació del Càncer (IARC-OMS) i l’Imperial College de Londres.

La Unitat coordina el projecte EPIC a Espanya. L’estratègia científica de l’estudi EPIC es basa en primer lloc en reconèixer que el càncer és un procés complex que involucra múltiples factors ambientals i genètics. En segon lloc, l’estratègia entén que fer progressos en termes de coneixement científic de la relació causal entre l’exposició dietètica i altres factors ambientals i el càncer requereix un enfocament innovador que inclogui simultàniament la combinació d’instruments tradicionals d’epidemiologia amb l’ús de marcadors bioquímics i biològics d’exposició, així com els marcadors genètics de susceptibilitat. L’estudi de la interacció de factors ambientals amb factors genètics és una part clau de l’etiopatogènia.

La Unitat lidera la recerca en càncer gàstric i adenocarcinoma esofàgic a EPIC Europa. La UNAC també treballa en estreta col·laboració amb altres grups de recerca d’EPIC que estudien càncer de pulmó, càncer de pròstata, càncer de bufeta i càncer de coll uterí. Una altra àrea que ha rebut un nou impuls en els últims anys és la investigació sobre el càncer de pàncrees. La UNAC lidera conjuntament un Consorci Internacional per al Control de Casos de Càncer de Pàncrees (PanC4) i és un representant de PanScan, el Consorci EPIC de Cohort de Càncer de Pàncrees.

Una altra àrea de recerca dins del grup és la supervivència del càncer de mama, que s’està investigant com a part d’un nou estudi titulat PREDICOP, un assaig multicèntric controlat aleatòriament dissenyat per avaluar l’efecte d’una intervenció d’estil de vida que combina control de pes , dieta i activitat física. Risc de recaigudes en pacients amb càncer de mama.

LÍNIES DE RECERCA

Línia: EPIC-Eur-Gast és un projecte sobre el càncer d’estómac i d’esòfag: identificació de factors de risc nutricionals, ambientals i genètics de susceptibilitat a la població europea, l’anàlisi de l’expressió gènica i estudis funcionals per caracteritzar la variant causal.
Investigador principal: Antonio Agudo, Raúl Zamora.

Línia: Identificació dels marcadors en la progressió de les lesions preneoplàsiques de càncer gàstric a Espanya.
Investigador principal: Núria Sala

Línia: L’exposició endògena i exògena a les nitrosamines, la ingesta de ferro total i grups hemo, l’homeòstasi del ferro, la susceptibilitat genètica i risc de càncer en la població adulta a Europa.
Investigador principal: Paula Jakszyn

Línia: Biomarcadors d’exposició a la acrilamida, la susceptibilitat genètica i el risc de càncer d’endometri i d’ovari. La ingesta dietètica d’acrilamida i el risc de càncer de pàncrees i d’esòfag a Europa.
Investigador principal: Eric J Duell

Línia: Reducció de les recurrències del càncer de mama a través del control de pes, la intervenció dietètica i activitat física.
Investigador principal: Antonio Agudo

MILLORS PUBLICACIONS DEL GRUP (2015-2017)

Duell EJ, Lujan-Barroso L, Sala N, Deitz McElyea S, Overvad K, Tjonneland A, Olsen A, Weiderpass E, Busund LT, Moi L, Muller D, Vineis P, Aune D, Matullo G, Naccarati A, Panico S, Tagliabue G, Tumino R, Palli D, Kaaks R, Katzke VA, Boeing H, Bueno-de-Mesquita HBA, Peeters PH, Trichopoulou A, Lagiou P, Kotanidou A, Travis RC, Wareham N, Khaw KT, Ramon Quiros J, Rodríguez-Barranco M, Dorronsoro M, Chirlaque MD, Ardanaz E, Severi G, Boutron-Ruault MC, Rebours V, Brennan P, Gunter M, Scelo G, Cote G, Sherman S, Korc M.
Plasma microRNAs as biomarkers of pancreatic cancer risk in a prospective cohort study.
Int J Cancer. 2017 Sep 1;141(5):905-915. doi: 10.1002/ijc.30790. Epub 2017 Jun 12.
PMID: 28542740

Abstract: Noninvasive biomarkers for early pancreatic ductal adenocarcinoma (PDAC) diagnosis and disease risk stratification are greatly needed. We conducted a nested case-control study within the Prospective Investigation into Cancer and Nutrition (EPIC) cohort to evaluate prediagnostic microRNAs (miRs) as biomarkers of subsequent PDAC risk. A panel of eight miRs (miR-10a, -10b, -21-3p, -21-5p, -30c, -106b, -155 and -212) based on previous evidence from our group was evaluated in 225 microscopically confirmed PDAC cases and 225 controls matched on center, sex, fasting status and age/date/time of blood collection. MiR levels in prediagnostic plasma samples were determined by quantitative RT-PCR. Logistic regression was used to model levels and PDAC risk, adjusting for covariates and to estimate area under the receiver operating characteristic curves (AUC). Plasma miR-10b, -21-5p, -30c and -106b levels were significantly higher in cases diagnosed within 2 years of blood collection compared to matched controls (all p-values <0.04). Based on adjusted logistic regression models, levels for six miRs (miR-10a, -10b, -21-5p, -30c, -155 and -212) overall, and for four miRs (-10a, -10b, -21-5p and -30c) at shorter follow-up time between blood collection and diagnosis (≤5 yr, ≤2 yr), were statistically significantly associated with risk. A score based on the panel showed a linear dose-response trend with risk (p-value = 0.0006). For shorter follow-up (≤5 yr), AUC for the score was 0.73, and for individual miRs ranged from 0.73 (miR-212) to 0.79 (miR-21-5p).

Jakszyn P, Fonseca-Nunes A, Lujan-Barroso L, Aranda N, Tous M, Arija V, Cross A, Bueno-de-Mesquita HBA, Weiderpass E, Kühn T, Kaaks R, Sjöberg K, Ohlsson B, Tumino R, Palli D, Ricceri F, Fasanelli F, Krogh V, Mattiello A, Jenab M, Gunter M, Perez-Cornago A, Khaw KT, Tjønneland A, Olsen A, Overvad K, Trichopoulou A, Peppa E, Vasilopoulou E, Boeing H, Sánchez-Cantalejo E, Huerta JM, Dorronsoro M, Barricarte A, Quirós JM, Peeters PH, Agudo A.
Hepcidin levels and gastric cancer risk in the EPIC-EurGast study.
Int J Cancer. 2017 Sep 1;141(5):945-951.
PMID: 28543377

Abstract; Hepcidin is the main regulator of iron homeostasis and dysregulation of proteins involved in iron metabolism has been associated with tumorogenesis. However, to date, no epidemiological study has researched the association between hepcidin levels and gastric cancer risk. To further investigate the relationship between hepcidin levels and gastric cancer risk, we conducted a nested case-control study (EURGAST) within the multicentric European Prospective Investigation into Cancer and Nutrition study. The study included 456 primary incident gastric adenocarcinoma cases and 900 matched controls that occurred during an average of 11 years of follow-up. We measured serum levels of hepcidin-25, iron, ferritin, transferrin and C-reactive protein. Odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of gastric cancer by hepcidin levels were estimated from multivariable conditional logistic regression models. Mediation effect of the ferritin levels on the hepcidin-gastric cancer pathway was also evaluated. After adjusting for relevant confounders, we observed a statistically significant inverse association between gastric cancer and hepcidin levels (OR 5 ng/l = 0.96, 95% CI = 0.93-0.99). No differences were found by tumor localization or histological type. In mediation analysis, we found that the direct effect of hepcidin only represents a nonsignificant 38% (95% CI: -69%, 91%). In summary, these data suggest that the inverse association of hepcidin levels and gastric cancer risk was mostly accounted by ferritin levels. Further investigation including repeated measures of hepcidin is needed to clarify their role in gastric carcinogenesis.

Agudo A, Peluso M, Munnia A, Luján-Barroso L, Barricarte A, Amiano P, Navarro C, Sánchez MJ, Quirós JR, Ardanaz E, Larrañaga N, Tormo MJ, Chirlaque MD, Rodríguez-Barranco M, Sánchez-Cantalejo E, Cellai F, Bonet C, Sala N, González CA.
Aromatic DNA adducts and breast cancer risk: a case-cohort study within the EPIC-Spain.
Carcinogenesis. 2017 May 23.
PMID: 28535209

Abstract:Epidemiologic evidence linking environmental exposure to polycyclic aromatic hydrocarbons (PAH) with breast cancer is limited. Measurement of DNA adducts formed by aromatic compounds, including PAH, has been carried in breast tissue samples and white blood cells from women with breast cancer and different kinds of controls. However, these studies provide inconsistent results and bias cannot be ruled out. During the 7-year follow-up period, 305 women were diagnosed with first primary breast cancer in the EPIC-Spain cohort, and were compared with a sample of 149 women without breast cancer at recruitment, using a case-cohort approach. Aromatic adducts to DNA from leukocytes collected at recruitment were measured by means of the 32P-postlabelling technique. The relative risk (RR) and 95% confidence interval (CI), adjusted by relevant confounders, were estimated by a modified version of Cox proportional hazards model. There was a significant increased risk for developing breast cancer when DNA adduct concentrations were doubled, with adjusted RR of 1.61 (95% CI 1.29-2.01). The increase in breast cancer risk was observed both for pre- and post-menopausal women. There was a significant interaction with tobacco smoking and body mass index (BMI), with higher effect of DNA adducts on breast cancer risk among smokers and women with normal weight. The results from our study support the hypothesis that factors leading to higher levels of aromatic DNA adducts in white blood cells may be involved in development of breast cancer.

Zamora-Ros R.
Polyphenol epidemiology: looking back and moving forward.
Am J Clin Nutr. 2016 Sep;104(3):549-50.
PMID: 27534644

Duell EJ, Bonet C, Muñoz X, Lujan-Barroso L, Weiderpass E, Boutron-Ruault MC, Racine A, Severi G, Canzian F, Rizzato C, Boeing H, Overvad K, Tjønneland A, Argüelles M, Sánchez-Cantalejo E, Chamosa S, Huerta JM, Barricarte A, Khaw KT, Wareham N, Travis RC, Trichopoulou A, Trichopoulos D, Yiannakouris N, Palli D, Agnoli C, Tumino R, Naccarati A, Panico S, Bueno-de-Mesquita HB, Siersema PD, Peeters PH, Ohlsson B, Lindkvist B, Johansson I, Ye W, Johansson M, Fenger C, Riboli E, Sala N, González CA.
Variation at ABO histo-blood group and FUT loci and diffuse and intestinal gastric cancer risk in a European population.
Int J Cancer. 2015 Feb 15;136(4):880-93.
PMID: 24947433

Abstract: ABO blood serotype A is known to be associated with risk of gastric cancer (GC), but little is known how ABO alleles and the fucosyltransferase (FUT) enzymes and genes which are involved in Lewis antigen formation [and in Helicobacter pylori (H. pylori) binding and pathogenicity] may be related to GC risk in a European population. The authors conducted an investigation of 32 variants at ABO and FUT1-7 loci and GC risk in a case-control study of 365 cases and 1,284 controls nested within the EPIC cohort (the EPIC-Eurgast study). Four variants (including rs505922) in ABO, and allelic blood group A (AO+AA, odds ratio=1.84, 95%CI=1.20-2.80) were associated with diffuse-type GC; however, conditional models with other ABO variants indicated that the associations were largely due to allelic blood group A. One variant in FUT5 was also associated with diffuse-type GC, and four variants (and haplotypes) in FUT2 (Se), FUT3 (Le) and FUT6 with intestinal-type GC. Further, one variant in ABO, two in FUT3 and two in FUT6 were associated with H. pylori infection status in controls, and two of these (in FUT3 and FUT6) were weakly associated with intestinal-type GC risk. None of the individual variants surpassed a Bonferroni corrected p-value cutoff of 0.0016; however, after a gene-based permutation test, two loci [FUT3(Le)/FUT5/FUT6 and FUT2(Se)] were significantly associated with diffuse- and intestinal-type GC, respectively. Replication and functional studies are therefore recommended to clarify the role of ABO and FUT alleles in H. pylori infection and subtype-specific gastric carcinogenesis.

INSTITUCIONS QUE RECONEIXEN AL GRUP DE RECERCA

Grup de recerca oficial de l’IDIBELL (Institut d’Investigació Biomèdica de Bellvitge).
Grup de recerca reconegut per l’AGAUR 2014SGR726.
Membre de la Red Temática de Investigación Cooperativa en Cáncer (RTICC).