Body iron status and gastric cancer risk in the EURGAST study

Ana Fonseca-Nunes, Antonio Agudo, Núria Aranda, Victoria Arija, Amanda J. Cross, Esther Molina, Maria Jose Sanchez, H. B. Bueno-De-Mesquita, Peter Siersema, Elisabete Weiderpass, Vittorio Krogh, Amalia Mattiello, Rosario Tumino, Calogero Saieva, Alessio Naccarati, Bodil Ohlsson, Klas Sjöberg, Marie Christine Boutron-Ruault, Claire Cadeau, Guy FagherazziHeiner Boeing, Annika Steffen, Tilman Kühn, Verena Katzke, Anne Tjønneland, Anja Olsen, Kay Tee Khaw, Nick Wareham, Tim Key, Yunxia Lu, Elio Riboli, Petra H. Peeters, Diana Gavrila, Miren Dorronsoro, José Ramõn Quirõs, Aurelio Barricarte, Mazda Jenab, Raúl Zamora-Ros, Heinz Freisling, Antonia Trichopoulou, Pagona Lagiou, Christina Bamia, Paula Jakszyn

Research output: Contribution to journalArticle

Abstract

Although it appears biologically plausible for iron to be associated with gastric carcinogenesis, the evidence is insufficient to lead to any conclusions. To further investigate the relationship between body iron status and gastric cancer risk, we conducted a nested case-control study in the multicentric European Prospective Investigation into Cancer and Nutrition (EPIC) 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 prediagnostic serum iron, ferritin, transferrin and C-reactive protein, and further estimated total iron-binding capacity (TIBC) and transferrin saturation (TS). Odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of gastric cancer by iron metrics were estimated from multivariable conditional logistic regression models. After adjusting for relevant confounders, we observed a statistically significant inverse association between gastric cancer and ferritin and TS indices (ORlog2=0.80, 95% CI=0.72-0.88; OR10%increment=0.87, 95% CI=0.78-0.97, respectively). These associations appear to be restricted to noncardia gastric cancer (ferritin showed a p for heterogeneity=0.04 and TS had a p for heterogeneity=0.02), and no differences were found by histological type. TIBC increased risk of overall gastric cancer (OR50 μg/dl=1.13, 95% CI=1.02-1.2) and also with noncardia gastric cancer (p for heterogeneity=0.04). Additional analysis suggests that time between blood draw and gastric cancer diagnosis could modify these findings. In conclusion, our results showed a decreased risk of gastric cancer related to higher body iron stores as measured by serum iron and ferritin. Further investigation is needed to clarify the role of iron in gastric carcinogenesis.

Original languageEnglish
Pages (from-to)2904-2914
Number of pages11
JournalInternational Journal of Cancer
Volume137
Issue number12
DOIs
Publication statusPublished - Dec 15 2015

Fingerprint

Stomach Neoplasms
Iron
Transferrin
Ferritins
Confidence Intervals
Stomach
Carcinogenesis
Logistic Models
Serum
C-Reactive Protein
Case-Control Studies
Adenocarcinoma
Odds Ratio
Neoplasms

Keywords

  • gastric cancer
  • iron homeostasis
  • nested case-control study

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Fonseca-Nunes, A., Agudo, A., Aranda, N., Arija, V., Cross, A. J., Molina, E., ... Jakszyn, P. (2015). Body iron status and gastric cancer risk in the EURGAST study. International Journal of Cancer, 137(12), 2904-2914. https://doi.org/10.1002/ijc.29669

Body iron status and gastric cancer risk in the EURGAST study. / Fonseca-Nunes, Ana; Agudo, Antonio; Aranda, Núria; Arija, Victoria; Cross, Amanda J.; Molina, Esther; Sanchez, Maria Jose; Bueno-De-Mesquita, H. B.; Siersema, Peter; Weiderpass, Elisabete; Krogh, Vittorio; Mattiello, Amalia; Tumino, Rosario; Saieva, Calogero; Naccarati, Alessio; Ohlsson, Bodil; Sjöberg, Klas; Boutron-Ruault, Marie Christine; Cadeau, Claire; Fagherazzi, Guy; Boeing, Heiner; Steffen, Annika; Kühn, Tilman; Katzke, Verena; Tjønneland, Anne; Olsen, Anja; Khaw, Kay Tee; Wareham, Nick; Key, Tim; Lu, Yunxia; Riboli, Elio; Peeters, Petra H.; Gavrila, Diana; Dorronsoro, Miren; Quirõs, José Ramõn; Barricarte, Aurelio; Jenab, Mazda; Zamora-Ros, Raúl; Freisling, Heinz; Trichopoulou, Antonia; Lagiou, Pagona; Bamia, Christina; Jakszyn, Paula.

In: International Journal of Cancer, Vol. 137, No. 12, 15.12.2015, p. 2904-2914.

Research output: Contribution to journalArticle

Fonseca-Nunes, A, Agudo, A, Aranda, N, Arija, V, Cross, AJ, Molina, E, Sanchez, MJ, Bueno-De-Mesquita, HB, Siersema, P, Weiderpass, E, Krogh, V, Mattiello, A, Tumino, R, Saieva, C, Naccarati, A, Ohlsson, B, Sjöberg, K, Boutron-Ruault, MC, Cadeau, C, Fagherazzi, G, Boeing, H, Steffen, A, Kühn, T, Katzke, V, Tjønneland, A, Olsen, A, Khaw, KT, Wareham, N, Key, T, Lu, Y, Riboli, E, Peeters, PH, Gavrila, D, Dorronsoro, M, Quirõs, JR, Barricarte, A, Jenab, M, Zamora-Ros, R, Freisling, H, Trichopoulou, A, Lagiou, P, Bamia, C & Jakszyn, P 2015, 'Body iron status and gastric cancer risk in the EURGAST study', International Journal of Cancer, vol. 137, no. 12, pp. 2904-2914. https://doi.org/10.1002/ijc.29669
Fonseca-Nunes A, Agudo A, Aranda N, Arija V, Cross AJ, Molina E et al. Body iron status and gastric cancer risk in the EURGAST study. International Journal of Cancer. 2015 Dec 15;137(12):2904-2914. https://doi.org/10.1002/ijc.29669
Fonseca-Nunes, Ana ; Agudo, Antonio ; Aranda, Núria ; Arija, Victoria ; Cross, Amanda J. ; Molina, Esther ; Sanchez, Maria Jose ; Bueno-De-Mesquita, H. B. ; Siersema, Peter ; Weiderpass, Elisabete ; Krogh, Vittorio ; Mattiello, Amalia ; Tumino, Rosario ; Saieva, Calogero ; Naccarati, Alessio ; Ohlsson, Bodil ; Sjöberg, Klas ; Boutron-Ruault, Marie Christine ; Cadeau, Claire ; Fagherazzi, Guy ; Boeing, Heiner ; Steffen, Annika ; Kühn, Tilman ; Katzke, Verena ; Tjønneland, Anne ; Olsen, Anja ; Khaw, Kay Tee ; Wareham, Nick ; Key, Tim ; Lu, Yunxia ; Riboli, Elio ; Peeters, Petra H. ; Gavrila, Diana ; Dorronsoro, Miren ; Quirõs, José Ramõn ; Barricarte, Aurelio ; Jenab, Mazda ; Zamora-Ros, Raúl ; Freisling, Heinz ; Trichopoulou, Antonia ; Lagiou, Pagona ; Bamia, Christina ; Jakszyn, Paula. / Body iron status and gastric cancer risk in the EURGAST study. In: International Journal of Cancer. 2015 ; Vol. 137, No. 12. pp. 2904-2914.
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AU - Aranda, Núria

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AU - Molina, Esther

AU - Sanchez, Maria Jose

AU - Bueno-De-Mesquita, H. B.

AU - Siersema, Peter

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AU - Krogh, Vittorio

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AU - Olsen, Anja

AU - Khaw, Kay Tee

AU - Wareham, Nick

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AU - Lu, Yunxia

AU - Riboli, Elio

AU - Peeters, Petra H.

AU - Gavrila, Diana

AU - Dorronsoro, Miren

AU - Quirõs, José Ramõn

AU - Barricarte, Aurelio

AU - Jenab, Mazda

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AU - Freisling, Heinz

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AB - Although it appears biologically plausible for iron to be associated with gastric carcinogenesis, the evidence is insufficient to lead to any conclusions. To further investigate the relationship between body iron status and gastric cancer risk, we conducted a nested case-control study in the multicentric European Prospective Investigation into Cancer and Nutrition (EPIC) 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 prediagnostic serum iron, ferritin, transferrin and C-reactive protein, and further estimated total iron-binding capacity (TIBC) and transferrin saturation (TS). Odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of gastric cancer by iron metrics were estimated from multivariable conditional logistic regression models. After adjusting for relevant confounders, we observed a statistically significant inverse association between gastric cancer and ferritin and TS indices (ORlog2=0.80, 95% CI=0.72-0.88; OR10%increment=0.87, 95% CI=0.78-0.97, respectively). These associations appear to be restricted to noncardia gastric cancer (ferritin showed a p for heterogeneity=0.04 and TS had a p for heterogeneity=0.02), and no differences were found by histological type. TIBC increased risk of overall gastric cancer (OR50 μg/dl=1.13, 95% CI=1.02-1.2) and also with noncardia gastric cancer (p for heterogeneity=0.04). Additional analysis suggests that time between blood draw and gastric cancer diagnosis could modify these findings. In conclusion, our results showed a decreased risk of gastric cancer related to higher body iron stores as measured by serum iron and ferritin. Further investigation is needed to clarify the role of iron in gastric carcinogenesis.

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