@article{0c2e21ad9a7c48ca8df437120bcb24c6,
title = "Energy balance-related factors in childhood and adolescence and risk of colorectal cancer expressing different levels of proteins involved in the Warburg-effect",
abstract = "Early-life (childhood to adolescence) energy balance-related factors (height, energy restriction, BMI) have been associated with adult colorectal cancer (CRC) risk. Warburg-effect activation via PI3K/Akt-signaling might explain this link. We investigated whether early-life energy balance-related factors were associated with risk of Warburg-subtypes in CRC. We used immunohistochemistry for six proteins involved in the Warburg-effect (LDHA, GLUT1, MCT4, PKM2, P53, and PTEN) on tissue microarrays of 2399 incident CRC cases from the prospective Netherlands Cohort Study (NLCS). Expression levels of all proteins were combined into a pathway-based sum score and categorized into three Warburg-subtypes (Warburg-low/-moderate/-high). Multivariable Cox-regression analyses were used to estimate associations of height, energy restriction proxies (exposure to Dutch Hunger Winter; Second World War [WWII]; Economic Depression) and adolescent BMI with Warburg-subtypes in CRC. Height was positively associated with colon cancer in men, regardless of Warburg-subtypes, and with Warburg-low colon and Warburg-moderate rectal cancer in women. Energy restriction during the Dutch Hunger Winter was inversely associated with colon cancer in men, regardless of Warburg-subtypes. In women, energy restriction during the Hunger Winter and WWII was inversely associated with Warburg-low colon cancer, whereas energy restriction during the Economic Depression was positively associated with Warburg-high colon cancer. Adolescent BMI was positively associated with Warburg-high colon cancer in men, and Warburg-moderate rectal cancer in women. In conclusion, the Warburg-effect seems to be involved in associations of adolescent BMI with colon cancer in men, and of energy restriction during the Economic Depression with colon cancer in women. Further research is needed to validate these results.",
keywords = "colorectal cancer, early-life energy balance, etiological heterogeneity, prospective cohort study, Warburg-effect, EARLY-LIFE, COHORT, INSULIN, HEIGHT, ASSOCIATIONS, RESTRICTION, OBESITY, FAMINE, EPIDEMIOLOGY, MECHANISMS",
author = "J.C.A. Jenniskens and K. Offermans and C.C.J.M. Simons and I. Samarska and G.E. Fazzi and K.M. Smits and L.J. Schouten and M.P. Weijenberg and H.I. Grabsch and {van den Brandt}, P.A.",
note = "Funding Information: The Rainbow‐TMA consortium was financially supported by BBMRI‐NL, a Research Infrastructure financed by the Dutch government (NWO 184.021.007, to Piet A. van den Brandt), and Maastricht University Medical Center, University Medical Center Utrecht and Radboud University Medical Centre, the Netherlands. The authors would like to thank all investigators from the Rainbow‐TMA consortium project group [Piet A. van den Brandt, A. zur Hausen, Heike I. Grabsch, M. van Engeland, Leo J. Schouten, J. Beckervordersandforth (Maastricht University Medical Center, Maastricht, Netherlands); P. H. M. Peeters, P. J. van Diest, H. B. Bueno de Mesquita (University Medical Center Utrecht, Utrecht, Netherlands); J. van Krieken, I. Nagtegaal, B. Siebers, B. Kiemeney (Radboud University Medical Center, Nijmegen, Netherlands); F. J. van Kemenade, C. Steegers, D. Boomsma, G. A. Meijer (VU University Medical Center, Amsterdam, Netherlands); F. J. van Kemenade, B. Stricker (Erasmus University Medical Center, Rotterdam, Netherlands); L. Overbeek, A. Gijsbers (PALGA, the Nationwide Histopathology and Cytopathology Data Network and Archive, Houten, Netherlands)] and collaborating pathologists [Among others: A. de Bru{\"i}ne (VieCuri Medical Center, Venlo); J. C. Beckervordersandforth (Maastricht University Medical Center, Maastricht); J. van Krieken, I. Nagtegaal (Radboud University Medical Center, Nijmegen); W. Timens (University Medical Center Groningen, Groningen); F. J. van Kemenade (Erasmus University Medical Center, Rotterdam); M. C. H. Hogenes (Laboratory for Pathology OostNederland, Hengelo); P. J. van Diest (University Medical Center Utrecht, Utrecht); R. E. Kibbelaar (Pathology Friesland, Leeuwarden); A. F. Hamel (Stichting Samenwerkende Ziekenhuizen Oost‐Groningen, Winschoten); A. T. M. G. Tiebosch (Martini Hospital, Groningen); C. Meijers (Reinier de Graaf Gasthuis/ S.S.D.Z., Delft); R. Natt{\'e} (Haga Hospital Leyenburg, The Hague); G. A. Meijer (VU University Medical Center, Amsterdam); J. J. T. H. Roelofs (Academic Medical Center, Amsterdam); R. F. Hoedemaeker (Pathology Laboratory Pathan, Rotterdam); S. Sastrowijoto (Orbis Medical Center, Sittard); M. Nap (Atrium Medical Center, Heerlen); H. T. Shirango (Deventer Hospital, Deventer); H. Doornewaard (Gelre Hospital, Apeldoorn); J. E. Boers (Isala Hospital, Zwolle); J. C. van der Linden (Jeroen Bosch Hospital, Den Bosch); G. Burger (Symbiant Pathology Center, Alkmaar); R. W. Rouse (Meander Medical Center, Amersfoort); P. C. de Bruin (St. Antonius Hospital, Nieuwegein); P. Drillenburg (Onze Lieve Vrouwe Gasthuis, Amsterdam); C. van Krimpen (Kennemer Gasthuis, Haarlem); J. F. Graadt van Roggen (Diaconessenhuis, Leiden); S. A. J. Loyson (Bronovo Hospital, The Hague); J. D. Rupa (Laurentius Hospital, Roermond); H. Kliffen (Maasstad Hospital, Rotterdam); H. M. Hazelbag (Medical Center Haaglanden, The Hague); K. Schelfout (Stichting Pathologisch en Cytologisch Laboratorium West‐Brabant, Bergen op Zoom); J. Stavast (Laboratorium Klinische Pathologie Centraal Brabant, Tilburg); I. van Lijnschoten (PAMM laboratory for Pathology and Medical Microbiology, Eindhoven); K. Duthoi (Amphia Hospital, Breda)]. Funding Information: This project was funded by The Dutch Cancer Society (KWF 11044 to Piet A. van den Brandt). Funding Information Publisher Copyright: {\textcopyright} 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.",
year = "2022",
month = jun,
day = "1",
doi = "10.1002/ijc.33941",
language = "English",
volume = "150",
pages = "1812--1824",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "John Wiley & Sons Inc.",
number = "11",
}