title: A Systematic Literature Review and Meta-Regression Analysis on Early-Life Energy Restriction and Cancer Risk in Humans.
abstract: BACKGROUND
  In animal models, long-term moderate energy restriction (ER) is reported to decelerate carcinogenesis, whereas the effect of severe ER is inconsistent. The impact of early-life ER on cancer risk has never been reviewed systematically and quantitatively based on observational studies in humans.
  
  
  OBJECTIVE
  We conducted a systematic review of observational studies and a meta-(regression) analysis on cohort studies to clarify the association between early-life ER and organ site-specific cancer risk.
  
  
  METHODS
  PubMed and EMBASE (1982 -August 2015) were searched for observational studies. Summary relative risks (RRs) were estimated using a random effects model when available ≥3 studies.
  
  
  RESULTS
  Twenty-four studies were included. Eleven publications, emanating from seven prospective cohort studies and some reporting on multiple cancer endpoints, met the inclusion criteria for quantitative analysis. Women exposed to early-life ER (ranging from 220-1660 kcal/day) had a higher breast cancer risk than those not exposed (RRRE all ages = 1.28, 95% CI: 1.05-1.56; RRRE for 10-20 years of age = 1.21, 95% CI: 1.09-1.34). Men exposed to early-life ER (ranging from 220-800kcal/day) had a higher prostate cancer risk than those not exposed (RRRE = 1.16, 95% CI: 1.03-1.30). Summary relative risks were not computed for colorectal cancer, because of heterogeneity, and for stomach-, pancreas-, ovarian-, and respiratory cancer because there were <3 available studies. Longer duration of exposure to ER, after adjustment for severity, was positively associated with overall cancer risk in women (p = 0.02). Ecological studies suggest that less severe ER is generally associated with a reduced risk of cancer.
  
  
  CONCLUSIONS
  Early-life transient severe ER seems to be associated with increased cancer risk in the breast (particularly ER exposure at adolescent age) and prostate. The duration, rather than severity of exposure to ER, seems to positively influence relative risk estimates. This result should be interpreted with caution due to the limited number of studies and difficulty in disentangling duration, severity, and geographical setting of exposure.
authors.affiliation: Department of Epidemiology, GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, the Netherlands.
authors.forename: Rachel J J
authors.initials: RJ
authors.lastname: Elands
authors.affiliation: Department of Epidemiology, GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, the Netherlands.
authors.forename: Colinda C J M
authors.initials: CC
authors.lastname: Simons
authors.affiliation: Department of Epidemiology, GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, the Netherlands.
authors.forename: Martien van
authors.initials: Mv
authors.lastname: Dongen
authors.affiliation: Department of Epidemiology, GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, the Netherlands.
authors.forename: Leo J
authors.initials: LJ
authors.lastname: Schouten
authors.affiliation: Department of Epidemiology, GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, the Netherlands.
authors.forename: Bas A J
authors.initials: BA
authors.lastname: Verhage
authors.affiliation: Department of Epidemiology, GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, the Netherlands.
authors.forename: Piet A
authors.initials: PA
authors.lastname: van den Brandt
authors.affiliation: Department of Epidemiology, GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, the Netherlands.
authors.forename: Matty P
authors.initials: MP
authors.lastname: Weijenberg
mesh_terms: D001943:Breast Neoplasms / Q000209:etiology; D031204:Caloric Restriction / Q000009:adverse effects / Q000379:methods; D015179:Colorectal Neoplasms / Q000209:etiology; D005260:Female; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000209:etiology*; D011471:Prostatic Neoplasms / Q000209:etiology; D012044:Regression Analysis; D012306:Risk