A possible link between famine exposure in early life and future risk of gastrointestinal cancers: Implications from age-period-cohort analysis.

The Chinese famine in 1958-1962 was one of the worst in human history, but its potential influence on cancer risks is uncertain. Using cancer incidence data in Shanghai, China, during 1983-2007, we calculated age-specific incidence rates of gastrointestinal cancers in birth cohorts exposed to the Chinese famine in different periods of life and a non-exposed reference cohort. Age-period-cohort regressions estimated the overall relative risks of gastrointestinal cancers in each birth cohort. A total of 212,098 new cases of gastrointestinal cancer were identified during the study period (129,233 males and 82,865 females), among whom 18,146 had esophageal cancer, 71,011 gastric cancer, 55,864 colorectal cancer, 42,751 liver cancer, 9,382 gallbladder cancer, and 14,944 had pancreatic cancer. The risk of esophageal, gastric, colorectal, and liver cancers was higher in cohorts exposed to the Chinese famine in early life than in the reference cohort, except for esophageal cancer in women. The risk of esophageal, liver, and colorectal cancers was particularly high in men exposed to famine during early childhood (0-9 years). There were no clear associations between famine exposure and the risk of pancreatic or gallbladder cancer. This study suggests an increased risk of esophageal, gastric, liver, and colorectal cancers associated with childhood exposure to the Chinese famine. These findings indicate a need for further investigations confirming the results and identifying the underlying mechanisms. The fetal origin hypothesis, also known as “Barker's hypothesis” or “thrifty phenotype hypothesis”, postulates that fetal undernutrition leads to restricted fetal growth metabolic adaptations, which may result in increased risk of chronic diseases later in life 1, 2. Famines can be seen as natural experiments that can provide unique opportunities to investigate the long-term health effects of nutritional deprivation during fetal life and early childhood. Previous famine studies have examined associations between famine exposure in early life and risks of a variety of common diseases during adulthood, including hypertension 3, obesity 4, type 2 diabetes and other metabolic disorders 5-7, and respiratory diseases 8. However, only a limited number of studies, mostly from Europe, have addressed the risk of cancer in adulthood associated with famine exposure in early life, and these provided inconsistent results 9-15. This article is protected by copyright. All rights reserved.