Maternal obesity and the intergenerational risk of cancer: Epidemiologic evidence and mechanistic insights

Over recent decades, the prevalence of obesity has markedly surged. While excess maternal weight is a well-established risk factor for adverse pregnancy outcomes, growing evidence suggests that maternal obesity may also increase the long-term risk of cancer in offspring. This comprehensive review synthesizes epidemiological and experimental data linking maternal obesity to heightened cancer susceptibility in the next generation. Observational studies demonstrate increased risks of childhood leukemia and colorectal cancer in offspring of obese mothers, whereas preclinical models support associations with breast, liver, colon, and pancreatic cancers. Mechanistically, maternal obesity induces epigenetic reprogramming, immune dysregulation, and vertical transmission of a dysbiotic gut microbiota, which may lead to persistent alterations in metabolic and inflammatory signaling pathways in offspring, thereby promoting a pro-tumorigenic environment and potentially increasing cancer susceptibility. Given the global burden of obesity, this intergenerational risk has critical public health implications. Lifestyle modifications, weight-loss interventions, and targeted approaches such as probiotic supplementation may offer promising strategies to mitigate cancer risk in offspring, but require scientific confirmation in further studies. Future research should prioritize mechanistic dissection of exposure windows, identification of predictive biomarkers, and the development of effective, scalable preventive therapies.