Overweight and Obesity Determine the Risk for Gastrointestinal Cancer in a Sex-Dependent Manner: A Retrospective Cohort Study of 287,357 Outpatients in Germany

SIMPLE SUMMARY: By analyzing a large German primary care provider database, we demonstrated that obesity represents a decisive risk factor for the development of colon, rectal, and liver cancer, partly in a sex-dependent manner. Thus, along with previous data, our study including >280,000 patients suggests that the clinical management of overweight patients should include a careful and structured risk assessment for the development of cancer in order to improve long-term outcomes in these patients. ABSTRACT: Cancer represents the second leading cause of death worldwide, implementing a major health care and socioeconomic burden. Overweight and obesity, both of which are dramatically on the rise in both highly and less developed regions worldwide, have been established as modifiable risk factors for the development of various tumor entities including gastrointestinal (GI) cancers such as colorectal or gastric cancer. However, systematic data on an association between excessive body fat and GI cancer development from Germany are missing. Methods: A total of 287,357 adult outpatients with an available BMI value between 2010 and 2019 were identified from the Disease Analyzer database (IQVIA). The main outcome was the association between pre-obesity (BMI 25–30 kg/m(2)) and obesity (BMI ≥ 30 kg/m(2)) compared to normal weight (BMI 18.5–25 kg/m(2)) and the incident of a GI cancer diagnoses (including colon, rectum, stomach, pancreas, and liver cancer). Results: Within the observation period, the proportion of colon cancer patients increased stepwise from 0.5% and 0.64% in normal weight to 0.71% and 0.91% in obese female and male patients, respectively, which was confirmed in multivariable regression models (OR(female obesity): 1.23; 95% CI: 1.03–1.48; OR(male obesity): 1.43, 95% CI: 1.17–1.74). In contrast, multivariable regression models revealed that obesity was significantly associated with rectal cancer (OR: 1.36, 95% CI: 1.01–1.84) as well as liver cancer (OR: 1.79, 95% CI: 1.17–2.73) in men only. Conclusions: Our data suggest that obesity represents a decisive risk factor for the development of colon, rectal, and liver cancer, partly in a sex-dependent manner. Since overweight and obesity are modifiable risk factors, the current results may help to establish appropriate prevention and lifestyle programs to reduce both the incidence as well as the high morbidity and mortality of GI tumors in the future.