Abstract 4804: Gallstones, cholecystectomy, and risk of digestive system cancers.
Authors: Nogueira Leticia , Cross Amanda , Freedman Neal , Lai Gabriel , Castro Felipe , Koshiol Jill 
Published: August 2014

Digestive system cancers include cancers of the oral cavity, esophagus, stomach, pancreas, liver, gallbladder, small intestine, colon and rectum, making it the second organ system most commonly affected by cancers in the world. These cancers are among the deadliest cancers worldwide. Gallstones (GS) can lead to inflammation and trauma (which are positively associated with cancer development) in digestive system organs adjacent to the gallbladder. However, the association between gallstones and digestive system cancers outside of the biliary tract has not been well established, especially in the presence of cofounders, such as obesity, physical activity, and alcohol consumption. Cholecystectomy (CH), the most common treatment for GS, can ameliorate inflammation, but has been shown to increase the exposure of the stomach the small intestine to bile. We hypothesized that GS and CH are differentially associated with cancers of the digestive system outside of the biliary tract.

Within the National Institutes of Health-AARP Diet and Health Study (n=487,207) we used Cox proportional hazards regression models adjusted for age, gender, race, smoking, alcohol consumption, body mass index, caloric intake, physical activity, and non-steroidal anti-inflammatory drugs intake to investigate GS (n=30,674) and CH (n=25,457) in relation to cancers of the oral cavity (n=1,004), esophagus (adenocarcinoma n=392 and squamous cell carcinoma n=138), stomach (cardia n=264 and non-cardia n=292), small intestine (n=192), colon (n=3,865), rectum (n=1,410), pancreas (n=1,268), and liver (n=414).

GS were associated with liver cancer [Hazard Ratio = 1.80 (95% confidence interval = 1.37, 2.37)], while CH was not [1.43 (0.83, 2.48)]. In contrast, CH was associated with non-cardia gastric cancer [2.67 (1.45, 4.90)], colon cancer [1.45 (1.29, 1.63)], and esophageal adenocarcinoma [1.74 (1.02, 2.97)] while GS were not [1.31 (0.90, 1.90), 1.06 (0.95, 1.18), and [1.16 (0.81, 1.65)], respectively]. CH was also associated with pancreatic [1.99 (1.49, 2.66)] and small intestine cancer [2.61 (1.61, 4.23), as was GS [1.19 (1.00, 1.43) and 1.61 (1.07, 2.42), respectively]. Neither GS nor CH was associated with oral cavity cancers, esophageal squamous cell carcinoma, or rectal cancer.

A major strength of this large study was the ability to adjust for important cancer risk factors, including tobacco smoking, alcohol intake, and obesity. Nonetheless, future studies are needed to replicate our findings and establish the underlying mechanisms responsible for the identified associations.

Citation Format: Leticia Nogueira, Amanda Cross, Neal Freedman, Gabriel Lai, Felipe Castro, Jill Koshiol. Gallstones, cholecystectomy, and risk of digestive system cancers. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4804. doi:10.1158/1538-7445.AM2013-4804

Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.