Characterizing Leading Risk Factors Contributing to the Racial Disparity of Gallbladder Cancer Incidence Rate in Maricopa County, Arizona

Characterizing Leading Risk Factors Contributing to the Racial Disparity of Gallbladder Cancer Incidence Rate in Maricopa County, Arizona Characterizing Leading Risk Factors Contributing to the Racial Disparity of Gallbladder Cancer Incidence Rate in Maricopa County, Arizona Characterizing Leading Risk Factors Contributing to the Racial Disparity of Gallbladder Cancer Incidence Rate in Maricopa County, Arizona This pilot study has two Specific Aims: Aim-1 to identify modifiable risk factors contributing to the persistent racial disparity of gallbladder cancer (GbCa) incidence, and Aim-2 to characterize a prominent risk factor for GbCa, namely, gallstone disease. The overarching goal of the two interrelated aims is to lay a foundation for developing effective strategies in early diagnosis and timely treatment of GbCa in high-risk populations. Gallbladder cancer presents one of the greatest racial disparities of cancer burden in the U.S., with American Indian (AI) people at a 6- fold or higher incidence rate than non-Hispanic Whites (NHW). This disparity has been known for half a century, especially in Alaska and the Southwest Region of the U.S.; based on our recent systematic literature review and meta-analysis, however, no significant progress in reducing this disparity has been reported. Major risk factors have been recognized including a history of cholelithiasis (formation of gallstones) and type II diabetes (DM-II); being AI, female, obese or overweight; and a family history of GbCa and cholelithiasis. Noticeably, several of these risk factors are modifiable through medical and behavioral interventions. Aim-1 will identify the top three modifiable factors that contribute to the persistent racial disparity of GbCa incidence. We will focus on Mayo Clinics catchment area population in Arizona, i.e., Maricopa County, using 225 de-identified GbCa patients (45 AIs and 180 NHWs 1:4 matched on age and sex). Our primary objective is to identify the actionable targets in reducing GbCa burden among high-risk individuals. Gallstones, where stones are formed in the gallbladder, liver or bile duct, occur in up to 80% of GbCa patients and particularly in older women of AI and Hispanic origin, and cholelithiasis is a common medical condition in U.S. adults. Besides the morbidity and mortality associated with cholelithiasis itself, the excessive risk of digestive system cancers in gallstone carriers is remarkable, specifically, 3-10 times higher risk of GbCa, 2-4 times of liver cancer, and 1.2-2 times of other digestive system cancers. Even among asymptomatic individuals harboring gallstones, an overall 50% increased risk of cancer was reported. Aim-2 will focus on gallstones utilizing the Mountain Park Biobank with patients clinical and epidemiologic questionnaire data resources in Phoenix Arizona, where we will assess plasma metabolome to identify metabolic markers in predicting gallstone phenotypes, and their associations with sex difference in cholelithiasis and GbCa risk.