2.2. SCIENTIFIC AIMS 5.1 In cross-section (baseline only), determine the association between the gut microbiome and the fecal BA composition in 735 participants of a Phase III trial to prevent CRA, considering the effects of age, sex, diet, and other factors (e.g., smoking, obesity, race/ethnicity and diabetes). 5.2 Test if baseline gut microbiome composition is associated with development of CRA and whether any association between the gut microbiome and CRA is dependent on baseline fecal BA composition, considering the intervention with ursodeoxycholic acid (UDCA). S.S Characterize differences in the gut microbiome and BA compositions in rural and urban dwelling Navajo and relate the findings to those observed in the study of NHWs at risk of CRC. The training component of this aim is for mentee Dr. Yellowhair [mentored by Dr. Thompson] to lead an effort to describe the gut microbiome and BA composition and levels in Navajo, considering urbanization, age, sex, and lifestyle (diet and exercise). 2.3 IMPACT. Identification of the factors (BAs, gut microbiome) that mediate the role of the environment in CRC will allow us to better target and modify the physiological factors that underlie the elevated CRC risk that occurs with modern diet and lifestyle factors. Further, demonstration of shared physiological consequences across NHW and NA populations would vastly enhance our ability to extrapolate findings from one population to another.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
2U54CA143924-06
Application #
8823202
Study Section
Special Emphasis Panel (ZCA1-SRLB-B (O1))
Project Start
2009-09-28
Project End
2019-08-31
Budget Start
2014-09-19
Budget End
2015-08-31
Support Year
6
Fiscal Year
2014
Total Cost
$183,339
Indirect Cost
$59,232
Name
University of Arizona
Department
Type
DUNS #
806345617
City
Tucson
State
AZ
Country
United States
Zip Code
85721
Purohit, Rahul; Fritz, Bradley G; The, Juliana et al. (2014) YC-1 binding to the * subunit of soluble guanylyl cyclase overcomes allosteric inhibition by the * subunit. Biochemistry 53:101-14
Gustafson, Heather L; Yao, Song; Goldman, Bryan H et al. (2014) Genetic polymorphisms in oxidative stress-related genes are associated with outcomes following treatment for aggressive B-cell non-Hodgkin lymphoma. Am J Hematol 89:639-45
Karn, Robert C; Laukaitis, Christina M (2014) Selection shaped the evolution of mouse androgen-binding protein (ABP) function and promoted the duplication of Abp genes. Biochem Soc Trans 42:851-60
Briehl, Margaret M; Tome, Margaret E; Wilkinson, Sarah T et al. (2014) Mitochondria and redox homoeostasis as chemotherapeutic targets. Biochem Soc Trans 42:939-44
Janousek, Vaclav; Karn, Robert C; Laukaitis, Christina M (2013) The role of retrotransposons in gene family expansions: insights from the mouse Abp gene family. BMC Evol Biol 13:107
Nelson-Moseke, Anna C; Jeter, Joanne M; Cui, Haiyan et al. (2013) An unusual BRCA mutation distribution in a high risk cancer genetics clinic. Fam Cancer 12:83-7
Ramanathan, Saumya; Mazzalupo, Stacy; Boitano, Scott et al. (2011) Thrombospondin-1 and angiotensin II inhibit soluble guanylyl cyclase through an increase in intracellular calcium concentration. Biochemistry 50:7787-99