Studying neighborhood socioeconomic deprivation and colorectal cancer risk in PLCO
Previous studies in two large US cohorts, the Nurses’ Health Study and the NIH-AARP Diet and Health Study, reported that people living in low SES neighborhoods had a higher risk of developing colorectal cancer. Their findings suggest that neighborhood socioeconomic deprivation may play a role in colorectal cancer disparities. Given the potentially important public health implications, further study is needed not only to confirm the association between neighborhood SES and colorectal cancer risk, but also to investigate the underlying mechanisms through which neighborhood environment exerts its health effects.
Neighborhood socioeconomic deprivation may have an impact on colorectal cancer risk through two different yet interconnected pathways: through unhealthy behaviors and stress-induced alterations in immune system. Low SES neighborhoods have been linked with lack of physical activity, poor diet, and obesity. On the other hand, deprived neighborhoods also create a stressful environment, and exposure to chronic stress can lead to impaired immune function. Both unhealthy behaviors and altered immune system in response to stress may lead to chronic inflammation, immune dysregulation, and metabolic disorders, all of which have been shown to promote the development of colorectal cancer.
I propose to study baseline neighborhood socioeconomic deprivation and colorectal cancer risk in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO). I will apply a comprehensive framework to further investigate the multiple mechanisms that may mediate the effects of neighborhood deprivation on colorectal cancer risk. I am planning to submit an R03 grant to the NCI in the near future to obtain funding to support the following specific aims (see below).
In 2016, I submitted a CDAS request (PLCO-154) to obtain data and perform preliminary analysis for my NIH grant application. My 2016 request was subsequently approved, and I have access to HSQ, SQX and census variables from 2000 census, 2010 census and ACS 5-year summary file (2006-2010) linked to the 2010 addresses.
The current request serves as an update of the earlier request. Once the reconstruction of residential history is completed, I would like to request 1990 and 2000 census data to be linked to the baseline addresses. I would also like to request data on inflammatory markers from the CRC case-control study once they become publicly available after the initial study is published.
Aim 1 Examine the prospective relationship between baseline neighborhood socioeconomic deprivation and risk of colorectal cancer
I will examine baseline (1992-2001) neighborhood socioeconomic deprivation at census-tract level in relation to colorectal cancer risk. Recently, reconstruct residential history from 1990-2010 became available for over 80,000 PLCO participants using the service provided by LexisNexis. Based the preliminary results and early literature, I hypothesize that higher baseline neighborhood deprivation is associated with a higher incidence of colorectal cancer.
Aim 2 Study the pathways linking neighborhood socioeconomic deprivation to colorectal cancer risk
Aim 2.1 Evaluate the role of lifestyle factors in mediating the effect of neighborhood deprivation on colorectal cancer risk
I will examine the relationship between neighborhood deprivation and established risk factors of colorectal cancer (diet, physical activity, obesity, NSAID use, alcohol intake, etc.). I will also use mediation analysis to examine to what extent the association between neighborhood deprivation and colorectal cancer risk is driven by lifestyle factors. I hypothesize that 1) neighborhood deprivation is associated with less healthy lifestyle choices; and 2) lifestyle factors partially mediate the neighborhood effects on colorectal cancer risk.
Aim 2.2 Evaluate the role of inflammation in the relationship between neighborhood deprivation and colorectal cancer risk
In a nested-case control study, I will examine the relationship between neighborhood SES and levels of over 70 serum inflammation markers. I will also explore the possible mediating role of inflammation markers in the potential relationship between neighborhood socioeconomic deprivation and elevated risk of colorectal cancer.
Dong Zhang, University of Iowa