African Americans are disproportionately burdened by colorectal cancer, the third most commonly diagnosed cancer and the third leading cause of cancer death among men and women in the United States. The highest colorectal cancer incidence and mortality rates are observed among African Americans, compared to other racial/ethnic groups. Furthermore, African Americans are more likely to develop large, more-advanced colorectal adenomas, the primary premalignant lesion of colorectal cancer, which have greater potential to progress into colorectal cancer. Reasons for the increased risk of colorectal cancer and elevated occurrence of high-risk adenomas in this racial group have not been completely elucidated. This indicates that more research is needed to better understand the etiology of colorectal cancer and adenoma among African Americans and identify potential prevention strategies that could reduce the cancer burden. In this dissertation, I analyzed two potential risk factors for colorectal cancer, low vitamin D status and circadian disruption, and a potential preventive factor for colorectal adenoma, use of aspirin or non-aspirin NSAIDs, among a group of African American women. For all three analyses, I utilized data from the Black Women’s Health Study, an ongoing prospective cohort study of African American women begun in 1995.
Prior studies among mostly White populations, indicate that low vitamin D levels increase risk of colorectal cancer. African Americans tend to have lower vitamin D levels compared to other populations. In my first dissertation study, I assessed the relation of vitamin D status with colorectal cancer risk using predicted vitamin D score, derived from a previously validated vitamin D prediction model, as a proxy measure for vitamin D status. Using Cox proportional hazards regression to estimate hazard ratios (HR) and 95% confidence intervals (CI), I found that women in the lowest quartile of predicted vitamin D score were estimated to have a 41% (HR=1.41, 95% CI 1.05–1.90) increased risk of colorectal cancer compared to those in the highest quartile. Predicted vitamin D score was similarly associated with colon (HR for lowest vs. highest quartile=1.44, 95% CI 1.02–2.01) and rectal cancer (HR=1.34, 95% CI 0.70–2.56). The association was not modified by age, BMI, or supplemental vitamin D intake. My findings suggest that low vitamin D status may contribute to the disproportionately high incidence of colorectal cancer among African Americans and higher vitamin D status may reduce incidence.
Research shows that disruption of the human circadian clock can have carcinogenic consequences. African Americans, who have shorter endogenous circadian periods, sleep less, and often have less flexible work schedules may be more susceptible to this disruption. In my second study, I examined the impact of two novel markers of circadian disruption, chronotype and residential position within a time zone, on colorectal cancer risk, using Cox proportional hazards regression. I found that neither marker (evening vs. morning chronotype: HR=0.96, 95% CI 0.73–1.27; Per 5-degree longitude increment in residential position from eastern to western border of time zone: HR=0.92, 95% CI 0.82–1.03) was associated with colorectal cancer, overall or within strata of age, geographic region, BMI, night shift work, or latitude. These results suggest that chronotype and residential position in a time zone may not be associated with an increased risk of colorectal cancer in African American women. However, more research on these novel markers is necessary.
Accumulating evidence suggests that use of aspirin or non-aspirin NSAIDs is associated with a reduced occurrence of colorectal adenoma, but few studies have explored associations among African Americans. Thus, in my third study, I analyzed aspirin or non-aspirin NSAID use in relation to colorectal adenoma occurrence using logistic regression for longitudinal data. Aspirin use was associated with a reduced odds of adenoma (OR=0.88, 95% CI 0.76–1.02). The association was stronger for rectal adenoma (OR=0.63, 95% 0.37–1.06) and adenomas <1 cm in size (OR=0.83, 95% 0.70–0.97). In contrast, non-aspirin NSAID use was associated with an increased odds of adenoma (OR=1.20, 95% 0.99–1.45), particularly adenoma in the proximal colon (OR=1.30, 95% CI 1.04–1.61) and adenomas <1 cm in size (OR=1.31, 95% CI 1.07–1.61). My findings suggest that aspirin use may be a useful strategy to reduce adenoma occurrence among African Americans. The unexpected positive association between non-aspirin NSAIDs and adenoma warrants further study.
Findings from this dissertation suggests that low vitamin D status may contribute to the disproportionate burden of colorectal cancer among African Americans, while aspirin use may help reduce the burden. / 2025-01-31T00:00:00Z
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/43689 |
| Date | 24 January 2022 |
| Creators | Barber, Lauren Elizabeth |
| Contributors | Palmer, Julie R. |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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