Do adipokines mediate the association between obesity and adenomatous colon polyps?
Cannioto, Rikki A.
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Epidemiological evidence demonstrating an association between obesity and colorectal cancer and adenomatous colon polyps is consistent, yet the biological mechanisms underlying the association are not fully understood. Adipokines have been studied extensively as potential contributors in the obesity-cancer pathway, likely owing to their strong correlation with adipose tissue as well as their inflammatory properties and involvement with cell growth and death. The primary aims of this thesis are to 1) identify group differences in adiponectin and leptin concentrations based upon case status, race, sex, menopausal status and obesity status; 2) determine which proxy measure of adiposity is most strongly associated with adiponectin and leptin concentrations for each race and sex subgroup; and 3) assess whether adiponectin and leptin mediate the relationship between adiposity and adenomatous polyps in a study of African American (AA) and Caucasian men and women. We utilized three proxy measures of adiposity including body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) to explore these relationships. Obesity was defined as a BMI ≥ 30 kg/m 2 and abdominal obesity was defined as having a WC>88 cm in women or WC>102 cm in men. Participants missing anthropometric data and biomarker data (adiponectin and leptin) were excluded. A total of 1420 participants met the criteria for inclusion in the analysis; N=553 AA participants (175 cases and 378 controls) and N=867 Caucasian participants (217 cases and 650 controls). Per aim 1 above, we observed statistically significantly lower adiponectin concentrations among men vs. women, African Americans vs. Caucasians, cases vs. non-cases, non-obese vs. obese and pre-menopausal women vs. post-menopausal women. We also observed statistically significantly higher leptin concentrations in women vs. men, African Americans vs. Caucasians, obese vs. non-obese and post-menopausal women vs. pre-menopausal women. Per aim 2, race and sex differences were observed in the nature and magnitude of associations between the three proxy measures of obesity (BMI, WC, and WHR) and adipokine concentrations. Specifically, among women, WC was the measure of adiposity most strongly associated with adiponectin (-0.30 among AA women and -0.39 for Caucasian women). However, among men, BMI was most strongly correlated with adiponectin among Caucasian men, but there was no association between adiponectin and any measure of adiposity in AA males. Conversely, BMI was most strongly correlated with leptin for AA women, Caucasian women, and Caucasian men (r=0.76, r=0.81, and r=0.73, respectively), while WC was the adiposity measure most strongly correlated with leptin in African American males (r=0.73). Per aim 3, contrary to our hypothesis that leptin and adiponectin mediate the association between obesity and adenomatous colon polyps, we found no evidence that would identify leptin as a mediating variable in the obesity-colorectal adenoma pathway. However, we observed some evidence that adiponectin mediates the association between measures of abdominal obesity and adenomatous colon polyps in Caucasian women. Further studies of the association between obesity, adipokines and colorectal neoplasia—and how these associations may vary by race, sex and obesity are needed to further elucidate whether or not adiponectin and leptin serve as mediators in the association between obesity and adenomatous colon polyps.