Date on Master's Thesis/Doctoral Dissertation


Document Type

Doctoral Dissertation

Degree Name

Ph. D.


Epidemiology and Population Health

Committee Chair

Baumgartner, Kathy B.

Author's Keywords

Breast cancer; Ethnicity; Epidemiology; Polymorphisms


Breast--Cancer--Genetic aspects; Breast--Cancer--Epidemiology


Polymorphisms in the adrenergic receptor beta-2 (ADRB2) gene have been studied in relation to risk of Type 2 diabetes and obesity, but few studies have investigated associations with breast cancer. The purpose of this research was to evaluate the primary hypothesis that ADRB2 variants (rs1042713-Arg16Gly and rs1042714-Gln27Glu) are associated with breast cancer risk in non-Hispanic white (NHW) and Hispanic (H) women using data from a population-based case-control study conducted in the southwestern United States: 'The 4-Corners Breast Cancer Study'. A total of 1,244 NHW and 606 H cases with incident primary breast cancer were ascertained and 1,330 NHW and 728 H population-based controls were selected. Information on lifestyle and physical activity, diet, demographics, and reproductive background was collected through an in-person questionnaire, and blood samples were taken for genetic analyses from consenting participants. ADRB2 genotypes for rs 1042713 and rs 1042714 were determined using PCR. Each genotype as well as their haplotypes was evaluated in multi variable logistic regression models to estimate the associations with breast cancer risk, while adjusting for potential confounders, including study center, history of diabetes, body mass index, genetic admixture, and menopausal status. ADRB2 genotype frequencies were significantly different between NHW and H women. Individually, the ADRB2 polymorphisms were not associated with breast cancer in either ethnic group. However, having 2 copies compared to one or zero copies of the ADRB2 G-G haplotype was associated significantly with increased risk of breast cancer among NHW women [odds ratio (OR), 1.95; 95% confidence interval (95% CI), 1.26-3.01] but reduced risk among Hispanic women [OR, 0.74; 95% CI, 0.50-1.09], (p-for interaction= 0.004). Risk was significantly decreased in Hispanic women with a history of Type 2 diabetes and 2 copies of the G-G haplotype [OR, 0.33; 95% CI, 0.12-0.92] while the association was increased, but not statistically significant among NHW women, [OR, 4.91; 95% CI, 0.52-46.60], (p-for interaction = 0.025). While the interaction between obesity (body mass index (BMI) ~ 30 kg/m2) and the G-G haplotype was not significant (p= 0.200), the association in NHW obese women with 2 copies of the G-G haplotype was similarly increased [OR, 3.01; 95% CI, 1.22-7.44], but decreased in Hispanics [OR, 0.42; 95% CI, 0.20-0.56]. These data suggest that ethnicity modifies the association between the ADRB2 G-G haplotype and breast cancer risk and history of Type 2 diabetes and obesity enhances the divergence of risk between Hispanic and NHW women.