Abstract A82: The FTO obesity gene and the risk of postmenopausal breast cancer among the medically underserved population in rural Pennsylvania
Authors: Smelser Diane T. , Gerhard Glenn S. , Patel Nikita , Golden Alicia , Stark Azadeh 
Published: December 2010

Purpose: Among all the established risk factors for postmenopausal breast cancer (PMBC), obesity, with 21 % risk, accounts for the largest share of potentially modifiable population attributable risk (PAR). The risk of PMBC from obesity is multifactorial and includes genetic, behavioral and environmental influences. Of all the genes associated with obesity, FTO has the highest risk (RR=1.67) and greatest PAR (&gt; 20%), in the white European population. The risk of human adiposity has been associated with allele A (Adenine) in SNP rs9939609, and G (Guanine) in SNP rs1477196 and T(Thymidine) in SNP rs1861868. Central and northeastern counties in Pennsylvania (PA), of which 75% has been designates as medically underserved, is home to a relatively homogenous population of white European ancestry. This region experiences significantly above the national average age-adjusted breast cancer incidence and high prevalence of obesity. Elimination of health disparities across different segments of population is one of the objectives of the Healthy People of 2010. The notion of health disparities implies that the disease-specific risk for different sub-populations should be identified and resources should be allocated accordingly. Research on the genetic susceptibility of PMBC from obesity has been inconclusive. Therefore, we conducted a retrospective study with the primary objective of assessing prevalence of three SNPs [rs9939609, rs1861868, and rs1477196] of the FTO gene in group of women diagnosed with invasive breast cancer and their age-matched controls.

Methods: The study benefits from an ongoing population-based biobanking project entitled “MyCode” at the GHS. A total of 201 women diagnosed with invasive breast cancer have donated blood samples to the project constitute the cases. Controls were 603 women with no medical history of breast cancer, who have also participated in the biobanking. SNPs have been genotyped using ABI TaqMan assays. Clinical and demographic data have been retrieved from medical records. Measures of associations were estimated using non-parametric statistics. All statistical analyses were performed using SAS v. 9.1 (SAS Institute, Cary, NC).

Results: So far genotyping has been completed for a total of 50 cases and 99 controls with the mean age of 66 (±12) and 64 (±11) (P=.49) years, respectively. The difference in mean BMI between cases (32.23 ±7.23) and controls (33.52 ± 8.80) did not reach the level of statistical significance. Of the three SNPs, the SNP rs9939609 yielded a potential association with PMBC (OR= 2.04,95% CI .96-4.34, P=.0653).

Conclusions: Preliminary findings suggest that one of the SNPs of FTO might increase the risk of PMBC. The FTO gene, in addition to its role in human adiposity, has been reported to encode a protein that is a member of the non-heme dioxygenase super family, involved in DNA repair pathway by reversing of alkylated damages to DNA and RNA. Discerning the association between the common SNPs of the FTO gene and PMBC offers the potential to identify at risk women that could benefit from targeted intervention strategies to reduce their risk of PMBC.

Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):A82.