Abstract 5362: Analysis of loss of IGF2 genomic imprinting and colorectal cancer risk in Puertorrican Hispanics.

Background: Loss of genomic imprinting (LOI) of IGF-2 has been proposed as an independent risk factor for colorectal cancer (CRC) for Non-Hispanic Whites (NHW) and Asians. However, whether the same association between LOI of IGF2 and CRC risk exist in Hispanics is unknown. Aim: This study aimed at determining the association of LOI of IGF2 in peripheral blood lymphocytes and CRC risk in Hispanics. As a secondary aim we evaluated the clinicopathological characteristics of LOI-positive CRC patients compared to the LOI-negative CRC individuals. Methods: Prospectively recruited patients were classified as informative (heterozygosity for Apa I DNA polymorphism) using TaqMan® SNP Genotyping Assay (Applied Biosystems) on gDNA extracted from peripheral blood lymphocytes. cDNA was synthesized and the imprinting status of IGF2 gene was determined using the same methodology in informative all patients. Demographic, clinical and pathological characteristics were evaluated including: age at diagnosis, gender, tumor size, TNM stage, and differentiation. Statistical analysis was performed using conditional multiple logistic regression models, Odds Ratios (OR) and 95% CI were calculated using STATA 10.0. Results: A total of 587 patients were recruited and analyzed. The cohort was comprised of 359 controls (61.26%) and 227 CRC patients (38.74%) with a mean age 62.1 (range 21-85); and 385 (65.5%) female). Apa 1 analysis identified 222 informative subjects of which 66 individuals had LOI of IGF2 in their PBLs. LOI of IGF2 was not statistically associated with colorectal neoplasia (OR=1.07, 95% CI:0.57-1.99). Furthermore, gender, age at diagnosis of CRC, tumor location, development of prostate, breast or other cancers, and family history of other cancers is not associated with LOI of IGF2. Multiple logistic regression model analysis for the association of CRC and LOI showed that family history of CRC was independently associated with having a personal history of CRC (OR=1.82,95% CI:1.02-3.25). Conclusion: LOI of IGF2 was not independently associated with CRC, colonic adenomas or any of the other cancers examined in this Hispanic cohort. Family history of CRC was the only independent risk factor associated with personal history of CRC. Perhaps other genetic/epigenetic, environmental factors than the ones considered in this study may play a role in the pathogenesis on CRC in the Puerto Rican Hispanic population. Further analysis on genomewide methylation panels is underway to examine the role of epigenetics among Hispanics with CRC. Citation Format: Maria Gonzalez-Pons, Mercedes Y. Lacourt, Sharon Fonseca-Williams, Lorena Marcano, Xiomara Castillo, Ronghua Zhao, Raul Bernabe-Dones, Marcia Cruz-Correa. Analysis of loss of IGF2 genomic imprinting and colorectal cancer risk in Puertorrican Hispanics. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5362. doi:10.1158/1538-7445.AM2013-5362