490 Loss of IGF2 Genomic Imprinting and Cancer Risk in An Ethnically Diverse Population

Abstract

[Background] Loss of genomic imprinting (LOI) of IGF-2 is an independent risk factor for colorectal cancer. However, whether LOI of IGF-2 is a risk factor for other malignancies remains unclear. [Aim] The aim of this study was to determine if LOI of IGF-2 was associated to prevalent cases of breast, prostate, colorectal cancer (CRC)and other non-colorectal cancers. [Patients and Methods] Consecutive patients who underwent colonoscopic examination at three Academic Centers were recruited. We performed PCR on gDNA and RT-PCR on RNA extracted from normal peripheral blood lymphocytes (PBL) of prospectively recruited patients, followed by ApaI digestion. Based on ApaI DNA polymorphism, the informative (heterozygosity) and imprinting status of IGF2 gene were determined. Statistical analysis was performed using multiple logistic regression models, Odds Ratios (OR) and 95% CI were calculated with STATA 9.0. [Results] A total of 367 informative patients (based on ApaI DNA polymorphism) were recruited; mean age 56.4 (range 21-85); 166(45%) female; and Hispanic 73(20%). Based on baseline colonoscopy and review of medical records, there were 164 (44.7%) controls and 128 prevalent cancer patients including: colon (112), rectal (33), breast (15), prostate (15), other non-CRC (22). LOI-positive individuals had statistically significant OR for colon, rectal, breast, non-colorectal cancers (See Table below). LOI-positive patients had a borderline increased risk for prostate cancer (OR = 1.73, 95% CI 0.88-6.31) compared to LOI-negative patients. [Conclusion] LOI-positive individuals had a statistically significant 2-3 fold increased risk of having colon, rectal, breast and non-CRC cancers compared to LOI-negative individuals. LOI of IGF2 might be a biomarker for cancer risk, and perhaps may be in the carcinogenic pathway of multiple epithelial neoplasias. [Support] NIH grants K22 CA-, U54 CA-096297, RCMI and P50 CA-62924-10, The Doris Duke Charitable Foundation, The John G. Rangos Sr. Charitable Foundation, and The Clayton Fund. Loss of Imprinting and Cancer Risk