[Background] Loss of genomic imprinting (LOI) of IGF-2 is an independent risk factor for colorectal cancer (CRC), however the LOI-positive CRC phenotype has not been previously characterized.
[Aim] This study determined the clinicopathological characteristics of LOI-positive CRC patients compared to the LOI-negative CRC individuals.
[Patients and Methods] We performed PCR on gDNA and RT-PCR on RNA extracted from normal peripheral blood lymphocytes (PBL) of prospectively recruited RC patients, followed by Apa I digestion. Based on Apa I DNA polymorphism, the informative (heterozygosity) and imprinting status of IGF2 gene were determined. Several clinical and pathological characteristics were evaluated including: age at diagnosis, gender, family history of CRC, tumor stage, differentiation, size, lymph node involvement, and size. Statistical analysis was performed by using logistic regression, Mann Whitney test, Kruskal-Wallis test using STATA 9.0.
[Results] Of 239 patients recruited, 86 were informative based on Apa I DNA polymorphism and eligible for analysis. Fifty-sex patients (22 males; age: 55.7±12.7) were LOI-negative, and 26 patients (13 males, age: 61.6±15.3) were LOI-positive; 39 patients had rectal and 43 patients had colon cancer. The odds ratio for the association of LOI of IGF2 with CRC was 5.3 (95% CI 2.3-11.7), 6.04 (95% CI 2.27-16.3), and 3.94 (95% CI 1.36 - 11.4) for all CRC, rectal, and colonic cancer, respectively. Evaluation of the clinicopathological characteristics was performed for all CRC cases, and separately for rectal and colon cancer. No statistically significant difference for any of the characteristics evaluated was found in patients with rectal cancer. However, among patients with colon cancer, LOI-positive patients were diagnosed at a younger age (64.9±11.6 vs. 56.1±11.4, p = 0.04), and had significantly advanced cancer stage (Dukes D: 57% vs. 10%, p= 0.03).
[Conclusion] LOI-positive colon cancer patients presents at a significantly younger age and with an advance stage of disease, compared to LOI-negative patients. Moreover, colon cancer LOI-positive patients appear to have distinct genotype-phenotype characteristics compared to rectal cancer LOI-positive patients. These findings suggest a distinct carcinogenic pathway for LOI-positive patients, which may have implications in screening and risk assessment. >[Support] NIH grants K07 CA092445 and P50 CA-62924-10, The John G. Rangos, Sr. Charitable Foundation, The Cancer Research and Prevention Foundation, The Eleanor Naylor Dana Charitable Trust and The Clayton Fund.
98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA