Genetic polymorphisms by race/ethnicity among colon cancer patients in Los Angeles County.

Abstract

492 Background: Though disparate outcomes in colon cancer may be multifactorial, racial/ethnic disparities persist despite adjusting for these factors. Genetic alterations, including single-nucleotide polymorphisms (SNPs), have been shown to predict treatment response in colorectal cancer. Here, we evaluate the variability of genetic alterations in colon cancer patients by examining SNPs in major racial/ethnic groups. Methods: We obtained 76 normal tissue specimens from colon cancer patients of different race/ethnicity at our institution. DNA was extracted and analyzed for 6 SNPs (MTHFR 677C>T, XRCC1 685C>T, XRCC1 1301G>A, XPD 2282A>C, TP53 215G>C, and CCND1 870G>A) by polymerase chain reaction and direct sequencing. Prevalence of each allelic combination was compared between groups by the chi-square test. Results: Archived colon cancer tissues were obtained from whites, blacks, Hispanics and Asians (n=19 per group). From genotyping, we identified statistically significant differences in prevalence of CCND1 870G>A between groups ( Table , p=0.0428). Specifically, whites and Asians had significantly higher prevalence of CCND1 870G>A than blacks and Hispanics (100% and 94%, vs. 68% and 79%, respectively). Furthermore, whites and Asians were more frequently heterozygous (G/A) for the SNP (89% in both), whereas Hispanics comprised the largest proportion (16%) of patients homozygous for CCND1 870G>A. Overall, the allelic frequency of CCND1 870G>A varied among the racial/ethnic groups. Other SNPs in treatment-related pathways were evaluated, but there was no difference in prevalence of the other 5 SNPs between groups. Conclusions: Our findings demonstrate that detection of specific genetic polymorphisms differs between the major racial/ethnic groups with colon cancer. Differences in the prevalence of CCND1 870G>A, which affects cell-cycle progression, suggests a potential mechanism for disparities in cancer susceptibility and progression. Therefore, identification of such genetic variability may support a genetic basis for racial disparities in cancer outcomes. [Table: see text]