Genetic variants in obesity-related genes are associated with tumor recurrence in stage II/III colon cancerGenetic variants in obesity-related genes are associated with tumor recurrence in stage II/III colon cancer

Robert D. Ladner1, Armin Gerger1, Wu Zhang1, Melissa J LaBonte1, Dongyun Yang2, Felicitas Lenz1, Cosima Lenz1, Pierre Bohanes1, Yan Ning1,Thomas Winder1, Peter M Wilson1, Leonor Benhaim1, Rita El-Khoueiry1, Anthony El-Khoueiry1, Syma Iqbal1, and Heinz-Josef Lenz1,2

1. Department of Medical Oncology, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA 2. Department of Preventive Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA

Either blood or FFPE tissue specimens were obtained from 234 patients (107 females and 127 males; median age 59 years (range 22–78 years)) with stage II (105 patients) or III (129 patients) colon cancer at the University of Southern California/Norris Comprehensive Cancer Center. The median follow-up was 4.4 years. Obesity-related gene polymorphisms were determined by PCR-RFLP or PCR-based direct sequence. The primary endpoint of the study was time to tumor recurrence (TTR).

High body mass index (BMI) is an established risk factor for colorectal cancer incidence and death. Recent studies found obesity before the diagnosis of colon cancer was associated with worse survival compared with normal weight. Single nucleotide polymorphisms (SNPs) of obesity-related gene have been related with different cancer risk including colorectal cancer. Here we tested the hypothesis whether SNPs in obesity-related genes (PPAR, LEP, NFKB, CD36, DRG1, NGAL, REGIA and DSCR1) maypredict tumor recurrence in stage II/II adjuvant colon cancer

Our preliminary results demonstrated polymorphisms in obesity-related gene might be potential molecular markers to predict TTR in adjuvant colon cancer. Further large and biomarker embedded trial needed to confirm our finings.

In univariable analysis, PPAR rs1801282 and DSCR1 rs6517239 were independently associated with time to tumor recurrence (TTR). Patients with PPAR CC genotype had longer median TTR 9.4 months (95% C.I: 5.6, 12.4+) compared to those with CG genotype, had median TTR 3.4 months (95% C.I: 1.7, 16.8+)(p=0.04, log-rank test). Patients with DSCR1 AA genotype had shorter median TTR 6.6 months (95% C.I: 4.0, 16.8+) compared to those with AG and GG genotypes, which had longer median TTR 9.4 months (95% C.I: 5.7, 10.7+)(p=0.027, log-rank test). The multivariate analysis adjusting for stage and type of adjuvant therapy showed a trend in the association between PPAR rs1801282 and DSCR1 rs6517239 and time to recurrence (Wald test p=0.08 and 0.058, respectively).

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Methods

Baseline patient characteristics