Genetic Variations in Stem Cell-Related Genes and Colorectal Cancer Prognosis:
Abstract
Background
Many properties of cancer cells are reminiscent of those in normal stem cells. Genes important to stem cell development have
been significantly implicated in the etiology and clinical outcome of colorectal cancer (CRC). However, the associations of
genetic variations in these genes with CRC prognosis have not yet been elucidated.
Results
The most significant finding was related to rs879882, a variant in the 5′ region of POU5F1 gene which encodes a protein essential for embryonic stem cell self-renewal and pluripotency, and induced pluripotent stem
cell reprogramming. The variant-containing genotypes of rs879882 were associated with an increased risk of recurrence (hazard
ratio [HR] = 2.10, 95 % confidence interval [CI] 1.17–3.76, P = 0.01). In chemotherapy-stratified analysis, the association remained borderline significant in patients receiving chemotherapy
(HR = 1.97, 95 % CI 0.89–4.34, P = 0.09). In addition, a nonsynonymous SNP of APC gene was also significantly associated with recurrence risk in chemotherapy-treated patients (HR = 2.63, 95 % CI 1.14–6.06
P = 0.02). Further analyses showed a combined effect of the two SNPs in predicting CRC recurrence in patients receiving chemotherapy
(P = 0.04) but not in those without chemotherapy (P = 0.43). Moreover, an exploratory multivariate assessment model indicated that these two variants enhanced the power to predict
recurrence after chemotherapy.
