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Genetic Variations in Stem Cell-Related Genes and Colorectal Cancer Prognosis

  • Original Research
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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.

Methods

We analyzed the effects of eight potentially functional single nucleotide polymorphisms (SNPs) in six stem cell-related genes on the prognosis of a well-characterized population of 380 Chinese CRC patients diagnosed from February 2006 to January 2010.

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.

Conclusion

We presented one of the first epidemiologic studies showing that stem cell-related genetic variants may impact CRC clinical outcomes, especially in chemotherapy-treated patients.

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Acknowledgments

The work reported here was supported by a start-up grant from Thomas Jefferson University, grant 2009CB521704 from The National Basic Research Program of China, and grant 30872927 from the National Natural Science Foundation of China.

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Authors and Affiliations

  1. Division of Population Science, Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, 1025 Walnut Street, Room 1015, Philadelphia, PA, 19107, USA

    Hushan Yang & Ronald E. Myers

  2. Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi’an, 710032, China

    Falin Qu & Guoqiang Bao

  3. Department of Experimental Therapeutics, Department of Medicine, Thomas Jefferson University, Philadelphia, PA, 19107, USA

    Terry Hyslop

  4. Stem Cell Biology Group, Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Science, Research Triangle Park, NC, 27009, USA

    Guang Hu

  5. State Key Laboratory of Cancer Biology, Cell Engineering Research Centre & Department of Cell Biology, Fourth Military Medical University, Xi’an, 710032, China

    Fei Fei & Jinliang Xing

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  1. Hushan Yang
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Correspondence to Hushan Yang.

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ESM 1

(DOC 31 kb)

Supplementary Table 1

Stem cell-related genes and polymorphisms evaluated in this study (DOC 42 kb)

Supplementary Table 2

Demographic and clinicopathological characteristics of patients with colorectal cancer (DOC 69 kb)

Supplementary Table 3

Joint effects between rs8798822 and rs459552 risk genotypes in recurrence of colorectal cancer patients stratified by chemotherapy (DOC 42 kb)

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Yang, H., Qu, F., Myers, R.E. et al. Genetic Variations in Stem Cell-Related Genes and Colorectal Cancer Prognosis. J Gastrointest Canc 43, 584–593 (2012). https://doi.org/10.1007/s12029-012-9388-z

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