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The C/A polymorphism in intron 11 of the XPC gene plays a crucial role in the modulation of an individual’s susceptibility to sporadic colorectal cancer

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Abstract

Epidemiological data show that colorectal cancer (CRC) is the second most frequent malignancy worldwide. The involvement of “minor impact genes” such as XME and DNA-repair genes in the etiology of sporadic cancer has been postulated by other authors. We focused on analyzing polymorphisms in DNA-repair genes in CRC. We considered the following genes involved in DNA-repair pathways: base excision repair (OGG1 Ser326Cys, XRCC1 Trp194Arg and Arg399Gln); nucleotide excision repair [XPA (−4)G/A, XPC C/A (i11) and A33512C (Lys939Gln), XPD Asp312Asn and A18911C (Lys751Gln), XPF Arg415Gln, XPG Asp1104His, ERCC1 C118T]; homologous recombination repair [NBS1 Glu185Gln, Rad51 135G/C, XRCC3 C18067 (Thr241Met)]. The study group consisted of 133 patients diagnosed with sporadic CRC, while the control group was composed of 100 age-matched non-cancer volunteers. Genotyping was performed by PCR and PCR-RFLP. Fisher’s exact test with a Bonferroni correction for multiple testing was used. We found that: (i) XPC C/A (i11) heterozygous variant is associated with increased risk of CRC [OR is 2.07 (95% CI 1.1391, 3.7782) P = 0.038], (ii) XPD A18911C (Lys751Gln) is associated with decreased risk of CRC [OR = 0.4497, (95% CI 0.2215, 0.9131) P = 0.031] for an individual with at least one A allele at this locus. (1) The XPC C/A (i11) genotype is associated with an increased risk of sporadic colorectal cancer. (2) The NER pathway has been highlighted in our study, as a most important in modulation of individual susceptibility to sCRC.

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Acknowledgments

This study has been supported by the State Committee for Scientific Research, Polish Ministry for Scientific Research and Information Technology (Grant no. 1423/P01/2007/32), 2007–2010. David Ramsey is supported by Science Foundation Ireland (SFI) as part of the BIO-SI project.

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Authors and Affiliations

  1. Department of Genetics, Medical University of Wroclaw, Marcinkowskiego 1, 50-368, Wroclaw, Poland

    Justyna Gil, Agnieszka Stembalska, Pawel Karpinski, Karolina A. Pesz, Izabela Laczmanska, Przemyslaw Leszczynski & Maria Malgorzata Sasiadek

  2. Department of Mathematics and Statistics, University of Limerick, Limerick, Ireland

    Dave Ramsey

  3. 2nd Department of General and Oncological Surgery, Medical University, Wroclaw, Poland

    Zygmunt Grzebieniak

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  1. Justyna Gil
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  2. Dave Ramsey
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  3. Agnieszka Stembalska
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  4. Pawel Karpinski
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Correspondence to Justyna Gil.

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Gil, J., Ramsey, D., Stembalska, A. et al. The C/A polymorphism in intron 11 of the XPC gene plays a crucial role in the modulation of an individual’s susceptibility to sporadic colorectal cancer. Mol Biol Rep 39, 527–534 (2012). https://doi.org/10.1007/s11033-011-0767-5

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