Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2015:2015:860405.
doi: 10.1155/2015/860405. Epub 2015 Apr 6.

Variants of SCARB1 and VDR Involved in Complex Genetic Interactions May Be Implicated in the Genetic Susceptibility to Clear Cell Renal Cell Carcinoma

Ewelina Pośpiech  1 , Janusz Ligęza  2 , Wacław Wilk  3 , Aniela Gołas  1 , Janusz Jaszczyński  3 , Andrzej Stelmach  3 , Janusz Ryś  3 , Aleksandra Blecharczyk  1 , Anna Wojas-Pelc  4 , Jolanta Jura  2 , Wojciech Branicki  2
Affiliations
Clinical Trial

Variants of SCARB1 and VDR Involved in Complex Genetic Interactions May Be Implicated in the Genetic Susceptibility to Clear Cell Renal Cell Carcinoma

Ewelina Pośpiech et al. Biomed Res Int. 2015.

Abstract

The current data are still inconclusive in terms of a genetic component involved in the susceptibility to renal cell carcinoma. Our aim was to evaluate 40 selected candidate polymorphisms for potential association with clear cell renal cell carcinoma (ccRCC) based on independent group of 167 patients and 200 healthy controls. The obtained data were searched for independent effects of particular polymorphisms as well as haplotypes and genetic interactions. Association testing implied position rs4765623 in the SCARB1 gene (OR = 1.688, 95% CI: 1.104-2.582, P = 0.016) and a haplotype in VDR comprising positions rs739837, rs731236, rs7975232, and rs1544410 (P = 0.012) to be the risk factors in the studied population. The study detected several epistatic effects contributing to the genetic susceptibility to ccRCC. Variation in GNAS1 was implicated in a strong synergistic interaction with BIRC5. This effect was part of a model suggested by multifactor dimensionality reduction method including also a synergy between GNAS1 and SCARB1 (P = 0.036). Significance of GNAS1-SCARB1 interaction was further confirmed by logistic regression (P = 0.041), which also indicated involvement of SCARB1 in additional interaction with EPAS1 (P = 0.008) as well as revealing interactions between GNAS1 and EPAS1 (P = 0.016), GNAS1 and MC1R (P = 0.031), GNAS1 and VDR (P = 0.032), and MC1R and VDR (P = 0.035).

PubMed Disclaimer

Figures

Figure 1
Figure 1
Interaction dendrogram provided with MDR analysis. Dendrogram interaction graphs are built using hierarchical cluster analysis and illustrate the presence, strength, and nature of epistatic effects. The more the line connecting two factors is moved to the right side, the stronger the interaction effect is. The red line between factors indicates a high degree of synergy whereas the orange line indicates a lesser degree of synergy.
Figure 2
Figure 2
Entropy-based interaction radial graph provided with MDR analysis. Entropy values in the cells of individual factors indicate the main independent effects whereas the entropy values marked on the lines connecting two factors represent the effect of interaction.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Storkel S., Eble J. N., Adlakha K., et al. Classification of renal cell carcinoma: workgroup no. 1. Union Internationale Contre le Cancer (UICC) and the American Joint Committee on Cancer (AJCC) Cancer. 1997;80(5):987–989. - PubMed
    1. Maubec E., Chaudru V., Mohamdi H., et al. Characteristics of the coexistence of melanoma and renal cell carcinoma. Cancer. 2010;116(24):5716–5724. doi: 10.1002/cncr.25562. - DOI - PubMed
    1. Yu M. C., Mack T. M., Hanisch R., Cicioni C., Henderson B. E. Cigarette smoking, obesity, diuretic use, and coffee consumption as risk factors for renal cell carcinoma. Journal of the National Cancer Institute. 1986;77(2):351–356. - PubMed
    1. Chow W.-H., Gridley G., Fraumeni J. F., Järvholm B. Obesity, hypertension, and the risk of kidney cancer in men. The New England Journal of Medicine. 2000;343(18):1305–1311. doi: 10.1056/nejm200011023431804. - DOI - PubMed
    1. Ferlay J., Steliarova-Foucher E., Lortet-Tieulent J., et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. European Journal of Cancer. 2013;49(6):1374–1403. doi: 10.1016/j.ejca.2012.12.027. - DOI - PubMed

Publication types