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
. 2010 Aug 11:11:123.
doi: 10.1186/1471-2350-11-123.

Genome wide screen identifies microsatellite markers associated with acute adverse effects following radiotherapy in cancer patients

Yuichi Michikawa  1 , Tomo Suga, Atsuko Ishikawa, Hideki Hayashi, Akira Oka, Hidetoshi Inoko, Mayumi Iwakawa, Takashi Imai
Affiliations

Genome wide screen identifies microsatellite markers associated with acute adverse effects following radiotherapy in cancer patients

Yuichi Michikawa et al. BMC Med Genet. .

Abstract

Background: The response of normal tissues in cancer patients undergoing radiotherapy varies, possibly due to genetic differences underlying variation in radiosensitivity.

Methods: Cancer patients (n = 360) were selected retrospectively from the RadGenomics project. Adverse effects within 3 months of radiotherapy completion were graded using the National Cancer Institute Common Toxicity Criteria; high grade group were grade 3 or more (n = 180), low grade group were grade 1 or less (n = 180). Pooled genomic DNA (gDNA) (n = 90 from each group) was screened using 23,244 microsatellites. Markers with different inter-group frequencies (Fisher exact test P < 0.05) were analyzed using the remaining pooled gDNA. Silencing RNA treatment was performed in cultured normal human skin fibroblasts.

Results: Forty-seven markers had positive association values; including one in the SEMA3A promoter region (P = 1.24 x 10(-5)). SEMA3A knockdown enhanced radiation resistance.

Conclusions: This study identified 47 putative radiosensitivity markers, and suggested a role for SEMA3A in radiosensitivity.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Results of two rounds of screening of microsatellite markers for association with radiosensitivity. (A) Results of the screen of the entire genome using 23,244 microsatellite markers and the HGG-1 and LGG-1 pooled DNAs. (B) Results of screening 3,052 markers of interest identified in the preceding genome scan and using the HGG-2 and LGG-2 pooled DNAs. P values calculated using Fisher's exact test and 2 × 2 contingency tables are shown. The level of significance (P < 0.05) is shown as a horizontal broken line.
Figure 2
Figure 2
In vitro radiosensitivity assay on human skin fibroblast cells treated with SEMA3A gene-directed siRNA. The relative clonogenic survival rate of cells at the indicated X-ray dose (Gy) is plotted. Open box: mock control. Closed triangle: SEMA3A siRNA1. Closed circle: SEMA3A siRNA2. The linear-quadratic model [27] of cell survival as a function of irradiated dose was fitted to the data. The asterisk indicates significant difference between the siRNA transfected cells and the control cells (P value < 0.05).
See this image and copyright information in PMC

References

    1. Bentzen SM, Overgaard J. Patient-to-patient variability in the expression of radiation-induced normal tissue injury. Semin Radiat Oncol. 1994;4:68–80. doi: 10.1016/S1053-4296(05)80034-7. - DOI - PubMed
    1. Iwakawa M, Noda S, Yamada S, Yamamoto N, Miyazawa Y, Yamazaki H, Kawakami Y, Matsui Y, Tsujii H, Mizoe J, Oda E, Fukunaga Y, Imai T. Analysis of non-genetic risk factors for adverse skin reactions to radiotherapy among 284 breast cancer patients. Breast Cancer. 2006;13:300–307. doi: 10.2325/jbcs.13.300. - DOI - PubMed
    1. Andreassen CN, Alsner J, Overgaard J. Does variability in normal tissue reactions after radiotherapy have a genetic basis - where and how to look for it? Radiother Oncol. 2002;64:131–140. doi: 10.1016/S0167-8140(02)00154-8. - DOI - PubMed
    1. Fernet M, Hall J. Genetic biomarkers of therapeutic radiation sensitivity. DNA Repair. 2004;3:1237–1243. doi: 10.1016/j.dnarep.2004.03.019. - DOI - PubMed
    1. Gatti RA. The inherited basis of human radiosensitivity. Acta Oncol. 2001;40:702–711. doi: 10.1080/02841860152619115. - DOI - PubMed

LinkOut - more resources