Genetic variations in DNA repair genes, radiosensitivity to cancer and susceptibility to acute tissue reactions in radiotherapy-treated cancer patients

Figures & data

Figure 1.  Radiation exposure at low doses mostly results in DNA double strand breaks (DSBs), which are repaired through homologous recombination and non-homologous end joining. The last pathway is the major mechanism of the repair of DNA DSBs in humans and other mammals.

Table I.  Summary of case-control and functional studies for association of different variants of the XRCC3 gene with radiosensitivity

Marker	Population	Cancer	Type of radiotherapy (radiation-induced complications)	Cases	Controls	OR	p	Reference
Micro-satellite (AC)n intron 3	U.K. Caucasians	Mostly breast and ovarian	Chest, pelvis	106 radio-sensitive with cancer 137 cancer complicated with radiotherapy-induced acute reactions	215 cancer-free	N/A	0.004 (cancer vs. cancer-free) 0.005 (complicated vs. cancer)	[103]
T241M	US (North Carolina)	Family history of breast cancer	No	135 cancer-free women including 83 for whom family history of breast cancer was available		N/A	N.S. for prolonged cell cycle G2 delay N.S. for family history of cancer	[91]
T241M	U.S. (mostly Caucasians; North Carolina)	Breast	Chest	118 cancer females (83% Whites)	224 cancer-free females (83% Whites)	N/A	N.S. for breast cancer risk N.S. for prolonged cell cycle G2 delay	[92]
T241M	US (Texas)	No cancer	Irradiation of lymphocytes with x-rays	80 smoke-free and cancer-free donors		N/A	< 0.05 (MM + TM vs. TT) for number of radiation-induced chromosome deletions	[96]
T241M	Denmark	Breast	Chest (radiogenic subcutaneous fibrosis and telangiectasia)	41 females treated with post-mastectomy radiotherapy		Enhance-ment Ratio = 1.17 Enhance-ment Ratio = 1.25	<0.05 (TM vs. TT) for grade 3 subcutaneous fibrosis <0.05 (MM vs. TT) for grade 2-3 telangiectasia	[95]
T241M	Belgium	No cancer	γ-irradiation during work; γ-irradiation of blood cells taken from cases and controls	32 men (seasonal cleaners of the reactor of the Belgian nuclear power plant)	31 men (office staff of the Belgian nuclear power plant with no radiation exposure)	N/A	<0.012 (MM + MT vs. TT) for frequency of microniclei in monocytes of exposed workers	[97]
T241M	Israel	Meningioma	RT against tinea capitis in childhood (radiogenic meningioma)	150 with radiation-induced meningioma 69 with non-radiation-induced meningioma	129 irradiated but did not developed meningioma 92 non-irradiated without meningioma	1.18	N.S. (MM vs. TT) for risk of radiation-induced meningioma	[90]
T241M	UK	Breast	Chest	26 cancer with changes in breast appearance after radiotherapy	26 cancer with no changes in breast appearance after radiotherapy	N/A	N.S. (cases vs. controls) for risk of altered breast appearance after radiotherapy	[93]
T241M, 5′ UTR 4541A > G, IVS5-14 A > G	Belgium	Cervical and endometrial	Pelvis (late normal tissue reactions induced by RT)	62 (30 with cervical cancer and 32 with endometrial cancer) including 40 with visible reactions to radiotherapy and 22 with no reaction to raduiotherapy	150 cancer-free women	7.94 2.12 3.71 3.98 10.1	N.S. (for T241M) 5′ UTR 4541A > G: 0.019 for GG (cases vs. controls) 0.024 for GG + AG (cases vs. controls) IVS5-14 A > G: 0.046 for AG (cancer with visible RT reactions vs. cancer with no reactions) 0.025 for AG + GG (cancer with visible RT reactions vs. cancer with no reactions) 0.001 for GG (IVS5-14 A > G) + XRCC1 [194 R/W + 399 R/H + 692 Q/Q] (cancer with visible RT reactions vs. cancer with no reactions)	[94]
Micro-satellite (AC)n intron 3	Belgium	Cervical and endometrial	Pelvis	62 (30 with cervical cancer and 32 with endometrial cancer)	118 cancer-free females	2.56	0.055 (homozygotes for allele 16; cases vs. controls)	[104]
T241M	US (North Carolina): Whites and Blacks	Breast	Chest	1 417 Whites with cancer + 894 Blacks with cancer (both include 835 treated with radiotherapy to the chest	1 234 cancer-free Whites and 788 cancer-free Blacks	N/A	N.S. (cancer cases vs. controls) N.S. (RT-treated cases vs. non-irradiated cases)	[70]
5′ UTR 4541A > G, IVS5-14 A > G	Canada (mostly Caucasians)	Prostate	Brachytherapy (RT-induced bladder and rectal toxicity)	124 RT-treated including 83 who developed clinical late toxicity (of these 83, 28 developed grade ≥2 late bladder or rectal toxicity		Hazard Ratio = 4.83	5′ UTR 4541A > G: 0.004 for AA (risk of grade ≥2 chronic toxicity)	[38]
T241M	Germany	Breast	RT after breast conserving surgery (acute skin toxicity: moist desquamation)	446 RT-treated including 77 who exhibited acute skin toxicity		N/A	N.S. (cases with RT-induced skin toxicity vs. cases with no visible RT-related complications)	[71]
T241M	Denmark	Breast	Chest (radiogenic subcutaneous fibrosis)	120 RT-treated post-mastectomy females		N/A	N.S. (MM vs. TT) for risk of RT-induced subcutaneous fibrosis	[37]

Abbreviations: N/A, not available; OR, Odds Ratio; RT, radiotherapy; MM, MT, and TT, genotypes of the T241M XRCC3 gene.

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