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Table 1 The radiosensitivity level of breast cancer patients, BRCA1/2 mutation carriers and breast cancer patients with radiotherapy complication, using micronucleus assay

From: Molecular contribution of BRCA1 and BRCA2 to genome instability in breast cancer patients: review of radiosensitivity assays

Reference

Marker

Sample size

Cell type

Radiation dose

Result

Breast cancer

 Francies et al. 2019 [132]

G2 MN assay

1. BC cases (34)

A. TNBC (17)

B. Luminal (17)

2. Healthy controls (17)

Lymphocyte

2 and 4 Gy

X-rays

Spontaneous RS

TNBC ↔ Healthy controls

Luminal ↔ Healthy controls

RS after radiation

2-Gy X-rays

TNBC ↔ Healthy controls

Luminal ↔ Healthy controls

4-Gy X-rays

TNBC ↔ Healthy controls

Luminal > Healthy controls

 Francies et al. 2019 [132]

G0 MN assay

1. BC cases (83)

A. TNBC (17)

B. Luminal (66)

2. Healthy controls (90)

Lymphocyte

2 and 4 Gy

X-rays

Spontaneous RS

BC cases > Healthy controls

TNBC > Healthy controls

Luminal > Healthy controls

RS after radiation

2-Gy X-rays

BC cases > Healthy controls

TNBC ↔ Healthy controls

Luminal > Healthy controls

4-Gy X-rays

BC cases > Healthy controls

TNBC ↔ Healthy controls

Luminal > Healthy controls

 Lou et al. 2008 [133]

G0 MN assay

1. BC cases (25)

2. Healthy controls (25)

Lymphocyte

3-Gy

X-rays

Spontaneous RS

BC case > Healthy controls

RS after radiation

BC case > Healthy controls

 Djuzenova et al. 2006 [12]

G2 MN assay

1. BC cases (50)

2. Healthy controls (16)

PBMC

1, 2, 3 and 4 Gy

X-rays

Spontaneous RS

BC cases ↔ Healthy controls

Slope of MN induction

BC cases ↔ Healthy controls

 Varga et al (2007) [11]

G0 MN assay

1. BC cases (91)

2. Healthy controls (96)

Lymphocyte

2 Gy

γ-rays

Spontaneous RS

BC cases > Healthy controls

RS after radiation

BC cases > Healthy controls

 Mozdarani et al. 2005 [5]

G0 MN assay

1. BC cases (50)

2. Healthy controls (40)

Lymphocyte

3 Gy

γ-rays

Spontaneous RS

BC cases > Healthy controls

RS after radiation

BC cases > Healthy controls

 Ban et al. 2004 [10]

G0 MN assay

1. BC cases (130)

2. Healthy controls (48).

Lymphocyte

2 Gy

X-rays

Spontaneous RS

BC cases > Healthy controls

RS after radiation

BC cases > Healthy controls

 Barber et al. (2000) [134]

G2 MN assay

1. BC cases (11)

2. First degree relative of BC cases (22)

2. Healthy controls (68)

Lymphocyte

3.5 Gy

γ-rays

Spontaneous RS

BC cases > Healthy controls

Relative of BC cases > Healthy controls

 Scott et al. 1999 [135]

G0 MN assay

1. BC cases (130)

2. Healthy controls (68)

Lymphocyte

3.5 Gy

γ-rays

Spontaneous RS

BC cases ↔ Healthy controls

RS after radiation

BC cases > Healthy controls

 Scott et al. 1998 [136]

G0 MN assay

1. BC cases (39)

2. Healthy controls (42)

Lymphocyte

HDR

3.5 Gy γ-rays

(dose rate 1.0 Gy min-1)

LDR

3.5 Gy γ-rays

(dose rate 0.15 Gy min-1)

Spontaneous RS

BC cases > Healthy controls

HDR

RS after radiation

BC cases > Healthy controls

LDR

RS after radiation

BC cases > Healthy controls

BRCA1/2 mutation

 Baert et al. 2017 [137]

G2 MN assay

1. Healthy BRCA2 mutation carriers (18)

2. Non-carrier subjects from BRCA1/2 families (17)

3. Healthy controls W/O family history of BC (18)

Lymphocyte

2 Gy

γ-rays

Spontaneous RS

No difference across all groups

RS after radiation

Healthy BRCA2 mutation carrier > Healthy controls

Healthy BRCA2 mutation carrier ↔

Non-carrier subjects from BRCA1/2 families

 Baert et al. 2016 [130]

G2 MN assay

1. Healthy BRCA1 mutations carriers (18)

2. Healthy controls W/O family history of BC (20)

Lymphocyte

2 Gy

γ-rays

Spontaneous RS

Healthy BRCA1 mutation carriers ↔ Healthy controls

RS after radiation

Healthy BRCA1 mutation carriers > Healthy controls

 Gutierrez-Enriquez et al. 2011 [138]

G2 MN assay

1. 21 BRCA1 carriers (12 BC and 9 Healthy)

2. 24 BRCA2 carriers (13 BC and 11 Healthy)

3. Familial BC cases W/O BRCA1/2 mutation (15)

4. 16 healthy controls W/O

familial history of BC (5 BC and 11 Healthy)

Lymphocyte

Mitomycin C

RS after radiation

BRCA1 carriers ↔ Healthy controls

BRCA2 carriers > Healthy controls

BRCA2 carriers > BRCA1 carriers

 Kotsopoulos et al. 2007 [13]

G2 MN assay

1. Healthy BRCA1 mutation carriers (25)

2. Non-carrier subjects from BRCA1 families (25)

Lymphocyte

2 Gy

γ-rays

Spontaneous RS

Healthy BRCA1 mutation carriers ↔ Non-carrier subjects

RS after radiation

Healthy BRCA1 mutation carriers ↔ Non-carrier subjects

 Varga et al (2007) [11]

G0 MN assay

1. BC cases (85)

2. BC cases with BRCA1 mutation (6)

3. Healthy controls (96)

Lymphocyte

2 Gy

γ-rays

Spontaneous RS

BC with BRCA1 mutation ↔ Healthy controls

RS after radiation

BC with BRCA1 mutation > Healthy controls

 Baeyens et al (2002) [139]

G0 MN assay

1. BC cases with BRCA1/2 mutation (20)

A. BRCA1(11)

B. BRCA2 (9)

2. Healthy relative with BRCA mutation (12)

A. BRCA1 (6)

B. BRCA2 (6)

3. Healthy relative W/O BRCA mutation (10)

A. of BRCA1 (5)

B. of BRCA2 (5)

4. BC cases W/O BRCA mutation (78)

5. Healthy controls (58)

Lymphocyte

HDR

2 Gy γ-rays and

3.5 Gy γ-rays

(dose rate 1.0 Gy min-1)

LDR

3.5 Gy γ-rays

(dose rate 4 mGy min-1)

Spontaneous RS

BC cases > Healthy controls

BC with BRCA1/2 mutation ↔ BC W/O BRCA1/2 mutation

Healthy relative with and W/O BRCA1/2 mutation ↔ Healthy controls

HDR & LDR

RS after radiation

BC with BRCA1/2 mutation > Healthy controls

BC with BRCA1/2 mutation ↔ BC W/O BRCA1/2 mutation

Healthy relative with BRCA1/2 mutation ↔ Healthy relative W/O BRCA1/2 mutation ↔ Healthy controls

 Trenz et al (2003) [140]

G2 MN assay

1. Healthy BRCA1 mutation carrier (13)

2. Healthy controls W/O familial history of cancer (13)

Lymphocyte

2 Gy

γ-rays

Spontaneous RS

Healthy BRCA1 mutation carriers ↔ Healthy controls

RS after radiation

Healthy BRCA1 mutation carriers > Healthy controls

 Trenz et al (2002) [141]

G2 MN assay

1. Healthy BRCA1 mutation carrier (10)

2. Healthy BRCA2 mutation carrier (9)

3. Healthy controls W/O familial history of cancer (14)

Lymphocyte

2 Gy

γ-rays

Spontaneous RS

Healthy BRCA1 mutation carriers ↔ BRCA2 mutation carriers

RS after radiation

Healthy BRCA1 mutation carriers ↔ BRCA2 mutation carriers

Healthy BRCA1 mutation carriers > Healthy controls

Healthy BRCA2 mutation carriers > Healthy controls

 Rothfus et al. (2000) [142]

G2 MN assay

1. Healthy BRCA1 mutation carriers (12)

2. Non-carrier subjects from BRCA1 families (10)

3. Healthy controls W/O history of cancer (17)

Lymphocyte

2 Gy

γ-rays

RS after radiation

Healthy BRCA1 mutation carriers> Non-carrier subjects from BRCA1 families

Non-carrier subjects from BRCA1 families ↔ Healthy controls

Radiotherapy complications

 Finnon et al. 2012 [143]

G0 MN assay

1. BC cases with ASR (31)

2. BC cases with mild late adverse reaction (28)

PBMC

3.5 Gy

X-rays

RS after radiation

Marked reaction ↔ Mild late adverse reaction

 Djuzenova et al. 2006 [12]

G2 MN assay

1. BC cases with ASR (9)

2. BC cases (50)

3. Healthy controls (16)

PBMC

1, 2, 3 and 4 Gy

X-rays

Spontaneous RS

BC with ASR > Healthy controls

BC with ASR > BC cases

Slope of MN induction

BC with ASR > Healthy controls

BC with ASR > BC cases

 Taghavi-Dehaghani et al. 2005 [144]

G0 MN assay

BC cases with early reactions (15)

BC cases with late reactions (11)

Lymphocyte

4 Gy

γ-rays

Spontaneous RS

Early reactions ↔ Late reactions

RS after radiation

Early reactions > Late reactions

 Barber et al. 2000 [134]

G0 MN assay

HDR

ASR before radiotherapy (116)

Late reactions, 8-14 years after radiotherapy (47)

LDR

ASR before radiotherapy (73)

Late reactions, 8-14 years after radiotherapy (26)

Lymphocyte

HDR

3.5 Gy γ-rays

(dose rate 1.0 Gy min-1)

LDR

3.5 Gy γ-rays

(dose rate 0.15 Gy min-1)

HDR

RS after radiation

Acute reactions before radiotherapy ↔ 8-14 years after radiotherapy

LDR

RS after radiation

Acute reactions before radiotherapy ↔ 8-14 years after radiotherapy

  1. RS radiosensitivity, MN micronucleus, BC breast cancer, PBMC peripheral blood mononuclear cell, HDR high dose rate, LDR low dose rate, CBMN cytokinesis-block micronucleus, ASR adverse early skin reaction, TNBC triple negative breast cancer, W/O without, Gr: gray
  2. ↔: no significant differences at the radiosensitivity level, >: significant higher level of radiosensitivity