Gender bias in individual radiosensitivity and the association with genetic polymorphic variations

Radiotherapy and Oncology 119 (2016) 236–243

Ghazi Alsbeih a,⇑, Rafa S. Al-Meer b, Najla Al-Harbi a, Sara Bin Judia a, Muneera Al-Buhairi a, Nikki Q. Venturina a, Belal Moftah c

a Radiation Biology Section, King Faisal Specialist Hospital and Research Centre; b Faculty of Science, King Saud University; and c Biomedical Physics Department, KFSHRC, Riyadh, Saudi Arabia 

Purpose: 

To assess the extent of variation in radiosensitivity between individuals, gender-related dissimilarity and impact on the association with single nucleotide polymorphisms (SNPs).

Materials and methods: 

Survival curves of 152 fibroblast cell strains derived from both gender were generated. Individual radiosensitivity was characterized by the surviving fraction at 2 Gy (SF2). SNPs in 10 radiation responsive genes were genotyped by direct sequencing.Results: 

The wide variation in SF2 (0.12–0.50; mean = 0.33) was significantly associated with 3 SNPs: TP53 G72C (P = 0.007), XRCC1 G399A (P = 0.002) and ATM G1853A (P = 0.01). Females and males differed significantly in radiosensitivity (P = 0.004) that impacted genetic association where only XRCC1 remained significant in both gender (P < 0.05). Meanwhile, discordant association was observed for TP53 that was significant in females (P = 0.012) and ATM that was significant in males (P = 0.0006). When gender-specific SF2-mean (0.31 and 0.35 for females and males; respectively) was considered, further discordance was observed where XRCC1 turned out not to be associated with radiosensitivity in males (P > 0.05).

Conclusions: 

Although the variation in individual radiosensitivity was associated with certain SNPs, gender bias for both endpoints was evident. Therefore, assessing the risk of radiation exposure in females and males should be considered separately in order to achieve the ultimate goal of personalized radiation medicine. 

Association between EGFR-TKI Resistance and Efficacy of Radiotherapy for Brain Metastases from EGFR-mutant Lung Adenocarcinoma

fuente: 

1. HIDENARI HIRATA¹, 
2. KATSUMASA NAKAMURA²⇑, 
3. NAONOBU KUNITAKE¹,
4. YOSHIYUKI SHIOYAMA³, 
5. TOMONARI SASAKI², 
6. SAIJI OHGA²,
7. TAKESHI NONOSHITA¹, 
8. TADAMASA YOSHITAKE³, 
9. KAORI ASAI²,
10. KOUJI INOUE⁴, 
11. AKIRA NAGASHIMA⁵, 
12. MINORU ONO¹ and
13. HIROSHI HONDA²

1. ¹Department of Radiology, Kitakyushu Municipal Medical Center, Kitakyushu, Japan
2. ²Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
3. ³Department of Heavy Particle Therapy and Radiation Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
4. ⁴Department of Respiratory Medicine, Kitakyushu Municipal Medical Center, Kitakyushu, Japan
5. ⁵Department of Respiratory Surgery, Kitakyushu Municipal Medical Center, Kitakyushu, Japan

Abstract

Aim: To clarify how patients with epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma with acquired resistance to EGFR-tyrosine kinase inhibitors (TKIs) respond to radiotherapy (RT) for brain metastases. Patients and Methods: Forty-seven patients were divided into the following three groups: a TKI-naïve group with EGFR mutation (n=11), a TKI-resistant group with EGFR mutation (n=10), and an EGFR-wild-type group (n=26). Patients received stereotactic RT (n=23) or whole-brain RT (n=24). Results: The response rate for patients with TKI-resistant tumor at three months after RT tended to be lower (11%) than that of those who were TKI-naïve (82%, p=0.006) and for patients with wild-type EGFR (48%, p=0.10). On univariate analysis, central nervous system progression-free and overall survival were significantly shorter for patients with TKI-resistant tumors than for those who were TKI-naïve (p=0.018 and p=0.005, respectively). Multivariate analysis showed that TKI resistance was an independent predictor of poorer overall survival (p=0.011). 

Conclusion: Acquired resistance to TKIs appears to be associated with low efficacy of brain RT.