domingo, 12 de junio de 2016

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. 

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