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. 

ASCO's New Guideline for Endocrine Therapy in Breast Cancer June 01, 2016

Key Recommendations for Women With HR-Positive Metastatic Breast Cancer
Hormone therapy should be offered to patients whose tumors express any level of estrogen and/or progesterone receptors, and treatment recommendations should be based on factors such as the type of adjuvant treatment being administered, disease-free interval, and the extent of disease at the time of recurrence
Use of a specific agent can be repeated if recurrence happens more than 12 months after the last treatment
Endocrine therapy should be recommended as the initial treatment in this patient population, except in the case of immediate life-threatening disease or rapid disease recurrence during adjuvant endocrine therapy
The use of combination endocrine therapy and chemotherapy is not recommended
For first-line therapy
	Postmenopausal women should be offered aromatase inhibitors (AIs)
	Combination hormone therapy with a nonsteroidal AI and fulvestrant (Faslodex, AstraZeneca) 500 mg and with a loading-dose schedule can be offered to patients who have not previously used endocrine therapy
	Premenopausal women should be offered ovarian suppression or ablation and hormone therapy; current agents have only been studied in the postmenopausal population
For second-line therapy
	Sequential hormone therapy should be offered except for those with rapid progression and organ dysfunction
	If fulvestrant is given, a 500 mg dose should be used, and with a loading schedule
For targeted therapy
	Postmenopausal women can be offered a nonsteroidal AI and palbociclib (Ibrance, Pfizer)
	Exemestane (Aromasin, Pfizer) and everolimus (Afinitor, Novartis) can be offered to postmenopausal women who progressed with nonsteroidal AIs, either before or after treatment with fulvestrant
	Fulvestrant and palbociclib can be offered to patients who experienced progression with AIs, with or without prior chemotherapy
	Adding HER2-targeted therapy to first-line AIs should be offered to patients with HR-positive and HER2-positive disease if they are not candidates for chemotherapy
	Genomic or expression profiling should not be used at this time to select treatment for metastatic HR-positive breast cancer