Radiation exposure, young age, and female gender are associated with high prevalence of RET/PTC1 and RET/PTC3 in papillary thyroid cancer: a meta-analysis

BACKGROUND RET/PTC rearrangements have been identified as a specific genetic event in papillary thyroid cancer (PTC). We conducted this meta-analysis to identify an enriched population who were more likely to occur RET/PTC fusion genes. METHODS All relevant studies in the PubMed, Web of Science, and Embase databases were searched up to June 2015. The studies found were screened according to our inclusion and exclusion criteria. All analyses were performed using STATA software. RESULTS Eventually, 38 eligible studies comprising 2395 participants were included. Overall analysis indicated that radiation exposure contributed to increased RET/PTC risk (OR = 2.82; 95%CI: 1.38-5.78, P = 0.005). Stratified analysis according to RET/PTC subtype and geographical area showed that this association was restricted to the RET/PTC3 subtype (OR = 8.30, 95%CI: 4.32-15.96, P < 0.001) in the Western population. In addition, age < 18 years, i.e., young age, was associated with higher prevalence of RET/PTC3 (OR = 2.03, 95%CI: 1.14-3.62, P = 0.017), especially in the radiation-exposure subpopulation (OR = 2.35, 95%CI: 1.01-5.49, P = 0.048). The association between female gender and RET/PTC1 risk was more significant in the PTC patients without radiation exposure (OR = 1.69, 95%CI: 1.04-2.74, P = 0.034). CONCLUSION Both radiation exposure and young age are associated with increased risk of RET/PTC3 and that female gender is associated with higher prevalence of RET/PTC1 in the subpopulation without radiation exposure. The RET/PTC status in combination with radiation exposure, age, and sex should be considered in the differential diagnosis of suspicious PTC.