Abstract
ObjectiveTo study the relationship between DNA double-strand break (DSB) repair gene mutations and the risk of papillary thyroid microcarcinoma (PTMC).MethodsOne hundred patients with PTMC or benign thyroid nodules (BTNs) at Henan Cancer Hospital were retrospectively analyzed. The DSB repair capacity of peripheral blood T lymphocytes in the two groups was assessed by flow cytometry. Data were compared using Student’s t-test to evaluate the relationship between DSB repair capacity and the risk of PTMC. Factors influencing DSB repair capacity were analyzed by multivariate logistic regression analysis. The relationship between PTMC and DSB repair capacity was analyzed by univariate analysis. Targeted next-generation DNA sequencing was applied to screen and analyze DSB repair genes related to PTMC.ResultsThe DSB repair capacity was 31.30% in the PTMC group and 44.40% in the BTN group, with that of the former being significantly lower (P < 0.05). Multivariate logistic regression analysis of age, sex, obesity status, radiation and other factors showed that radiation exposure was positively correlated with reduced DSB repair capacity(OR = 3.642; 95% CI 1.484–8.935, P = 0.020). Moreover, univariate analysis showed that a reduction in DSB repair capacity was a risk factor for PTMC(OR = 2.333; 95% CI 1.027–5.300, P = 0.043).Targeted next-generation DNA sequencing was performed on the DSB repair genes discovered, and those that were mutated in association with PTMC were Rad50 and FANCA; Rad51 mutations were related to BTN.ConclusionRadiation exposure is positively associated with induced DSB repair gene mutations, which may cause a reduced capacity for DSB repair and eventually lead to PTMC.
Highlights
The incidence of thyroid cancer has increased in recent years, and it is currently the most common endocrine malignancy
In summary, this study focused on the role of double-strand break (DSB) repair gene mutations in thyroid carcinogenesis and explored risk factors that reduce DSB repair capacity
The results showed that patients with low DSB repair capacity have a significantly increased risk of papillary thyroid microcarcinoma (PTMC)
Summary
The incidence of thyroid cancer has increased in recent years, and it is currently the most common endocrine malignancy. Qin et al Cancer Cell Int (2021) 21:334 especially in children under 3 years old. There is a significant relationship between radiation and thyroid cancer in children [7]. Abdelaal [8] found that head leakage is an important factor of off-site dose in radiotherapy, especially in head and neck radiotherapy, with harmful effects on healthy tissues around the tumor and leading to the risk of secondary cancer. The gene repair process is initiated to address DNA damage, and radiation is the most common exogenous factor causing such damage, which can destroy the integrity of the genome. Radiation-induced genomic incompleteness may reduce DSB repair capacity, genetic instability and subsequent cancer [10], though the mechanism of reduced DSB repair capacity remains unclear.
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