Association between GWAS-Derived rs966423 Genetic Variant and Overall Mortality in Patients with Differentiated Thyroid Cancer
PBN-AR
Instytucja
Centrum Nowych Technologii UW (Uniwersytet Warszawski)
Informacje podstawowe
Główny język publikacji
en
Czasopismo
Clinical Cancer Research
ISSN
1078-0432
EISSN
Wydawca
AMER ASSOC CANCER RESEARCH
DOI
URL
Rok publikacji
2016
Numer zeszytu
5
Strony od-do
1111-1119
Numer tomu
22
Identyfikator DOI
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Autorzy
Pozostali autorzy
+ 8
Streszczenia
Język
en
Treść
Purpose: Five germline genetic variants (rs116909374, rs965513, rs944289, rs966423, and rs2439302) have been associated in genome-wide association studies (GWAS) with increased risk of differentiated thyroid cancer (DTC), but their role in mortality of patients has not been established. Also, no preoperative marker of the clinical outcome of thyroid cancer had yet been identified. The aim of the study was to investigate the relationship between the variants and overall mortality in patients with DTC.Experimental Design: Retrospective study of 1,836 patients (1,643 women, 193 men) with median age at diagnosis of 49 years and overall median follow-up time of 8.7 years after initial treatment at a single comprehensive cancer center between 1990 and 2013.Results: Among 5 variants, rs966423 was associated with increased mortality, which was 6.4% (33 of 518) versus 3.7% (47 of 1,259) in TT carriers versus CC/CT carriers (P = 0.017). The HR of TT versus TC/CC carriers was 1.6 [95% confidence interval (CI), 1.02–2.49; P = 0.038] after adjustment for age at diagnosis and sex. Importantly, the association of rs966423 with mortality remained valid when clinicopathologic risk factors were included in the model (HR, 1.89; 95% CI, 1.14–3.13; P = 0.014). Higher rs966423–associated patient mortality of TT versus CC/CT carriers was also observed in interaction with angioinvasion (adjusted HR, 3.48; 95% CI, 1.67–7.22; P < 0.001), lymph node metastasis (adjusted HR, 3.47; 95% CI, 1.16–10.4; P = 0.018), extrathyroidal invasion (adjusted HR, 2.07; 95% CI, 1.15–3.73; P = 0.013).Conclusions: The presence of the rs966423-TT genotype was associated with a significant increase in overall mortality of patients with DTC. Contrary to BRAF mutation and other somatic changes, the status of germline rs966423 is known before the treatment and might be used in the management of mortality risk by means of modification of therapy. Clin Cancer Res; 1–9. ©2015 AACR.
Cechy publikacji
ORIGINAL_ARTICLE
Inne
System-identifier
702077
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