The role of common variants of non-homologous end-joining repair genes XRCC4, LIG4 and Ku80 in thyroid cancer risk.
Variations, such as single nucleotide polymorphisms (SNPs) in DNA damage repair genes have been pointed out as possible factors to cancer predisposition. Ionizing radiation (IR) induces DNA double strand breaks (DSBs) and is the main recognized risk factor for thyroid cancer. However, most of the patients do not show chronic contact with IR and the other factors have non-concordant data. Thus, thyroid cancer could be due to gene variations in association with certain exogenous factors. One of the pathways that repair DSBs is DNA non-homologous end-joining (NHEJ) that comprises several polymorphic genes. We intend to study the role of polymorphic variants in XRCC4, LIG4 and Ku80 genes, since there is scarcity of data on the role of these genes in thyroid cancer susceptibility. We carried out a hospital-based case-control study in a Caucasian Portuguese population (109 patients and 217 controls) to estimate the potential role of the XRCC4 (N298S and T134I), LIG4 (T9I) and Ku80 (Ex21-238Gright curved arrow A, Ex21+338Tright curved arrow C, Ex21-352Cright curved arrow A, Ex21+466Aright curved arrow G) polymorphisms in the individual susceptibility for this disease. The results here reported do not associate these polymorphisms with susceptibility for non-familial thyroid cancer. However, when the data were analyzed according to the type of tumour, significant results for Ku80 Ex21-238Gright curved arrow A and Ex21+466Aright curved arrow G were found for papillary tumours (adjusted OR = 2.281; 95% CI =; 1.063-4.894; P=0.034). Taken together these results suggest that some of these variants in NHEJ genes can contribute to thyroid cancer susceptibility. However, further studies with a larger sample size will be needed to support our results.
Gomes
Bruno Costa
BC
Department of Genetics, Faculty of Medical Sciences, Universidade Nova de Lisboa, 1349-008 Lisboa, Portugal.
Silva
Susana Nunes
SN
Azevedo
Ana Paula
AP
Manita
Isabel
I
Gil
Octávia Monteiro
OM
Ferreira
Teresa Cruz
TC
Limbert
Edward
E
Rueff
José
J
Gaspar
Jorge Francisco
JF
D000328:Adult; D000368:Aged; D034961:Antigens, Nuclear / Q000235:genetics*; D016022:Case-Control Studies; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D000072200:Ku Autoantigen; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D013964:Thyroid Neoplasms / Q000235:genetics*
D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; C000607893:LIG4 protein, human; C101467:XRCC4 protein, human; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen; D011088:DNA Ligases; D000072481:DNA Ligase ATP