Association of polymorphisms in genes of the homologous recombination DNA repair pathway and thyroid cancer risk.
BACKGROUND
Ionizing radiation exposure has been pointed out as a risk factor for thyroid cancer. The double-strand breaks induced by this carcinogen are usually repaired by homologous recombination repair pathway, a pathway that includes several polymorphic genes. Since there is a scarcity of data about the involvement of these gene polymorphisms in thyroid cancer susceptibility, we carried out a case-control study in a Caucasian Portuguese population.


METHODS
We genotyped 109 patients and 217 controls for the XRCC3 T241M, XRCC2 R188H, NBS1 E185Q, and RAD51 Ex1-59G>T polymorphisms to evaluate their potential main effects on risk for this pathology.


RESULTS
The results obtained showed that for the RAD51 Ex1-59G>T polymorphism, the homozigosity for the variant allele was associated with an almost significant increase of the odds ratio (OR) (adjusted OR = 1.9; confidence interval 95%: 1.0-3.5; p = 0.057). Additionaly, when the XRCC3 T241M data were analyzed concerning the presence of at least one wild-type allele, we observed that individuals homozygous for the variant allele had a higher risk for thyroid cancer (adjusted OR = 2.0; confidence interval 95%: 1.1-3.6; p = 0.026). When the data were analyzed according to the number of RAD51 Ex1-59G>T and XRCC3 T241M variant alleles, the coexistence of three or more variant alleles in either gene was associated to a significant higher risk (three variant alleles: adjusted OR = 2.9, p = 0.036; four variant alleles: adjusted OR = 8.0, p = 0.006).


CONCLUSIONS
Since XRCC3 is involved in the assembly and stabilization of RAD51 protein multimers at double-strand break sites, we cannot exclude that the interaction of both polymorphisms can lead to a decreased DNA repair capacity and consequently increased risk for thyroid cancer.
Bastos
Helder Novais
HN
Department of Genetics, Faculty of Medical Sciences, New University of Lisbon, P-1349-008 Lisbon, Portugal.
Antão
Mónica Rego
MR
Silva
Susana N
SN
Azevedo
Ana Paula
AP
Manita
Isabel
I
Teixeira
Valdemar
V
Pina
Julieta Esperança
JE
Gil
Octávia Monteiro
OM
Ferreira
Teresa Cruz
TC
Limbert
Edward
E
Rueff
José
J
Gaspar
Jorge Francisco
JF
D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D004260:DNA Repair / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011174:Portugal / Q000453:epidemiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D015398:Signal Transduction / Q000235:genetics; D012907:Smoking / Q000453:epidemiology; D013964:Thyroid Neoplasms / Q000453:epidemiology* / Q000235:genetics*
D004273:DNA, Neoplasm