Exonuclease 1 (EXO1) gene variation and melanoma risk.
OBJECTIVE
DNA repair pathway genes play an important role in maintaining genomic integrity and protecting against cancer development. This study aimed to identify novel SNPs in the DNA repair-related genes associated with melanoma risk from a genome-wide association study (GWAS).


METHODS
A total of 8422 SNPs from the 165 DNA repair-related genes were extracted from a GWAS of melanoma risk, including 494 cases and 5628 controls from the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). We further replicated the top SNPs in a GWAS of melanoma risk from the MD Anderson Cancer Center (1804 cases and 1026 controls).


RESULTS
A total of 3 SNPs with P value <0.001 were selected for in silico replication. One SNP was replicated: rs3902093 [A] in EXO1 promoter region (P(discovery)=6.6 × 10⁻⁴, P(replication)=0.039, P(joint)=2.5 × 10⁻⁴; OR(joint)=0.80, 95% CI: 0.71, 0.90). This SNP was associated with the expression of the EXO1; carriers of the A allele showed lower expression (P=0.002).


CONCLUSIONS
Our study found that a promoter region SNP in the editing and processing nucleases gene EXO1 was associated with decreased expression of EXO1 and decreased melanoma risk. Further studies are warranted to validate this association and to investigate the potential mechanisms.
Department of Epidemiology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
Fengju
F
Song
Abrar A
AA
Qureshi
Jiangwen
J
Zhang
Jiangwen
J
Zhan
Christopher I
CI
Amos
Jeffrey E
JE
Lee
Qingyi
Q
Wei
Jiali
J
Han
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D045643:DNA Repair Enzymes / Q000235:genetics*; D005090:Exodeoxyribonucleases / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008545:Melanoma / Q000201:enzymology* / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015203:Reproducibility of Results; D012307:Risk Factors
C114331:EXO1 protein, human; D005090:Exodeoxyribonucleases; D045643:DNA Repair Enzymes