Association of DNA repair gene variants with colorectal cancer: risk, toxicity, and survival.
BACKGROUND
Single nucleotide polymorphisms (SNPs) in DNA repair genes have a potential clinical value in predicting treatment outcomes. In the current study, we examined the association of SNPs in the genes XRCC1-rs25487, ERCC1-rs11615, ERCC2-rs238406, and ERCC2-rs13181 with colorectal cancer (CRC) risk, relapse-free survival (RFS), overall survival (OS), and toxicity during chemotherapy.


METHODS
SNPs were analysed in 590 CRC cases and 300 controls using TaqMan technology. The association of SNPs with CRC risk and toxicity during chemotherapy was analysed using Chi2 test. The Kaplan-Meier method and log-rank test was used to measure the effects of the SNPs on RFS and OS.


RESULTS
The CC genotype of ERCC2-rs238406 and the ERCC2-rs13181 C allele were associated with a significantly increased risk of CRC. The ERCC1-rs11615 genotype T/T was associated with stomatitis in adjuvant chemotherapy (p = 0.03). Also, more patients with the ERCC2-rs13181 C allele needed dose reduction compared to patients with the A/A genotype (p = 0.02). In first line chemotherapy, more patients with the ERCC1-rs11615 C allele suffered from nausea compared to those with the T/T genotype (p = 0.04) and eye reactions and thrombocytopenia were more common in patients with the ERCC2-rs13181 C allele compared to the A/A genotype (p = 0.006 and p = 0.004, respectively). ERCC2- rs238406 C/C was also associated with a higher frequency of thrombocytopenia (p = 0.03). A shorter 5-year OS was detected in stage I & II CRC patients with the ERCC2- rs238406 C allele (p = 0.02). However, there was no significant association between the SNPs and 5-year RFS.


CONCLUSIONS
Both SNPs in ERCC2 were associated with risk of CRC as well as toxicity during first line treatment. In addition, ERCC2- rs238406 was linked to OS in early stage CRC. The ERCC1-rs11615 variant was associated with toxicity during adjuvant chemotherapy. The results add support to previous findings that SNPs in ERCC1 and ERCC2 have a prognostic and predictive value in clinical management of CRC.
['Salimzadeh|Hamideh|H|', 'Lindskog|Elinor Bexe|EB|', 'Gustavsson|Bengt|B|', 'Wettergren|Yvonne|Y|', 'Ljungman|David|D|http://orcid.org/0000-0003-0419-1118']
D000328:Adult D000368:Aged D000369:Aged, 80 and over D000971:Antineoplastic Combined Chemotherapy Protocols D017024:Chemotherapy, Adjuvant D015179:Colorectal Neoplasms D004268:DNA-Binding Proteins D064420:Drug-Related Side Effects and Adverse Reactions D004720:Endonucleases D005260:Female D005500:Follow-Up Studies D005838:Genotype D006801:Humans D008297:Male D008875:Middle Aged D009364:Neoplasm Recurrence, Local D020641:Polymorphism, Single Nucleotide D011379:Prognosis D012307:Risk Factors D015996:Survival Rate D000076105:X-ray Repair Cross Complementing Protein 1 D051759:Xeroderma Pigmentosum Group D Protein
Colorectal cancer Toxicity ERCC2 ERCC1 XRCC1