RRM1 *151A>T, RRM1 ‐756T>C, and RRM1 ‐585T>Gis associated with increased susceptibility of lung cancer in Chinese patients

Abstract

Ribonucleotide reductase M1 (RRM1) is a crucial gene in DNA repair. Recent studies have shown that RRM1 expression can be a powerful predictor of survival or chemotherapy sensitivity in patients presenting with carcinomas who are treated with adjuvant gemcitabine‐based chemotherapy including lung cancer. However, the relationship between the single nucleotide polymorphisms (SNP) of RRM1 and the susceptibility of lung cancer to chemotherapy has not been well addressed. We detected six tag SNPs of RRM1 genotypes in a cohort of 1007 patients with primary lung cancer and 1007 age‐ and sex‐matched population controls using SNaPshot detection technology. Logistic regression, odds ratios (OR), and 95% confidence intervals were calculated to estimate lung cancer risk associated with SNP genotypes and haplotypes, after adjusting for case–control matching factors. Compared with the T/T and A/T genotype of RRM1 *151A>T, the A/A genotype had an increased risk for overall lung cancer (adjusted OR, 1.33). Additionally, the T/T+T/C genotypes of RRM1 ‐756T>C were risk factors that increased the susceptibility to lung cancer (adjusted OR 1.54, as compared with the C/C genotype). While the T/T+G/T genotypes of RRM1 ‐585T>G behaved as protective factors to increase the susceptibility to lung cancer (adjusted OR 0.44, as compared with the C/C genotype). In summary, this is the first study to systematically identify the relationship between the polymorphisms of RRM1 and individual susceptibility to lung cancer. It is anticipated that the RRM1 *151A>T, RRM1 ‐756T>C, and RRM1 ‐585T>G polymorphisms will improve the predictive prognosis of lung cancer sensitivity.

LINC02535 co‐functions with PCBP2 to regulate DNA damage repair in cervical cancer by stabilizing RRM1 mRNA

“…We discovered that there was a potential binding site between PCBP2 and RRM1 through starBase website. Previous studies have proved the pivotal role of RRM1 in promoting DNA synthesis and repair (Mlak et al, 2018;Toth et al, 2017;Xu, Zheng, Mao, & Ling, 2016), thus we hypothesized that LINC02535 and PCBP2 might have boosting effects on RRM1, therefore promoting DNA synthesis and repair. RIP assay indicated that RRM1 mRNA was abundantly enriched in anti-PCBP2 group compared with anti-IgG group (Figure 5a).…”

Gene‐Gene Interactions of Gemcitabine Metabolizing‐Enzyme Genes hCNT3 and WEE1 for Preventing Severe Gemcitabine‐Induced Hematological Toxicity

“…RRM1 is the molecular target of gemcitabine, and its mRNA expression is related to the efficacy of gemcitabine therapy 33 . Xu et al found that the T/T+T/C genotypes of RRM1 rs11030918 increased susceptibility to lung cancer 34 . However, to date, the relationship between RRM1 rs11030918 and gemcitabine‐induced hematological toxicities has not been well addressed.…”

WGS-based telomere length analysis in Dutch family trios implicates stronger maternal inheritance and a role for RRM1 gene

“…It is also targeted by certain chemotherapeutics or used as a biomarker to predict their effectiveness 44–46 . Furthermore, polymorphisms and altered expression of this gene have been linked to increased susceptibility to certain cancers 45,47 . RRM1 ’s role in cancer, however, is only discussed in terms of its involvement in DNA synthesis, and not in terms of telomere length regulation.…”