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.
Highlights
Lung cancer is the most frequent solid tumor and the leading cause of cancer-related deaths in both developing and developed countries, which is a major public health problem worldwide [1, 2]
Since the genetic characteristics has been proved to contribute to lung cancer development, many molecular epidemiological studies have been conducted to evaluate the relationship between lung cancers and the genetic variety, such as single nucleotide polymorphisms (SNP) in genes which may be involved in lung cancer development
It has been proved that polymorphisms of DNA repair genes, such as the polymorphisms of XPA -4G>A, ERCC2 862G>A [12], MSH3 3133G>A, and PMS1 639G>A [13], are associated with the risk of lung cancer
Summary
Lung cancer is the most frequent solid tumor and the leading cause of cancer-related deaths in both developing and developed countries, which is a major public health problem worldwide [1, 2]. RRM1 Polymorphisms and Lung Cancer Susceptibility and 31%, respectively) than that at advanced stage (III/ IV) [3]. To identify certain population who may have susceptibility to lung cancer and diagnose lung cancer in early stage are crucial to improve treatment outcome. Since the genetic characteristics has been proved to contribute to lung cancer development, many molecular epidemiological studies have been conducted to evaluate the relationship between lung cancers and the genetic variety, such as single nucleotide polymorphisms (SNP) in genes which may be involved in lung cancer development. The DNA repair system plays an important role in protecting against mutagenesis and carcinogenesis. These genes are mainly involved in DNA maintenance and repair, carcinogen metabolism, cell cycle regulation, apoptosis, and so on. Some of the SNPs have been consistently shown to correlate with lung cancer susceptibility, including XPD [4], APEX, XRCC [5], POLG2, RECQL4 [6], and so on
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