The study of the relation of DNA repair pathway genes SNPs and the sensitivity to radiotherapy and chemotherapy of NSCLC

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Abstract

To analyze the relation between SNPs in DNA repair pathway-related genes and sensitivity of tumor radio-chemotherapy, 26 SNPs in 20 DNA repair genes were genotyped on 176 patients of NSCLC undertaking radio-chemotherapy treatment. In squamous cell carcinoma (SCC), as the rs2228000, rs2228001 (XPC), rs2273953 (TP73), rs2279744 (MDM2), rs2299939 (PTEN) and rs8178085, rs12334811 (DNA-PKcs) affected the sensitivity to chemotherapy, so did the rs8178085, rs12334811 to radiotherapy. Moreover rs344781, rs2273953 and rs12334811 were related with the survival time of SCC. In general, the “good” genotype GG (rs12334811) showed greater efficacy of radio-chemotherapy and MSF (24 months) on SCC. In adenocarcinoma, as the rs2699887 (PIK3), rs12334811 (DNA-PKcs) influenced the sensitivity to chemotherapy, so did the rs2299939, rs2735343 (PTEN) to radiotherapy. And rs402710, rs80270, rs2279744 and rs2909430 impacted the survival time of the adenocarcinoma patients. Both GG (rs2279744) and AG (rs2909430) showed a shorter survival time (MFS = 6). Additionally, some SNPs such as rs2228000, rs2228001 and rs344781 were found to regulate the expression of DNA repair pathway genes through eQTLs dataset analysis. These results indicate that SNPs in DNA repair pathway genes might regulate the expression and affect the DNA damage repair, and thereby impact the efficacy of radio-chemotherapy and the survival time of NSCLC.

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Annual report on status of cancer in China, 2010.

Wanqing Chen, Rongshou Zheng, Siwei Zhang … (2014)

Population-based cancer registration data in 2010 were collected, evaluated and analyzed by the National Central Cancer Registry (NCCR) of China. Cancer incident new cases and cancer deaths were estimated. There were 219 cancer registries submitted cancer incidence and death data in 2010. All data were checked and evaluated on basis of the criteria of data quality from NCCR. Total 145 registries' data were qualified and accepted for cancer statistics in 2010. Pooled data were stratified by urban/rural, area, sex, age group and cancer site. Cancer incident cases and deaths were estimated using age-specific rates and national population. The top ten common cancers in different groups, proportion and cumulative rate were also calculated. Chinese census in 2000 and Segi's population were used for age-standardized incidence/mortality rates. All 145 cancer registries (63 in urban and 82 in rural) covered a total of 158,403,248 population (92,433,739 in urban and 65,969,509 in rural areas). The estimates of new cancer incident cases and cancer deaths were 3,093,039 and 1,956,622 in 2010, respectively. The morphology verified cases (MV%) accounted for 67.11% and 2.99% of incident cases were identified through death certifications only (DCO%) with mortality to incidence ratio (M/I) of 0.61. The crude incidence rate was 235.23/100,000 (268.65/100,000 in males, 200.21/100,000 in females), age-standardized incidence rates by Chinese standard population (ASIRC, 2000) and by world standard population (ASIRW) were 184.58/100,000 and 181.49/100,000 with the cumulative incidence rate (0-74 years old) of 21.11%. The cancer incidence and ASIRC were 256.41/100,000 and 187.53/100,000 in urban areas whereas in rural areas, they were 213.71/100,000 and 181.10/100,000, respectively. The crude cancer mortality in China was 148.81/100,000 (186.37/100,000 in males and 109.42/100,000 in females), age-standardized incidence rates by Chinese standard population (ASMRC, 2000) and by world standard population (ASMRW) were 113.92/100,000 and 112.86/100,000, and the cumulative incidence rate (0-74 years old) was 12.78%. The cancer mortality and ASMRC were 156.14/100,000 and 109.21/100,000 in urban areas, whereas in rural areas, they were 141.35/100,000 and 119.00/100,000 respectively. Lung cancer, gastric cancer, colorectal cancer, liver cancer, esophageal cancer, pancreas cancer, encephaloma, lymphoma, female breast cancer and cervical cancer, were the most common cancers, accounting for 75% of all cancer cases in urban and rural areas. Lung cancer, gastric cancer, liver cancer, esophageal cancer, colorectal cancer, pancreatic cancer, breast cancer, encephaloma, leukemia and lymphoma accounted for 80% of all cancer deaths. The coverage of cancer registration population had a rapid increase and could reflect cancer burden in each area and population. As the basis of cancer control program, cancer registry plays an irreplaceable role in cancer epidemic surveillance, evaluation of cancer control programs and making anti-cancer strategy. China is facing serious cancer burden and prevention and control should be enhanced.

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D B Donner, Lindsey Mayo (2002)

Oncoproteins and tumor-suppressor proteins regulate cell growth and viability. Recent observations show that phosphoinositide 3-kinase (PtdIns 3-kinase)-Akt signaling promotes the phosphorylation and movement of the Mdm2 oncoprotein into the nucleus, where it downregulates the p53 tumor-suppressor protein. The PTEN tumor suppressor protein inhibits activation of Akt and this restricts Mdm2 to the cytoplasm. Restriction of Mdm2 to the cytoplasm promotes p53 function and thereby sustains the sensitivity of cancer cells to chemotherapy. p53 acutely induces Mdm2, providing damaged cells the opportunity for repair, but subsequently induces PTEN, favoring the death of mutated or irrevocably damaged cells. Thus, oncoproteins and tumor suppressor proteins are networked to promote normal cell function and eliminate mutated cells.

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Is Open Access

A cross-platform analysis of 14,177 expression quantitative trait loci derived from lymphoblastoid cell lines

Liming Liang, Nilesh Morar, Anna L. Dixon … (2013)

Gene expression levels can be an important link DNA between variation and phenotypic manifestations. Our previous map of global gene expression, based on ∼400K single nucleotide polymorphisms (SNPs) and 50K transcripts in 400 sib pairs from the MRCA family panel, has been widely used to interpret the results of genome-wide association studies (GWASs). Here, we more than double the size of our initial data set with expression data on 550 additional individuals from the MRCE family panel using the Illumina whole-genome expression array. We have used new statistical methods for dimension reduction to account for nongenetic effects in estimates of expression levels, and we have also included SNPs imputed from the 1000 Genomes Project. Our methods reduced false-discovery rates and increased the number of expression quantitative trait loci (eQTLs) mapped either locally or at a distance (i.e., in cis or trans ) from 1534 in the MRCA data set to 4452 (with <5% FDR). Imputation of 1000 Genomes SNPs further increased the number of eQTLs to 7302. Using the same methods and imputed SNPs in the newly acquired MRCE data set, we identified eQTLs for 9000 genes. The combined results identify strong local and distant effects for transcripts from 14,177 genes. Our eQTL database based on these results is freely available to help define the function of disease-associated variants.

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Author and article information

Journal

Journal ID (nlm-ta): Sci Rep

Journal ID (iso-abbrev): Sci Rep

Title: Scientific Reports

Publisher: Nature Publishing Group

ISSN (Electronic): 2045-2322

Publication date (Electronic): 01 June 2016

Publication date Collection: 2016

Volume: 6

Electronic Location Identifier: 26526

Affiliations

[1 ]School of Life Science and Technology, Harbin Institute of Technology , Heilongjiang, China

[2 ]Department of Radiotherapy, Affiliated Tumour Hospital of Harbin Medical University

[3 ]Genome Analysis Laboratory, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences , China

[4 ]Department of Radiotherapy, Beijing Miyun County Hospital.

Author notes

[a ] liyugene@ 123456hit.edu.cn

[*]

These authors contributed equally to this work.

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Publisher Item ID: srep26526

DOI: 10.1038/srep26526

PMC ID: 4887885

PubMed ID: 27246533

SO-VID: 74b6a8b7-b77f-4706-84d2-a48b65745fb0

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This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

The study of the relation of DNA repair pathway genes SNPs and the sensitivity to radiotherapy and chemotherapy of NSCLC

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Most cited references 52

Annual report on status of cancer in China, 2010.

The PTEN, Mdm2, p53 tumor suppressor-oncoprotein network.

A cross-platform analysis of 14,177 expression quantitative trait loci derived from lymphoblastoid cell lines

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