0
Correspondence |

Intronic Boundary Mutation rs430397 Cannot Affect Alternate Splicing and Is an Indecisive Risk Factor for Non-small Cell Lung Cancerrs430397 and Non-Small Cell Lung Cancer Risk FREE TO VIEW

Xiao Zhu, PhD; Wenguo Fan, MD; Dongpei Li, MD
Author and Funding Information

From the Guangdong Provincial Key Laboratory of Medical Molecular Diagnosis (Dr Zhu), Guangdong Medical College; Cancer Institute and Affiliated Tumor Hospital (Dr Zhu), Guangzhou Medical University; and Department of Oral Anatomy and Physiology (Dr Fan), Guanghua School of Stomatology, and Zhongshan School of Medicine (Drs Fan and Li), Sun Yat-sen University.

Correspondence to: Dongpei Li, MD, Zhongshan School of Medicine, Sun Yat-sen University, No 74, Zhongshan 2 Rd, Guangzhou, 510080, China; e-mail: lidp@mail.sysu.edu.cn


Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Funding/Support: This work was supported by National Natural Science Foundation of China [Grant 81071697]; Research Project of Science and Information Technology of Guangzhou City [Grant 12C22061657]; Science and Technological Program for Dongguan’s Higher Education, Science and Research, and Health Care Institutions (to Dr Zhu); Natural Science Foundation of Guangdong Province [Grant S2011040003694]; Research Project of Education Bureau of Guangzhou City grant 10A192; and Research Project of Health Bureau of Guangzhou City [Grants 201102A213005 and 2010A30].

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2012;142(6):1691-1692. doi:10.1378/chest.12-1513
Text Size: A A A
Published online
To the Editor:

We thank Dr Merrick1 for his editorial comments on our article2 in CHEST (June 2012) on an intronic polymorphism (rs430397) in the glucose-regulated protein 78 (GRP78) gene and pharmacogenomics in non-small cell lung cancer (NSCLC) treated with platinum-based therapy. Alternative splicing is an important mechanism for gene expression, expanding the coding capacity of a single gene to allow production of different protein isoforms, which can have very different functions. For validating the hypothesis that intron/exon boundary polymorphism rs430397 affects alternative splicing, we performed resequencing of cDNA polymerase chain reaction products with forward primer AAAAGAAGACGGGCAAAG and reverse primer AGCCACCAACAAGAACAA. The latter is also the sequencing primer. In 60 blood samples of healthy control subjects, 45 hepatocellular carcinoma samples, and 66 NSCLC samples, we have not found evidence of functional splicing. Nonetheless, we still agree with Dr Merrick’s opinion that it will be of significant importance to study the impact of the rs430397 variant on protein localization, isoform generation, cell function, and so forth.

Again, this variant is also associated with hepatocellular carcinoma risk and prognosis.3 As a stress-inducible endoplasmic reticulum calcium-binding chaperone, GRP78 is used extensively as a biologic marker for onset of the unfolded protein response as well as a unique model for deciphering the mechanisms whereby endoplasmic reticulum stress upregulates nuclear gene expression.4 Here, we studied the possible association of rs430397 and NSCLC risk in China. An association analysis was carried out in the samples described.2,3 This study was approved by the ethics committee of Sun Yat-sen University. Additionally, all participants (or their guardians when necessary) provided written informed consent. The genotype-specific risks were estimated as ORs with associated 95% CIs using Pearson χ2 test. A trend test of ORs was used to assess an allele dose-dependent effect. As shown in Table 1, genotypes GG, AG, and AA are not associated with NSCLC risk, but the distribution trend of genotype shows some significance (Ptrend = .035). These data show that rs430397 is still not a risk factor of NSCLC. In addition to our previous results,3,5 we infer that intronic rs430397 mutation is still a controversial and indecisive contributing factor during the occurrence of disease stress.

Table Graphic Jump Location
Table 1 —Genotype Frequencies of rs430397 Among Patients With NSCLC and Control Patients and Trend Test

Data are presented as No. (%), unless otherwise indicated. NSCLC = non-small cell lung cancer.

Acknowledgments

Role of sponsors: The sponsors had no role in the design of the study, the collection and analysis of the data, the preparation of the manuscript, or in the decision to submit the article for publication.

Merrick DT. GRP78, intronic polymorphisms, and pharmacogenomics in non-small cell lung cancer. Chest. 2012;141(6):1377-1378. [CrossRef] [PubMed]
 
Zhu X, Lin MCM, Fan W, et al. An intronic polymorphism inGRP78improves chemotherapeutic prediction in non-small cell lung cancer. Chest. 2012;141(6):1466-1472. [CrossRef] [PubMed]
 
Zhu X, Chen MS, Tian LW, et al. Single nucleotide polymorphism of rs430397 in the fifth intron ofGRP78gene and clinical relevance of primary hepatocellular carcinoma in Han Chinese: risk and prognosis. Int J Cancer. 2009;125(6):1352-1357. [CrossRef] [PubMed]
 
Pfaffenbach KT, Lee AS. The critical role ofGRP78in physiologic and pathologic stress. Curr Opin Cell Biol. 2011;23(2):150-156. [CrossRef] [PubMed]
 
Zhu X, Chen L, Fan W, et al. An intronic variant in theGRP78, a stress-associated gene, improves prediction for liver cirrhosis in persistent HBV carriers. PLoS ONE. 2011;6(7):e21997. [CrossRef] [PubMed]
 

Figures

Tables

Table Graphic Jump Location
Table 1 —Genotype Frequencies of rs430397 Among Patients With NSCLC and Control Patients and Trend Test

Data are presented as No. (%), unless otherwise indicated. NSCLC = non-small cell lung cancer.

References

Merrick DT. GRP78, intronic polymorphisms, and pharmacogenomics in non-small cell lung cancer. Chest. 2012;141(6):1377-1378. [CrossRef] [PubMed]
 
Zhu X, Lin MCM, Fan W, et al. An intronic polymorphism inGRP78improves chemotherapeutic prediction in non-small cell lung cancer. Chest. 2012;141(6):1466-1472. [CrossRef] [PubMed]
 
Zhu X, Chen MS, Tian LW, et al. Single nucleotide polymorphism of rs430397 in the fifth intron ofGRP78gene and clinical relevance of primary hepatocellular carcinoma in Han Chinese: risk and prognosis. Int J Cancer. 2009;125(6):1352-1357. [CrossRef] [PubMed]
 
Pfaffenbach KT, Lee AS. The critical role ofGRP78in physiologic and pathologic stress. Curr Opin Cell Biol. 2011;23(2):150-156. [CrossRef] [PubMed]
 
Zhu X, Chen L, Fan W, et al. An intronic variant in theGRP78, a stress-associated gene, improves prediction for liver cirrhosis in persistent HBV carriers. PLoS ONE. 2011;6(7):e21997. [CrossRef] [PubMed]
 
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543