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      Polymorphisms in the H19 gene and the risk of lung Cancer among female never smokers in Shenyang, China

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          Abstract

          Background

          Long non-coding RNA (lncRNA) H19 is a hot spot in tumor development, progression and metastasis. This study assessed the association between H19 genetic polymorphisms and the susceptibility of lung cancer.

          Methods

          The case-control study was conducted to evaluate the association between four selected single nucleotide polymorphisms (rs217727, rs2107425, rs2735469 and rs17658052) in H19 gene and the risk of lung cancer. There were 556 female never smoking lung cancer patients and 395 cancer-free controls. Unconditional logistic regression analysis was used to analyze the associations between four SNPs and lung cancer risks by calculating the odds ratios and their 95% confidence intervals. The gene-environment interactions were assessed on both additive and multiplicative scales.

          Results

          Compared with carriers carrying homozygous CC genotype, there was a statistically significant increased risk of lung cancer for carriers of the rs2107425 TT genotype (odds ratio = 1.599, 95%CI = 1.106–2.313, P = 0.013). In both dominant and recessive models, significant associations were found between rs2107425 and lung cancer risk, and the corresponding odds ratios were 1.346 (1.022–1.774) and 1.400 (1.011–1.937), with P values 0.035 and 0.043, respectively. There was no significant correlation between lung cancer risk and rs2735469, rs217727 and rs17658052. Interaction analysis showed that their combined effects had a greater impact on lung cancer than individual effects of polymorphism and cooking smoke exposure. However, further analysis showed that the both additive model and the multiplicative model were not statistically significant.

          Conclusion

          The polymorphism rs2107425 in H19 gene was associated with the risk of lung cancer among female who never smokes in Shenyang, China.

          Electronic supplementary material

          The online version of this article (10.1186/s12885-018-4795-6) contains supplementary material, which is available to authorized users.

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          Up-regulated long non-coding RNA H19 contributes to proliferation of gastric cancer cells.

          Feng Yang, Jianwei Bi, Xuchao Xue … (2012)
          Long non-coding RNAs (lncRNAs) have been shown to have important regulatory roles in cancer biology, and the lncRNA H19 is up-regulated in hypoxic stress and in some tumors. However, the contributions of H19 to gastric cancer remain largely unknown. In this study, we assayed the H19 expression level in gastric cancer tissues by real-time PCR, and defined the biological functions by flow cytometry and RNA immunoprecipitation. We demonstrated that H19 levels were markedly increased in gastric cancer cells and gastric cancer tissues compared with normal controls. Moreover, ectopic expression of H19 increased cell proliferation, whereas H19 siRNA treatment contributed to cell apoptosis in AGS cell line. We further verified that H19 was associated with p53, and that this association resulted in partial p53 inactivation. These data suggest an important role for H19 in the molecular etiology of gastric cancer and potential application of H19 in gastric cancer therapy. © 2012 The Authors Journal compilation © 2012 FEBS.
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            Estimates of the worldwide incidence of eighteen major cancers in 1985.

            P Pisani, J Ferlay, D Parkin (1993)
            The annual incidence rates (crude and age-standardized) and numbers of new cases of 18 different cancers have been estimated for the year 1985 in 24 areas of the world. The total number of new cancer cases (excluding non-melanoma skin cancer) was 7.6 million, 52% of which occur in developing countries. The most common cancer in the world today is lung cancer, accounting for 17.6% of cancers of men worldwide, and 22% of cancers in men in the developed countries. Stomach cancer is now second in frequency (it was slightly more common than lung cancer in 1980) and breast cancer--by far the most important cancer of women (19.1% of the total)--is third. There are very large differences in the relative importance of the different cancers by world area. The major cancers of developed countries (other than the 3 already named) are cancers of the colon-rectum and prostate, and, in developing countries, cancers of the cervix uteri, mouth and pharynx, liver and oesophagus. The implications of these patterns for cancer control, and specifically prevention, are discussed. Tobacco smoking and chewing are almost certainly the major preventable causes of cancer today.
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              Pancreatic cancer risk variant in LINC00673 creates a miR-1231 binding site and interferes with PTPN11 degradation.

              Jian Zheng, Xudong Huang, Wen-wen Tan … (2016)
              Genome-wide association studies have identified several loci associated with pancreatic cancer risk; however, the mechanisms by which genetic factors influence the development of sporadic pancreatic cancer remain largely unknown. Here, by using genome-wide association analysis and functional characterization, we identify a long intergenic noncoding RNA (lincRNA), LINC00673, as a potential tumor suppressor whose germline variation is associated with pancreatic cancer risk. LINC00673 is able to reinforce the interaction of PTPN11 with PRPF19, an E3 ubiquitin ligase, and promote PTPN11 degradation through ubiquitination, which causes diminished SRC-ERK oncogenic signaling and enhanced activation of the STAT1-dependent antitumor response. A G>A change at rs11655237 in exon 4 of LINC00673 creates a target site for miR-1231 binding, which diminishes the effect of LINC00673 in an allele-specific manner and thus confers susceptibility to tumorigenesis. These findings shed new light on the important role of LINC00673 in maintaining cell homeostasis and how its germline variation might confer susceptibility to pancreatic cancer.
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                Author and article information

                Contributors
                Zhihua Yin: zhyin@cmu.edu.cn
                Zhigang Cui: zgcui@cmu.edu.cn
                Hang Li: lihangatcmu@126.com
                Juan Li: 1196349613@qq.com
                Baosen Zhou: bszhou@cmu.edu.cn
                Journal
                Journal ID (nlm-ta): BMC Cancer
                Journal ID (iso-abbrev): BMC Cancer
                Title: BMC Cancer
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1471-2407
                Publication date (Electronic): 15 September 2018
                Publication date PMC-release: 15 September 2018
                Publication date Collection: 2018
                Volume: 18
                Electronic Location Identifier: 893
                Affiliations
                [1 ]ISNI 0000 0000 9678 1884, GRID grid.412449.e, Department of Epidemiology, , China Medical University, ; No. 77, Puhe Road, Shenyang North District, Shenyang, 110122 People’s Republic of China
                [2 ]ISNI 0000 0000 9678 1884, GRID grid.412449.e, School of Nursing, , China Medical University, ; Shenyang, 110122 People’s Republic of China
                Article
                Publisher ID: 4795
                DOI: 10.1186/s12885-018-4795-6
                PMC ID: 6139161
                PubMed ID: 30219045
                SO-VID: 7d27399a-b7b8-4be2-8aee-9eda50aa4a84
                Copyright © © The Author(s). 2018
                License:

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 30 October 2017
                Date accepted : 4 September 2018
                Funding
                Funded by: Program for Innovation Talents in Universities of Liaoning Province
                Award ID: LR2016026
                Award Recipient :
                Categories
                Subject: Research Article
                Custom metadata
                issue-copyright-statement © The Author(s) 2018

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: lung cancer,h19,single nucleotide polymorphism,cooking oil fume,interaction
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: lung cancer, h19, single nucleotide polymorphism, cooking oil fume, interaction

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