Introduction
Cancer is the second most common cause of death worldwide. Cancer was responsible for 8.8 million deaths in 2015. Almost 70% of cancer-related deaths occur in low- and middle-income countries (Siegel et al., 2015). Several lifestyle risk factors, including high body mass index, low fruit and vegetable intake, lack of physical activity, and tobacco and alcohol consumption, account for nearly one-third of deaths from cancer (Forouzanfar et al., 2016, Hoseini et al., 2014). The economic impact of cancer is substantial and increasing (McGuire, 2016).
Various factors, including environmental and genetic factors, are among the most common ones that contribute to cancer development. However, the mechanisms underlying cancer pathogenesis remain largely unclear. Long non-coding RNAs (lncRNAs) have been widely investigated among the potential genetic factors. It has been proposed that they play a crucial role in cancer progression, tumorigenesis, and the biological activity of malignant tumors (Kong et al., 2014, Hu et al., 2015, Hosseini et al., 2022). These single-stranded, non-coding RNAs are among the significant regulators of gene expression, including oncogenes and tumor suppressor genes, cell cycle, proliferation, differentiation, and apoptosis (Bartonicek et al., 2016, Zhang et al., 2016, Chen et al., 2012, Bhan and Mandal, 2014).
To date, several lncRNAs have been discovered in the human genome (Brosnan and Voinnet, 2009, Rashidmayvan et al., 2022). Genetic variants, specifically the single nucleotide polymorphisms (SNPs), located in lncRNA genes have the potential to make a crucial impact on lncRNA expression levels, processing, or on the secondary structure of lncRNAs which results in cancer development and progression as well as the alteration of drug responses (Cheetham et al., 2013, Ling et al., 2015, Pan et al., 2016). Dysregulation in lncRNAs expression profile has been demonstrated by high throughput analysis in many tumor cells (Gupta et al., 2010, Schmidt et al., 2011, Yang et al., 2012). The lncRNA growth arrest-special 5 (GAS5 ) is a critical tumor suppressor lncRNA in many types of human cancers, located on chromosome 1q25.
A large body of evidence has shown that GAS5 is down-regulated in multiple cancers, including breast cancer, osteosarcoma, colorectal cancer, bladder cancer, prostate cancer, pancreatic cancer, lung cancer, gastric cancer, glioma, hepatocellular carcinoma, cervical cancer and pleural mesothelioma (Zheng et al., 2016, Li et al., 2017, Li et al., 2018c, Guo et al., 2017). Several investigations have shown that GAS5 has the potential to act as a biomarker for metastasis, prognosis, and cancer susceptibility (Sun et al., 2014, Kong et al., 2016, Tu et al., 2014). Previous studies have considered the possible association of lncRNA GAS5 rs145204276 polymorphism with cancer risk. It has been shown that this novel indel (insertion /deletion) polymorphism in the promoter of lncRNA GAS5could modulate colorectal cancer risk through GAS5 expression (Kong et al., 2016). However, there are some inconsistencies in the results among different studies (Li et al., 2018c, Li et al., 2017, Tao et al., 2015, Xu et al., 2018, Yuan et al., 2018, Zheng et al., 2016, Zhu et al., 2017, Zhu et al., 2016, Tang et al., 2019). Hence, we conducted a meta-analysis including recent eligible studies to evaluate the association of lncRNA GAS5 rs145204276 polymorphism and cancer risk.