Polymorphism in the promoter region of lncRNA GAS5 is functionally associated with the risk of gastric cancer - 29/03/18

Doi : 10.1016/j.clinre.2018.01.006

Qianjun Li ^a, Gang Ma ^a, Suhua Sun ^a, Ying Xu ^a, Bingjian Wang ^b,^⁎
^a Department of gastroenterology, Huai’an first people's hospital, Nanjing medical university, Huai’an, China
^b Department of internal medicine, Huai’an first people's hospital, Nanjing medical university, Beijing road West 6, 223300 Huai’an, Jiangsu, China

^⁎Corresponding author.

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Highlights

•	Patients with gastric cancer (GC) were found to have significantly lower rate of genotype del/del of rs145204276 than the controls.
•	The allele del of rs145204276 was significantly associated with a decreased risk of GC.
•	Patients with allele del were less likely to develop lymph node metastasis and distant metastasis.
•	For both tumor tissues and normal tissues, genotype del/del was indicative of remarkably higher expression of GAS5 than genotype ins/ins.
•	SNP rs145204276 plays a protective role in the development of GC possibly through the regulation of GAS5.

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Summary

Background and aims

Previous studies showed that down-regulation of GAS5 was involved in the development of gastric cancer (GC). However, the regulatory mechanism of down-expressed GAS5 in GC remains obscure. We aimed to investigate the role of rs145204276 of GAS5 in the development and metastasis process of GC.

Methods

853 GC patients and 954 healthy controls were recruited. The variant rs145204276 was genotyped and the Chi² test was used to compare the frequency of the genotype and the allele between the patients and the controls. Odds ratio (OR) and 95% confidence intervals (95% CIs) were calculated to estimate the association of rs145204276 with the risk of development and metastasis of GC.

Results

Patients were found to have significantly lower rate of genotype del/del than the controls (7.2% vs. 8.9%, P=0.016). The allele del was significantly associated with a decreased risk of GC (26.4% vs. 30.7%, P=0.005) with an OR of 0.81 (95% CI=0.70–0.94). Patients with allele del were less likely to develop lymph node metastasis (P=0.01), with an OR of 0.75 (95% CI=0.60–0.93). Comparably, rs145204276 was also significantly associated with a decreased risk of distant metastasis of GC (P=0.007; OR=0.55).

Conclusion

We confirmed that rs145204276 of GAS5 is a functional variant associated with the susceptibility and metastasis of GC. It plays a protective role in the development of GC possibly through the regulation of GAS5.

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Keywords : Long non-coding RNA, GAS5, Polymorphism, Gastric cancer, Susceptibility