Study on TFF1 and PALB2 gene variants associated with gastric carcinoma risk in the Chinese Han population

Introduction

Gastric carcinoma (GC) is one of the most fatal diseases due to its metastasis and resistance to therapy [1] . GC is the fifth most common malignant tumor in the world, second only to lung cancer, breast cancer, colorectal cancer, and prostate cancer [2] . In 2018, there were more than one million new cases of GC worldwide, and approximately 783,000 people died of GC [3] , making it the third leading cause of death [4] . Approximately half of the world’s GC cases and deaths occur in China, imposing a heavy burden on China’s economic conditions and health care [5] .

Studies have confirmed that Helicobacter pylori infection, age, high salt intake, and a diet low in fruits or vegetables are major risk factors for GC [67] . As one of the most common sources of infection in the stomach, Helicobacter pylori can adapt to the extremely acidic conditions of the gastric environment, establish persistent infection, and relieve host function, which is the main risk factor for the development of GC [8] . Evidence shows that being overweight increases the risk of gastric cardia cancer [9] , possibly because Helicobacter pylori is more common in obese people [10] . At present, numerous studies have also shown that chronic alcohol consumption [11] , smoking [12] , and high blood sugar [13] increase the risk of GC. Therefore, it is particularly important to study the susceptibility factors for GC.

The above risk factors have a great impact on GC, most of which are sporadic. Additionally, more and more evidence suggests that GC is also affected by genetic susceptibility. Exome array analysis showed that SPOCD1 gene polymorphism is related to the risk of GC by regulating the proliferation and invasive activity of GC cells [14] . A genome-wide association study (GWAS) investigated the impact of GC susceptibility sites on the prognosis of GC in Asians, which found that one single nucleotide polymorphism (SNP) rs2274223 of the PLCE1 gene may lead to the deterioration of patients’ conditions [15] . Trefoil factor 1 ( TFF1 ), located on 21q22.3, is a 6.5 kDa secreted protein that is expressed predominantly in normal gastric mucosa and maintains the functional integrity of gastric mucosa [1617] . Down-regulation of TFF1 expression caused by demethylation of the TFF1 promoter promotes the occurrence of GC [18] . In conclusion, there is a certain molecular basis between the TFF1 gene and GC. Another gene we studied is the Partner and localizer of BRCA2 ( PALB2 ) gene, which is located on 16p12.2. Currently, PALB2 has been found to act as a tumor suppressor gene in breast and pancreatic cancers [19] . A study on the Greek population showed that variants in PALB2 increase breast cancer risk [20] . Notably, recent studies have shown that PALB2 is a familial GC gene [21] . The above reports demonstrate that the study of PALB2 gene polymorphisms and the risk of GC can provide a new direction for the clinical treatment of GC.

Based on the above theoretical support, we conducted a case-control study to evaluate the relationship between TFF1 and PALB2 gene polymorphisms and GC susceptibility and to investigate whether TFF1 and PALB2 gene polymorphisms affect GC risk, so as to provide more effective biomarkers and data support for research on GC.

2 Materials and methods