Background: Gastric cardia adenocarcinoma (GCA) is a common malignant tumor of the digestive tract with a high incidence in China. Genetic factors such as single nucleotide polymorphisms (SNPs) may contribute to the carcinogenesis of GCA. Methods: We conducted a hospital-based case-control study to evaluate the genetic association of functional SNPs with susceptibility to GCA development. A total of 330 GCA cases and 608 controls were recruited for this study. The SNPs OPG rs3102735 T>C and rs2073618 G>C, RANK rs1805034 T>C, and RANKL rs9533156 T>C and rs2277438 A>G were determined using the ligation detection reaction method. Results: Our findings suggest that RANK rs1805034 T>C is associated with susceptibility to GCA, which is more evident among male patients, elderly patients (≥ 60 years), smokers, and patients who do not consume alcohol. Conclusion: Based on our findings, the functional SNP RANK rs1805034 T>C may be an indicator for individual susceptibility to GCA. However, further larger studies with other ethnic populations and tissue-specific biological characterization are required to confirm the current findings.

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