Relationship of the interaction between age and gene polymorphisms with the susceptibility, invasion and metastasis of gastric carcinoma / 中华老年医学杂志

ABSTRACT

Objective To investigate the relationship of the interaction between age and polymorphisms of E-selectin gene A561C, chemokine receptor CCR2 gene A190G with the susceptibility, invasion and metastasis of gastric carcinoma.Methods Based on tumor-node-metastasis (TNM) staging classification, 750 patients with confirmed gastric carcinoma in our hospital from December 2011 to November 2014 were divided into 5 groups stage Ⅰ, stage Ⅱ , stage Ⅲ, stage Ⅳ and stage 0 (n=150, each).No significant difference was observed in gender, ethnicity, birthplace and living habits among the 5 groups.Meanwhile, 750 healthy controls were selected in this study during the same time, and there was no significant difference in gender, ethnicity and birthplace between the healthy controls and patients with gastric carcinoma.The genetic polymorphisms of E-selectin gene A561C and chemokine receptor CCR2 gene A190G were analyzed by polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) in peripheral blood mononuclear cells (PBMs).Results The frequencies of CC (A561C) and GG (A190G) genotypes were 56.5％ and 56.8％ respectively in gastric carcinoma cases and 22.8％ and 23.1％ respectively in healthy controls, with statistically significant differences in the distribution frequencies between the two groups (P＜0.01 for all).The risk for gastric carcinoma significantly increased in subjects with CC (A561C) genotype (OR=4.4038, 95％CI=2.9421-7.2397) and in GG (190A/G) genotype (OR=4.3852, 95％ CI =2.8207-7.4942).Combined analysis of the polymorphisms showed that the distribution frequency of CC (A561C) genotype / GG (190A/G) genotype in gastric carcinoma cases and healthy controls was 46.4％ and 11.9％ respectively (P＜0.01).The positive interactions of age with CC (A561C) genotype and GG (190A/G) genotype for the risk of invasion and metastasis of gastric carcinoma were found (γ＞1 for both).The distribution frequencies of CC (A561C) genotype and GG (190A/G) genotype were 50.0％ and 50.0％ in stage Ⅰ , 63.4％ and 64.0％ in stage Ⅱ ,69.3％ and 69.3％ in stage Ⅲ, 76.7％ and 77.3％ in stage Ⅳ, and 23.3％ and 23.3％ in stage 0 respectively.Statistically significant differences were found in the distribution frequencies between stage 0 and the other 4 stages (P＜0.01 for all).The risks for the invasion and metastasis of gastric carcinoma were significantly increased in subjects with CC (A561C) genotype (ORⅠ-Ⅳ =3.2857-10.7959) and in those with GG (190A/G) genotype (ORⅠ-Ⅳ =3.2857-11.2101).Combined analysis of the polymorphisms showed that distribution frequency of CC (A561C) genotype / GG (190A/G) genotype had significant differences between the stage Ⅰ ～Ⅳ and stage 0 (39.3％, 53.3％, 59.3％,68.0％ vs.12.0％, P＜0.01).The proportion of elderly subjects were higher in Grade Ⅰ ～Ⅳ than in Grade 0 (51.3％, 62.7％, 70.0％, 75.3％ vs.26.7％, P＜0.01 for all).The risk for invasion and metastasis of gastric carcinoma was significantly increased in elderly patients (ORⅠ-Ⅳ =2.9001 ～8.3986).The positive interactions of age with CC (A561C) genotype and GG (190A/G) genotype for the risk of invasion and metastasis of gastric carcinoma were found (γ＞ 1 for All).Conclusions Age and E-selectin gene A561C (CC) and chemokine receptor CCR2 gene A190G (GG) are the risk factors for the invasion and metastasis of gastric carcinoma, and the interactions between age and genetic polymorphisms increase the risk of invasion and metastasis of gastric carcinoma.