Association of IGF‐1 gene rs2195239 polymorphism with the risk and clinical features of gastric cancer in a Chinese Han population

Abstract Background Recently, a Japanese study investigated the relationship between insulin‐like growth factor‐1 (IGF‐1) gene rs2195239 polymorphism and gastric cancer (GC) risk and found rs2195239 polymorphism did not relate with the risk of GC. However, no Chinese studies have addressed this relationship until now. Thus, the aims of this study were to demonstrate whether IGF‐1 gene rs2195239 polymorphism was linked with the risk and clinical features of GC in a Chinese Han population. Methods In order to verify the link between IGF‐1 gene rs2195239 polymorphism and GC risk, we recruited 361 GC cases and 418 controls in this case‐control study. The genotyping was done by use of a custom‐by‐design 48‐Plex SNP scan TM Kit. Results This study found that IGF‐1 gene rs2195239 polymorphism decreased the risk of GC. Stratified analyses suggested that the significant association was shown in the females, non‐smokers, non‐drinkers, and age <60 years groups for GC. In addition, IGF‐1 gene rs2195239 polymorphism correlated with the tumor size, tumor clinical stage, and pathological types for GC patients. Conclusion To sum up, this study shows that IGF‐1 gene rs2195239 polymorphism is associated with the risk and clinical features of GC patients in this Chinese population.

the IGF-1 levels. 9 Shitara et al 10 indicated that variants in IGF-1 gene were associated with the GC prognosis. Several studies investigated the relationship between rs2195239 polymorphism in IGF-1 gene and different cancer risks [11][12][13] including GC. 14 However, Ennishi et al 14 did not obtain significant results in this Japanese population. In addition, no Chinese study investigated the link between rs2195239 polymorphism and risk of GC in Chinese individuals previously. In order to uncover this potential association, we designed this hospital-based case-control study in a Chinese Han population.

| Subjects
In this case-control study, 361 newly diagnosed and histologically confirmed GC patients and 418 sex-and age-matched controls were recruited from the Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine (Xianyang, China). The individuals with gastritis, other cancers, or gastric ulcers were excluded from this study. The control groups were individuals receiving health examinations in the hospital at the same period.

| Blood sampling and genotyping
According to manufacturer's instructions, genomic DNA of peripheral leukocytes was extracted using the TIANamp Blood DNA Kit (Qiagen). Rs2195239 polymorphism was genotyped by use of a custom-by-design 48-Plex SNP scan TM Kit (Genesky Biotechnologies Inc.). About 10% of selected samples were validated with direct sequencing to verify the genotyping accuracy. 15,16 The concordance of genotypes in the repeated samples was 100%.

| Statistical analysis
Using the chi-square test, the differences in frequency distributions of dichotomous variable between cases and controls were

| Characteristics of the study population
The demographic data of all participants are shown in Table 1

| Association between IGF-1 gene rs2195239 polymorphism and GC risk
Using logistic tests, the link between IGF-1 gene rs2195239 polymorphism and GC susceptibility was analyzed in five genetic models (

| Association between IGF-1 gene rs2195239 polymorphism and clinical features
Next, we explored the relationship between IGF-1 gene rs2195239 polymorphism and clinical features of GC patients (  Note: Bold values are statistically significant (P < .05). R0: no cancer infiltration at the margin; R1: microscopic cancer infiltration; R2: macroscopic cancer infiltration.

| D ISCUSS I ON
In this study, data indicated that IGF-1 gene rs2195239 polymorphism was related to decreased risk for GC in Chinese individuals. In addition, IGF-1 gene rs2195239 polymorphism conferred decreased risk for GC patients among the non-smokers, non-drinkers, seronegative H pylori, and age <60 years groups. Furthermore, rs2195239 polymorphism was related to the tumor size, TNM stage, and adenocarcinoma among GC patients.
Recently, a host of studies explored the potential association between IGF-1 gene rs2195239 polymorphism and various cancer risks. However, they obtained conflicting findings. Canzian et al 20 firstly investigated the relationship between rs2195239 polymorphism and breast cancer (BC) risk in a Caucasian population. They showed that rs2195239 polymorphism was not related to BC risk. 20 Another study from America 13 replicated above negative results.
Although no associations were found between BC risk and IGF-1 gene rs2195239 polymorphism in a Chinese study, they indicated that this SNP influenced on IGF-I activity in local tissues of BC. 21 They also suggested that another SNP of IGF-I gene (rs7965399) was associated with the risk of BC. 21 Two studies from Japan and  24 and multiple myeloma. 11 Regarding GC, only one study from Japan 14 has addressed the relationship between IGF-1 gene rs2195239 polymorphism and GC risk. 25 However, no association was observed in the Japanese population. 25 In this study, we showed that IGF-1 gene rs2195239 polymorphism was related to decreased risk for GC in Chinese Han population, which was in accord with the findings of a recent meta-analysis by Xu et al. 26 Xu et al found that rs2195239 polymorphism reduced the overall cancer risk, as well as decreasing cancer risk in Asian populations. 26 It is obvious that the findings of this study were different from those of the Japanese study. 25  In conclusion, IGF-1 gene rs2195239 polymorphism is associated with decreased risk for GC in this Chinese population.
Further studies in other populations with larger sample sizes are warranted.

ACK N OWLED G M ENTS
None.

AUTH O R CO NTR I B UTI O N S
Pengli Wang and Xiaoyan Zhou conceived of the study and participated in its design. Pengli Wang and Xiaoyan Zhou conducted the systematic literature review. Xiaoyan Zhou performed data analyses.
Pengli Wang and Xiaoyan Zhou drafted the manuscript. All gave final approval and agree to be accountable for all aspects of work ensuring integrity and accuracy.

S TATE M E NT O F H U M A N A N D A N I M A L R I G HT S
All procedures were in line with the ethical standards of our hospital and with the 1964 Helsinki Declaration.

I N FO R M E D CO N S E NT
Informed consents were obtained from the study participants.