Associations of Genetic Variants in the PSCA, MUC1 and PLCE1 Genes with Stomach Cancer Susceptibility in a Chinese Population

Abstract

BackgroundSeveral genetic variants including PSCA rs2294008 C>T and rs2976392 G>A, MUC1 rs4072037 T>C, and PLCE1 rs2274223 A>G have shown significant association with stomach cancer risk in the previous genome-wide association studies (GWASs).MethodsTo evaluate associations of these SNPs in the Han Chinese, an independent hospital based case-control study was performed by genotyping these four polymorphisms in a total of 692 stomach cancer cases and 774 healthy controls acquired by using frequency matching for age and gender. False-positive report probability (FPRP) analysis was also performed to validate all statistically significant findings.ResultsIn the current study, significant association with stomach cancer susceptibility was observed for all the four polymorphisms of interest. Specifically, a significant increased stomach cancer risk was associated with PSCA rs2294008 (CT vs. CC: adjusted OR = 1.37, 95% CI = 1.07–1.74, and CT/TT vs.CC: adjusted OR = 1.30, 95% CI = 1.03–1.63), PSCA rs2976392 (AG vs. GG: adjusted OR = 1.30, 95% CI = 1.02–1.65, and AG/AA vs. GG: adjusted OR = 1.26, 95% CI = 1.00–1.59), or PLCE1 rs2274223 (AG vs. AA: adjusted OR = 1.48, 95% CI = 1.15–1.90, and AG/GG vs. AA: adjusted OR = 1.45, 95% CI = 1.14–1.84), respectively. In contrast, MUC1 rs4072037 was shown to decrease the cancer risk (CT vs. TT: adjusted OR = 0.77, 95% CI = 0.60–0.98). Patients with more than one risk genotypes had significant increased risk to develop stomach cancer (adjusted OR = 1.30, 95% CI = 1.03–1.64), when compared with those having 0–1 risk genotypes. Stratified analysis indicated that the increased risk was more pronounced in younger subjects, men, ever smokers, smokers with pack years ≤ 27, patients with high BMI, or non-cardia stomach cancer.ConclusionsThis study substantiated the associations between four previous reported genetic variants and stomach cancer susceptibility in an independent Han Chinese population. Further studies with larger sample size and different ethnicities are warranted to validate our findings.

PSCA s2294008 C>T and rs2976392 G>A polymorphisms contribute to cancer susceptibility: evidence from published studies

“…Overall, there were 32 studies investigating the association between PSCA rs2294008 C>T polymorphism and cancer susceptibility, consisting of 30028 cases and 38765 controls [8, 9, 14-35, 39-43], and 14 studies performed on the relation between PSCA rs2976392 G>A polymorphism and overall cancer susceptibility, with 8190 cases and 7176 controls [8, 14-17, 19, 24, 29, 36-39, 43]. The main characteristics of the studies included in this meta-analysis were summarized in Table 1.…”

“…The studied cancer type included gastric cancer [8, 14-17, 20-22, 25, 26, 31, 32, 34, 39, 41-43], bladder cancer [9, 18, 23, 28, 35, 40], prostate cancer [19], esophageal cancer [20, 33], breast cancer [24], colorectal cancer [27], and gallbladder cancer [29, 30]. In term of ethnicity, 21 studies were performed among Asians, 10 studies among Caucasians, and one study among Africans.…”

“…For the PSCA rs2976392 G>A polymorphism, the number of cases ranged from 44 to 1525 while varying control sample sizes (from 60 to 1397) were also observed among selected studies. The studied cancer type included gastric cancer [8, 14-17, 36-39, 43], prostate cancer [19], breast cancer [24], and gallbladder cancer [29]. Of them, 13 studies were performed among Asians and one among Caucasians.…”

“…The significant associations were reported and validated in some studies among different ethnic populations and different types of cancers [8, 9, 14-43]; however, others failed to replicate such association. The controversy is probably due to different ethnicities, histology types, and relatively small sample size in individual studies.…”

Racial Disparity in Gastrointestinal Cancer Risk

“…Diets rich in fruit and vegetables are suggested to have protective effects against gastric cancer while higher BMI is suggested to be a risk factor for cardia gastric cancer. Among Asians, low penetrance genetic variants in PSCA , PLCE1 , PRKAA1 and MUC1 increase risk for gastric cancer and among Europeans, loss of function of ATM increases gastric cancer risk [34–36]. Inactivating mutations in the E-Cadherin gene ( CDH1 ) leads to hereditary diffuse gastric cancer syndrome in a small fraction of individuals.…”