New concept of the Axin2 rs2240308 polymorphism and cancer risk: an updated meta-analysis

Abstract

Previous meta-analyses reported that the variant T allele of Axin2 rs2240308 is associated with a decreased cancer risk. However, more recent findings have been inconsistent. Therefore, we carried out an updated meta-analysis to examine whether this polymorphism is still associated with a decreased cancer risk. Twelve articles, including 14 case-control studies (2,215 cases and 2,481 controls), were included in our study. Surprisingly, different from previous meta-analyses, no significant association between Axin2 rs2240308 polymorphism and cancer risk was observed (dominant model: OR=0.85; 95% CI=0.68-1.06). In further stratified analyses, rs2240308 was significantly associated with a decreased cancer risk only in Asians (dominant model: OR=0.76; 95% CI=0.66-0.88), while for Caucasians the variant showed no significant association with cancer risk (dominant model: OR=1.09; 95% CI=0.67-1.76). Moreover, the rs2240308 variant exhibited a significant association with a decreased risk of lung cancer and prostate cancer. These findings provided new evidence that differed from previous meta-analyses; Axin2 rs2240308 may not modify general cancer susceptibility. Similar with previous meta-analyses, our analysis indicated that Axin2 rs2240308 may modify cancer susceptibility in an ethnicity- and/or type-specific manner. These findings indicate that further replication studies with large sample sizes are warranted to re-evaluate the relationship between Axin2 rs2240308 and cancer risk, especially in Caucasians.

Variations in AXIN2 predict risk and prognosis of colorectal cancer

“…24 Significant differences have been reported in the association between rs2240308 and the risk of cancer for type of cancer and ethnic group. 17 Then, while it has been reported that rs2240308 increased the risk of lung cancer especially in Asian population, 5 a recent analysis indicated that AXIN2 148 C > T (rs2240308) variant may be associated with decrease lung risk in Asian and Caucasian populations. 25 Therefore, further studies in Latin American population should be conducted to explain the association between AXIN2 polymorphisms and CRC.…”

“…This polymorphism (rs2240308, c.148 G > A) results in an amino acid change from proline to a serine. Although, rs2240308 has been associated with hypodontia and cancer in different populations, 16,17 in Iranian subjects, this polymorphism was related with decreased risk for CRC. 18 The inconsistent results reported in literature are explained by racial differences.…”

“…18 The inconsistent results reported in literature are explained by racial differences. 17 In Latino populations, genetic studies relating hypodontia and CRC are scarce, although AXIN2 rs2240308 was recently associated with CRC in Mexican population. 19 Therefore, identifying and analyzing genetic mutations in CRC and hypodontia can provide relevant information about the biological behavior of both diseases.…”

New insights of the correlation between AXIN2 polymorphism and cancer risk and susceptibility: evidence from 72 studies

“…P < 0.1 meant a significant heterogeneity, and if so, we used the random effects model (DerSimonian and Laird methods) to summarize the data [20]; if not, the fixed effect model (Mantel-Haenszel method) was selected [21]. Hardy-Weinberg equilibrium (HWE) was performed for sensitivity analysis [22].…”

New insights into the association between AXIN2 148 C/T, 1365 C/T, and rs4791171 A/G variants and cancer risk

“…If P < 0.05, indicating that a significant heterogeneity was found, we employed the random-effects model (DerSimonian–Laird method) [34]. On the other hand, the fixed-effects model (Mantel–Haenszel method) was carried out [35]. We adopted qualitative funnel plot to assess possible publication bias by calculating the standard error of log(OR) for each research plotted against its log(OR).…”