Recent studies have suggested that single-nucleotide polymorphisms (SNPs) located in the cluster might be linked to cancer risk. In this meta-analysis association study, we sought to quantitatively measure the strength of this association with cancer susceptibility in the overall analysis. Relevant publications were retrieved through a literature search in Web of Science, Medline, PubMed, Scopus, and Google scholar databases (updated January 22, 2020). Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were estimated under different genetic contrasted models. Our findings showed that rs4705341 (under allelic, codominant AA, dominant, and recessive), rs4705342 (under allelic, codominant TC, codominant CC, dominant, and recessive), and rs353292 (under allelic, codominant CT, and dominant) significantly decreased cancer risk. However, we did not find any association between the rs4705343, rs353293, rs3733845, and rs3733846 variants and cancer risk under any genetic models. The stratified analysis by cancer type showed that the rs41291957 and rs4705342 variants showed protective effects against colorectal- and prostate cancers, respectively. Our findings support the association between some cluster variants and cancer risk. Replication large-scale studies on different races are encouraged to precisely delineate such associations.