CXCL12 and cancer: As the exclusive receptor for CXCL12, CXCR4 has been verified to play an essential role in the progression and prognosis of tumor.[9–12,30,31] The CXCR4 gene is located on chromosome 2q2, and a synonymous polymorphism of CXCR4 (I138I) have been identified that may influence cancer risk.[13,14] Although the hypothesis of the neutral theory of molecular evolution—that some categories of mutation, like synonymous mutations, have too small an effect on fitness to be affected by natural selection—seems intuitively reasonable, over the past few decades the theory has been not applicable.