Cancer greatly affects the global economy and public health. According to statistics, 14 million cancer patients are diagnosed in 2012, and the cancer morbidity is predicted to increase to nearly 22 million in 2030. At present, the cancer pathogenic mechanism remains largely unclear, and cancer is reported as a complicated condition induced by numerous factors, such as genetic factors, smoking, excessive drinking, chemical dyes, high calorific diet, or their combination. Typically, genetic factors are recognized to exert vital parts in cancer risk, with numerous cancer pathogenesis-related genes being identified as the cancer risk genes.
Renin-angiotensin system (RAS) is the hormone signaling pathway, which has been suggested to modulate blood pressure (BP) and cardiovascular homeostasis. Besides, RAS within local tissues is possibly associated with cancer genesis and progression. In brief, renin can release 10 amino acids (aa) in angiotensinogen (AGT) for forming Ang I as well as the great protein (des (Ang I) AGT). Both des (Ang I) AGT and AGT have been recognized as the non-inhibitory serpins inhibiting new blood vessel formation. Then, ACE can eliminate the above 2 aa from Ang I for generating Ang II. Notably, Ang II represents a major RAS active peptide that can promote cell proliferation and new blood vessel formation via angiotensin II type 1 receptor (AGTR1).
AGT gene is 12,068 bp in length and located on chromosome 1q42.2, and there are 4 introns and 5 exons in the gene coding region. Mutations in AGT gene mostly result from thymine nucleotide (T) substitution by cytosine nucleotide (C) at the + 704 position in exon 2. Therefore, the codon 235-encoded methionine (Met) is replaced by threonine (Thr) (also referred to as M235T), and 2 alleles are formed, including 235T (variant type) and 235M (wild type). Altogether 3 genotypes are detected among the population, which are homozygous 235TT and 235MM, as well as heterozygous 235M. As discovered by Paillard and colleagues, AGT-235 T allele elevated the plasma AGT content, which induced smooth muscle proliferation and contraction of small arteries, lipid deposition and hypertrophy of vascular smooth muscle cells (VSMCs), increased norepinephrine production and excited the sympathetic nervous system.
According to previous meta-analysis, the M235T variant in AGT gene is not related to the susceptibility to cancer. But that meta-analysis only involves a small sample size and does not take into account some latest studies. The aim of the present study was to compile case-control research and updated meta-analyses to explore the association between AGT M235T polymorphism and susceptibility for cancer, so as to more accurately assess the cancer risk.