Impact of CCL4 gene polymorphisms upon the progression of lung cancer in a Han Chinese cohort

Abstract

Lung cancer is the most common malignancy in China and has a low survival rate amongst Han Chinese. The high mortality is largely attributed to late-stage diagnosis, when treatment is largely ineffective. Identification of genetic variants could potentially assist with earlier diagnosis and thus more effective treatment. Chemokine (C–C motif) ligand 4 (CCL4) plays a critical role as a chemoattractant in tumor development, metastasis and angiogenesis. In this study, we explored three CCL4 single nucleotide polymorphisms (SNPs) (rs1634507, rs1719153, and rs10491121) in 538 patients with lung cancer and 370 healthy, cancer-free controls. Carriers of the GT + TT heterozygote of rs1634507 had a lower risk of lung cancer than wild-type (GG) carriers, while the presence of the AG + GG heterozygote at rs10491121 was associated with a higher risk of lung cancer compared with having the AA genotype. The G/A/G and T/A/A CCL4 haplotypes significantly reduced and increased the risks for lung cancer, respectively. Our study is the first to document correlations between CCL4 polymorphisms and lung cancer development and progression in people of Han Chinese ethnicity.

The Association of CCL4 rs1634507 and rs10491121 Polymorphisms with Susceptibility of Oral Squamous Cell Carcinoma in an Iranian Population: A Case-Control Study

“…For example, Wang et al (14) identified the A/G homozygotes of CCL4 rs1049-1121 polymorphism was associated with a lower risk for hepatocellular carcinoma. Another study (28) reported that T/A/A CCL4 haplotype increased the risk of lung cancer in a Chinese population. Hua et al (29) showed that ccl4 upregulated the VEGF-A expression through activating STAT3, increasing the progression and metastasis of endometrial carcinoma.…”

Association of CCL4 rs10491121 and rs1634507 gene polymorphisms with cancer susceptibility: trial sequential analysis and meta-analysis

“…CCL4 is essential for inflammation, tumorigenesis, and other immune responses, particularly tumor growth, metastasis, angiogenesis, and invasion Meta-analysis of the correlation between rs1634507 polymorphism of the CCL4 gene and cancer susceptibility (G vs. T). (20-23), thus making it closely related to the pathogenesis of various cancers (14). CCL-4 expression reportedly increases on the surface of prostate cancer cells, which causes changes in the integrin pathway and exacerbates the development and metastasis of prostate cancer.…”

“…It can bind to CCR5, a seven-transmembrane G protein coupled receptor, on the cell surface ( 3 ). CCL4 is essential for inflammation, tumorigenesis, and other immune responses, particularly tumor growth, metastasis, angiogenesis, and invasion ( 20 – 23 ), thus making it closely related to the pathogenesis of various cancers ( 14 ). CCL-4 expression reportedly increases on the surface of prostate cancer cells, which causes changes in the integrin pathway and exacerbates the development and metastasis of prostate cancer.…”

“…We retrieved a total of 152 relevant papers and finally included seven case-control studies after a stratified screening process. These seven studies encompassed 3559 cases and 4231 controls (11)(12)(13)(14)(16)(17)(18). Among them, CCL4 rs10491121 polymorphisms were discussed in all seven studies and CCL4 rs1634507 polymorphisms were discussed in five case-control studies, encompassing 2109 cases and 3021 controls.…”

“…In breast cancer patients, the probability of cancer metastasis to lymph nodes is lower in patients with the genotype AG or GG of rs10491121 than in those with genotype AA of rs10491121 ( 13 ). The risk of developing lung cancer is higher in individuals with genotype GT or TT of rs1634507 than in those with genotype AA of rs1634507 ( 14 ).…”