Background: Genetic and expression anomaly of HER-2 have been frequently observed in different cancers. However, an overall association of HER-2 polymorphism (Ile655Val) with available cancer studies has not yet been explored. In the present study, a probable correlation of HER-2 Ile655Val polymorphism with 6 major types of cancers including breast, lung, gastric, ovarian, thyroid and uterine has been collectively assessed.
Methodology: Extensive data mining was performed using online available medical research databanks including Pubmed, Ovid, Medline and Embase. Research articles were retrieved based on common keywords "HER-2, polymorphism, (SNP) and cancer (including breast, gastric, lung, ovarian, thyroid and uterine). A database was maintained and updated for case control studies of HER-2 genotype Ile655Val (rs1136201) information until February 2015. Based on selection criteria, a total of 41 studies containing 37,111 subjects (17845 patients, 19266 controls) were selected for thorough insight about HER-2.
Results: A significant risk association of HER-2 Ile655Val polymorphism was observed in different types of cancer using various genetic models (co-dominant heterogeneous Ile/Val vs Ile/Ile; OR=1.1, 95% CI = 1.01-1.16, P = 0.01 and dominant; OR = 1.12, 95% CI = 1.03-1.20, P = 0.0003). Interestingly, a strong correlation of Ile655Val heterogeneity was seen in the stratified subgroup of different population including African-American (co-dominant homogenous Val/Val vs Ile/Ile; OR = 8.7, 95% CI = 2.5-30.4, P = 0.0001, dominant; OR = 1.3, 95% CI = 1.03-1.7, P = 0.003; recessive; OR = 8.3, 95% CI = 2.4-28, P = 0.0002), Caucasians (co-dominant heterogeneous Ile/Val vs Ile/Ile; OR = 1.1, 95% CI = 1.0 - 1.2, P = 0.03, dominant; OR = 1.12, 95% CI = 1.0-1.2, P = 0.01). However, in Asian ethnic group, Ile655Val polymorphism lacked a significant association with cancer. This may be attributed to limited studies explored so far.
Conclusion: In summary, the current study reveals a significant association between cancer susceptibility and the HER-2 Ile655Val polymorphism in all genetic models.