Role of HER-2 Ile655Val Polymorphism as Universal Cancer Susceptibility Marker among Different Cancers.
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.


METHODS
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.


CONCLUSIONS
In summary, the current study reveals a significant association between cancer susceptibility and the HER-2 Ile655Val polymorphism in all genetic models.
Department of Biosciences, COMSATS Institute of Information Technology, Park Road, Chak Shehzad, Islamabad, Pakistan.
Syeda Kiran
SK
Riaz
Department of General Surgery, Combined Military Hospital, Rawalpindi, Pakistan.
Muhammad Misbah
MM
Rashid
Department of Biosciences, COMSATS Institute of Information Technology, Park Road, Chak Shehzad, Islamabad, Pakistan.
Mahmood Akhtar
MA
Kayani
Department of Biosciences, COMSATS Institute of Information Technology, Park Road, Chak Shehzad, Islamabad, Pakistan.
Muhammad Faraz
MF
Arshad Malik
D044466:Asian People / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D012307:Risk Factors
D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human