J Cancer 2019; 10(2):378-387. doi:10.7150/jca.27976 This issue Cite
1. Institute of Suzhou Biobank, Suzhou Center for Disease Prevention andControl, Suzhou 215004, China
2. School of Public Health, Medical College of Soochow University, Suzhou 215123, China
3. Department of Gynecology and Obstetrics, the First Affiliated Hospital of Soochow University, Suzhou 215006, China
4. Department Gerontology, Liuhe Hospital Affiliated to Medical College of Yangzhou University, Nanjing 211500, China
5. DepartmentofPathology,theFirstAffiliatedHospitalofNanjingMedicalUniversity, Nanjing 210029,China
6. Department of Occupational Disease Prevention, Jiangsu Provincial Centerfor Disease Control and Prevention, Nanjing 210009,China
7. Public Health Research Institute of Jiangsu Province, Nanjing 210009, China.
*These authors contributed equally to this article.
Background: Cervical cancer (CCa) is a multifactorial gynecologic disease worldwide. Effects of HER2 polymorphisms, especially those in exonic region, have been investigated in many gynecologic diseases. In this study, we evaluated the influence of functional HER2 polymorphisms on susceptibility and survival of CCa in a Chinese population.
Methods: We genotyped the HER2 exonic polymorphisms by TaqMan in both case-control study (413 CCa patients vs. 396 controls) and survival study (413 CCa patients). Logistic regression and Cox regression were adopted to evaluate the genetic association with the risk and outcomes of CCa, respectively.
Results: In the case-control study, there was no significant difference between patients and controls in either HER2 rs1136201 or rs1058808. However, when combined, these two polymorphisms demonstrated a significant hazardous effect for CCa (P = 0.012). Besides, number of variants was also influential (P trend =0.002). In survival analysis, dominant model of rs1136201 and co-dominant modelof rs1058808 were significantly associated with the survival (P = 0.037 and P =0.028). The combination of rs1136201 and rs1058808 also negatively impacted CCa survival (P = 0.009). Cox regression further revealed the significance of the polymorphism combination (β = 0.38, P = 0.025, HR= 1.47, 95%CI = 1.05-2.05). Functional assay of these polymorphisms demonstrated that rs1058808 G allele was associated with stronger expression of HER2 gene.
Conclusions: Our results suggested that the combination of HER2 rs1136201and rs1058808 was significantly associated with the susceptibility of CCa. Besides, this combination of polymorphism s also substantially impacted the survival of CCa patients.
Keywords: HER2, cervical cancer, tag SNP, polymorphism, susceptibility, survival