Impact of CD44 genetic variants on clinicopathological characteristics of uterine cervical cancer patients

Abstract

CD44 genetic variants have been found to be related to various cancers. However, to date, no study has demonstrated the involvement of CD44 polymorphisms in uterine cervical cancer in Taiwanese women. Therefore, we conducted a retrospective study, consecutively recruiting 113 patients with invasive cancer, 92 patients with high-grade cervical intraepithelial neoplasias, and 302 control women to assess the relationships among CD44 polymorphisms, cervical carcinogenesis, and patient survival. Real-time polymerase chain reaction was used to determine the genotypic distributions of six polymorphisms: rs1425802, rs187115, rs713330, rs11821102, rs10836347, and rs13347. The results revealed that women with the mutant homozygous genotype CC exhibited a higher risk of invasive cancer compared to those with the wild homozygous genotype TT [p=0.035; hazard ratio (HR)=10.29, 95% confidence interval (95% CI)=1.18-89.40] and TT/TC [p=0.032; HR=10.66, 95% CI=1.23-92.11] in the CD44 polymorphism rs713330. No significant association was found between CD44 genetic variants and clinicopathological parameters. Among the clinicopathological parameters, only positive pelvic lymph node metastasis (p=0.002; HR=8.57, 95% CI=2.14-34.38) and the AG/GG genotype compared to AA (p=0.014; HR=3.30, 95% CI=1.28-8.49) in CD44 polymorphism rs187115 predicted a higher risk of poor five-year survival, according to multivariate analysis. In conclusion, an important and novel finding revealed that Taiwanese women with the AG/GG genotype in CD44 polymorphism rs187115 exhibited a higher risk of poor five-year survival.

Keywords: 5 years survival rate; CD44; cancer of uterine cervix; genetic variants; rs187115.

Figure 1

Five years survival rate based on the only significant polymorphism rs187115 among CD44 genetic variants and only significant clinicopathological parameter pelvic lymph node metastasis in multivariate Cox proportional hazard model. (A) genotypes AG/GG exhibit more risk of poor 5 years survival rate as compared to genotype AA (p=0.014; hazard ratio: 3.30, 95% confidence: 1.28-8.49) (B) positive pelvic lymph node metastasis exhibits more risk of poor 5 years survival rate as compared to negative pelvic lymph node metastasis (p=0.002; hazard ratio: 8.57, 95% confidence: 2.14-34.38). Statistical analysis: Cox proportional hazard model after adjusting for various CD44 genetic variants and clinicopathological parameters.