A polymorphism at miRNA-122-binding site in the IL-1α 3′UTR is associated with risk of epithelial ovarian cancer

Abstract

We aimed to investigate the association between rs3783553 polymorphism and susceptibility to epithelial ovarian cancer in a Chinese population and discussed the risk factors associated with survival time. In a case-control study, 301 patients diagnosed with epithelial ovarian cancer and 240 healthy controls were genotyped for rs3783553 polymorphism. Survival time of ovarian cancer patients was explored by Kaplan-Meier analysis and Cox proportional hazards modeling. The distributions of genotype and allele frequencies were significantly different between cases and controls. The variant homozygote (ins/ins) was associated with a significantly reduced risk of ovarian cancer. The patients with del/ins polymorphism seemed to be diagnosed "earlier" (FIGO stage I-II) and be more likely to achieve optimal cytoreductive surgery. Advanced FIGO stage (stages III-IV) and non-optimal cytoreductive surgery (residual tumor <1 cm) were poor prognostic factors in the univariate analysis. However, optimal cytoreductive surgery was found to be the only independent significant prognostic factor. This study suggests that rs3783553 polymorphism may be involved in the susceptibility to epithelial ovarian cancer. It may also be related with the tumor stage and the ability to achieve optimal tumor surgery, while the latter predicts the clinical outcomes for patients as the only independent prognostic factor.

Insertion/deletion polymorphism in IL1A 3′‐UTR is associated with susceptibility to endometrial cancer in Chinese Han women

“…Patients with the D/D genotype were approximately 3.0 times more likely to have HPV16‐positive SCCOP tumours. 25 Similarly, our research team demonstrated that rs3783553 was associated with ovarian cancer, cervical carcinoma and pre‐eclampsia . Through the current study, we found that the rs3783553 seemed to also be involved in the susceptibility to EC in Chinese Han women, and the II genotype seemed to be a protective factor for endometrial carcinogenesis, which was in agreement with previous studies.…”

“…The human genes encoding IL‐1α ( IL1A ) and IL‐1b ( IL1B ) are located on chromosome 2. Recently, the rs3783553, a TTCA insertion/deletion polymorphism located in the 3′‐untranslated regions (3′‐UTR) of IL1A , has been demonstrated to be functional, and is suggested to be associated with the risk of many diseases, especially cancers . This insertion allele influences the expression of IL‐1α in vitro and in vivo by disrupting the binding site for microRNA (miRNA)‐122 .…”

“…Thus, the variants in 3′‐UTR of targeted genes may change the strength of miRNA binding, and then may affect the individual's cancer risk. Rs3783553 has been demonstrated to be associated with the risk of gynecologic oncology, including ovarian cancer, cervical carcinoma and other gynecological and obstetrical diseases, such as endometriosis, and pre‐eclampsia . However, there is no research on the relation between this polymorphism and EC.…”

Lack of association between an insertion/deletion polymorphism in IL1A and risk of colorectal cancer

“…reported that the IL1A rs3783553 ins/ins homozygous genotype is associated with a significantly reduced risk of hepatocellular carcinoma. Similarly, decreased risks were found for nasopharyngeal carcinoma (Yang et al, 2011), gastric cancer (Zeng et al, 2014), cervical carcinoma , and epithelial ovarian cancer (Zhang et al, 2014b). Furthermore, patients of this genotype demonstrated a reduced risk of developing stages T3 and T4 of papillary thyroid carcinoma (Gao et al, 2014) and poor cervical carcinoma tumor differentiation .…”

Effect of polymorphism on IL1A to cancer susceptibility: Evidence based on 34,016 subjects

“…In term of rs3783553, it is a contention of a hundred schools of thought. It includes researches on multiple systems of cancer diseases, such as hepatocellular carcinoma, nasopharyngeal cancer, glioma, prostate cancer, gastric cancer, thyroid carcinoma, oral squamous cell carcinoma, cervical cancer, ovarian cancer, colorectal cancer, colorectal cancer, and endometrial cancer [37,[45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61] . Analyzed by ethnicity, most of studies focus on Asians, yet researches direct to Caucasians are also quite a lot.…”