Association of polymorphisms in MALAT1 with the risk of endometrial cancer in Southern Chinese women

Abstract

Background: Endometrial cancer is the most common gynecologic malignancy worldwide. Polymorphisms in MALAT1 have been demonstrated to play critical roles in cancer. However, the roles of MALAT1 polymorphisms in the etiology of endometrial cancer have not been well documented. Methods:We genotyped three MALAT1 polymorphisms in 249 endometrial cancer cases and 446 cancer-free female controls using quantitative polymerase chain reaction with TaqMan probes. To estimate the association between MALAT1 polymorphisms (rs591291 C>T, rs664589 C>G, and rs4102217 G>C) and the risk of endometrial cancer, an unconditional logistic regression model was conducted to calculate the odds ratio (OR) and the 95% confidence interval (CI), adjusting for surgery history, menopause, number of deliveries, BMI, and FIGO stage. Results:We found that the MALAT1 rs664589 C>G polymorphism was significantly associated with endometrial cancer risk (heterogeneous: adjusted OR = 0.57, 95% CI = 0.34-0.93, P = .026; homogenous: adjusted OR = 3.74, 95% CI = 1.12-12.45, P = .032; and recessive: adjusted OR = 4.06, 95% CI = 1.22-13.48, P = .022). Stratified analysis further demonstrated that the MALAT1 rs664589 C>G polymorphism significantly increased the risk of endometrial cancer susceptibility in patients with no history of surgery, more deliveries, BMI between 25 and 29.9, and FIGO stages II-III.Compared with the wild-type GCG haplotype carriers, individuals with CGG haplotypes had a higher risk of developing endometrial cancer. Conclusion:The MALAT1 rs664589 C>G polymorphism was associated with a significant increase in endometrial cancer risk. K E Y W O R D S endometrial cancer, MALAT1, risk, single nucleotide polymorphisms 2 of 7 | CHEN Et al.1 | INTRODUC TI ON Endometrial cancer (EC) is the most common cancer among females worldwide. 1 The incidence of EC has seen a significant increase in China. 2 Unopposed estrogen, early menarche, endometriosis, obesity, diabetes, late menopause, hypertension, and nulliparity are now well established as causative agents responsible for endometrial cancer. 3 Although these risk factors are strongly associated with the risk of endometrial cancer, only a small number of women eventually develop endometrial cancer, suggesting that host genetic variations play critical roles in endometrial cancer development.Long non-coding RNAs (lncRNAs) are a class of ncRNAs that are more than 200 nucleotides and are involved in several biological processes. [4][5][6][7][8] Increasing evidence suggests that lncRNAs are associated with tumor genesis, progress, and treatment response. 9,10 Metastasis associated with lung adenocarcinoma transcript-1 (MALAT1) is a long intergenic non-coding RNA (lincRNA), consisting of more than 8000 nts and located on chromosome 11q13. 11,12 Recent studies have shown that abnormal MALAT1 expression influenced cancer cell proliferation, invasion, and/or metastasis in various tumors, such as breast cancer, 13 lung cancer, 14 and gastric cancer. 15 Therefore, MALAT1 has been classified as an oncogene...

Role of MALAT1 in gynecological cancers: Pathologic and therapeutic aspects (Review)

“…Chen et al (73) demonstrated the association of MALAT1 rs664589 C>G polymorphism with the risk of endometrial cancer in Southern Chinese women. It was demonstrated that individuals with CGG haplotypes have a higher risk of developing endometrial cancer compared with the wild-type GCG haplotype carriers (73). Collectively, these findings suggest the potential role of MALAT1 in inducing the development of different gynecological cancers.…”

The Construction and Exploration of the ceRNA Network and Patterns of Tumor-Infiltrating Immune Cells in Kidney Renal Clear Cell Carcinoma

“…In addition to NSCLC, MALAT1 is also present in other malignant tumors. In endometrial cancer, the expression of MALAT1 is negatively correlated with the expression of miR-200c, and its knockdown can promote the expression of miR-200c in cancer cells [28]. Studies have found that MALAT1 can also adjust the expression of miR-140 in prostate cancer cells to change the mRNA and protein expression levels of apoptosis inhibitor protein to promote the occurrence and development of tumors [29].…”

Reflections on the Role of Malat1 in Gynecological Cancer

“… 40 Single nucleotide polymorphisms (SNPs) in Malat1 DNA, such as Rs664589C>G, have been shown to significantly increase the risk of endometrial cancer when tested in tissue samples and peripheral blood and following the application of logistic regression analyses. 41 In addition, the expression levels of Malat1 have been found to be related to tumor type, metastatic lymph nodes, and recurrence rate. 42 …”