In the world, about 2.4 hundred thousand new ovarian cancer (OC) cases and about 1.5 hundred thousand deaths caused by this disease are reported annually [1]. It is the 7th most common and 5th most lethal cancer among women worldwide [2]. The incidence rates of OC are highest in northern and eastern Europe, and lowest in Asia and Africa [1]. However, in recently the rates are decreased in many high incidence countries but are increased in many previously low incidence countries, such as China [1, 3].
The 5-years survival rates of OC range from 30.3–44.1%, depending on the specific subtypes and stages at the time of diagnosis or treatment [4, 5]. Early detection and treatment of this disease can increase the survival rate of OC. However without specific signs or symptoms at early stages, caused this diseases usually are diagnosed at late stage [6]. The recurrence rate of this disease is also very high, often leading to death of the patient who might have achieved a clinical complete remission after primary therapy [5, 6].
So far, several genetic and non-genetic factors had been found to be associated with OC. Such as, the women with affected first-degree relatives, have a higher risk for OC [7], and the women, whose relatives are diagnosed OC below 50 years old, even have a higher risk [8]. Except that, many gene mutations also have been found in sporadic OC patients, including BRCA [9], BRIP1 [10] and RAD51 [11]. The non-genetic factors are mainly have some relationship with reproductive or hormonal levels. Oral contraceptive use and tubal ligation are protective factors [12, 13]. Older menopausal age, obesity, menopausal hormone therapy use, a history of endometriosis and smoking are all risk factors [14–16].
Chronic inflammation has also been suggested a risk factor for OC [17, 18]. Because, ovulation process induce inflammatory reaction; and some other OC risk factors, including asbestos and talc exposure, endometriosis and pelvic inflammatory disease, are all cause local pelvic inflammation [17]. On the other side, anti-inflammatory medications, acetaminophen and low-dose of aspirin, are also protective factors for OC [19, 20]. Immunotherapies include immune checkpoint blockade and cancer vaccines, also has many special roles in immune recognition and immune regulation of the OC cells [21].
The chemokines are expressed in tumor or stromal cells, can increase tumor angiogenesis and suppress immune-mediated tumor elimination, and associated with many human diseases including cancers, autoimmune and inflammatory diseases [22–24]. As a member of the CXC subfamily of chemokines, C-X-C motif chemokine ligand 1 (CXCL1) is an oncogenic factor in manly cancers [25, 26], and can transactivate EGFR in OC through binds to the G-protein coupled receptor CXC receptor 2 (CXCR2) [27]. It has been found that abnormal expression of CXCL1 is associated with many tumors [28].
So, in this work we investigated variants rs11547681 and rs4074 in the CXCL1 gene for their associations with the risk of OC in the Chinese Han population. We found variant rs11547681 was associated with ovarian cancer, and demonstrated the 5’UTR for the functions of CXCL1. These findings provide novel insights into the roles of CXCL1 factor in etiology and pathogenesis of ovarian cancer.