Abstract
PurposePrevious studies have reported a significant contribution of NC_000008.10:g.128413305 G>T (rs6983267) single-nucleotide polymorphism (SNP) in the MYC enhancer region to the susceptibility of various cancers. However, the role of rs6983267 SNP in cervical cancer (CC) development and progression has not been demonstrated to date. Therefore, we evaluated the role of rs6983267 SNP in MYC expression in cervical cancers and non-cancerous cervical tissues. In addition, we assessed the role of this SNP in the development and progression of CC.MethodsUsing high-resolution melting analysis, we evaluated rs6983267 SNP frequency in women diagnosed with cervical squamous cell carcinoma (SCC) (n = 481) and controls (n = 502) in a Polish Caucasian population. Logistic regression analysis was employed to adjust for the effects of age, parity, oral contraceptive use, tobacco smoking, and menopausal status.ResultsDividing patients based on clinical characteristics demonstrated an association of the rs6983267 genotype with tumor stage III and grade of differentiation G2 and G3. The p trend value calculated for the rs6983267 SNP in patients with stage III was 0.0006. We also observed a significant contribution of rs6983267 SNP to tumor grade of differentiation G2 and G3. Additional contributors were oral contraceptive use, smoking, and postmenopausal age. We found statistically significant increase of MYC transcript levels in cervical SCC tissues from carriers of the GG vs. T/T (p < 0.00001), G/T vs. T/T (p = 0.0002), and in the non-cancerous cervical tissues from carriers of the GG vs. T/T (p = 0.00046).ConclusionThe rs6983267 SNP may contribute to the increased MYC expression as well as the spread and rapid growth of cervical SCC as compared to lower grade carcinomas.
Highlights
Cervical cancer (CC) is fourth among the common malignancies, which affect women worldwide [1]
The studied subjects included 481 patients diagnosed with cervical squamous cell carcinoma (SCC), with stage and grade of differentiation evaluated according to the International Federation of Gynecology and Obstetrics (FIGO) classification system and World Health Organization (Table 1)
We did not find a significant association of rs6983267 singlenucleotide polymorphism (SNP) with all patients with cervical SCC, the p trend value calculated for the rs6983267 polymorphism was ptrend = 0.146
Summary
Cervical cancer (CC) is fourth among the common malignancies, which affect women worldwide [1]. The cervix is composed of an ectocervix which is covered by stratified squamous epithelium, and an endocervical canal consisting of mucus-secreting columnar epithelium [1, 2]. The ectocervix is more predisposed to transformation and development of squamous cell carcinoma (SCC), while the endocervix is more predisposed to adenocarcinomas [1, 2]. Less common histological subtypes of CC include adenosquamous, small cell/neuroendocrine, serous papillary, and clear cell carcinomas of the cervix [1, 2]. Cervical SCC account for approximately 80% of invasive CC cases [1]. All cases of CC result from infection with the oncogenic strains of human papillomavirus (HPV) [3, 4]. The majority of HPV infections are short-lived and resolve spontaneously [5,6,7]
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