A Molecular Epidemiology Study On The Association Of CCND1 G870A Gene Polymorphism And The Susceptibility Of Cervical Cancer And Ovarian Cancer

Cervical cancer is the second most common cancer among women worldwide, with an estimated 493,000 new cases and 274,000 deaths in the year 2002, and 83% of the cases had occurred in developing countries. Although there have been substantial declines in both incidence and mortality rates in the past 30 years, >100,000 cervical cancer cases are diagnosed in China every year. Epidemiologic and laboratory-based studies have identified the infection with one of 15 high-risk, or oncogenic, human papilloma virus (HPV) types as a necessary but not sufficient cause of cervical cancer. The prevalence of genital HPV infection in developing countries is very high in young women, but most of the infected regress without intervention. Given the mounting evidence that long-term HPV infection is a prerequisite for cervical carcinogenesis, genetic variations that influence the host hereditary susceptibility may determine the outcome of high-risk HPV infection.Ovarian cancer (204,000 cases and 125,000 deaths) is the sixth most common cancer and the seventh cause of death from cancer in women (4.0% of cases and 4.2% deaths). The overall 5-year survival remains poor (30%), despite improvements in surgical treatment and cancer chemotherapy. Thus, even after adequate surgery and chemotherapy about 50% of patients will develop recurrence within 2 years and will eventually die. Prognostic markers presently available are not sufficiently reliable to identify the patients who will suffer a particularly poor outcome. The development of novel prognostic markers related to tumor cell biology is therefore needed if substantial improvement is to be made.Cyclin D1, a member of the D-type cyclin family, is a key cell-cycle regulatory protein involved in the restriction point early in the G1-phase . The CCND1 gene is located on chromosome 11q13, which has 5 exons and 4 introns. A common G870A polymorphism in exon 4 of the CCND1 gene is known to modulate the frequency of alternate splicing and probably reduce transcript levels. Recent studies showed that the CCND1 G870A polymorphism is associated with elevated risks of breast and endometrial cancer. In the present study, we conducted a case–control study of the CCND1 G870A polymorphisms and risk of cervical cancer and ovarian cancer risk in Chinese populations and also performed a meta-analysis of the published studies to identify the evidence of an association between genetic variations in the CCND1 G870A and risk of developing cervical cancer. Purpose: Cyclin D1 (CCND1) is a key regulatory protein at the G1/S checkpoint of the cell cycle. We hypothesized that the CCND1 G870A polymorphism is associated with risk of cervical cancer and performed a meta-analysis from eligible studies to evaluate this relationship. Methods: In a case-control study of 300 patients with newly diagnosed cervical cancer and 312 cancer-free controls frequency-matched by age, we genotyped the G870A polymorphisms of CCND1 gene by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. A meta-analysis was performed from 5 case-control studies including our results. Results: No significant association was observed between the CCND1 G870A polymorphism and cervical cancer risk. The meta-analysis did not show a significant risk of cervical cancer in the CCND1 G870A polymorphism. However, in the stratified analyses by race, we found that individuals with the AA or AA/AG genotypes had a significant increased risk compared with those with GG genotype in Asians. Conclusion: The CCND1 G870A polymorphism may contribute to the etiology of cervical cancer in Asian population. Objective:To investigate the relationship of the CCND1 G870A polymorphism and the risk of ovarian cancer.Methods:In a case-control study of 107 patients with newly diagnosed ovarian cancer and 114 cancer-free controls frequency-matched by age, we genotyped the G870A polymorphisms of CCND1 gene by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.We further stratified the age, age at menarche, age at first live birth, parity, number of abortion and menopausal status of cases. Results:No significant association was observed between the CCND1 G870A polymorphism and ovarian cancer risk. Conclusion:Our data showed that no obvious association was found between the CCND1 G870A polymorphism and ovarian cancer risk in Chinese population.