Abstract
Folic acid and methylenetetrahydrofolate reductase (MTHFR) may affect the development of human cancer. However, few studies have evaluated folate intake and MTHFR in susceptibility to and prognosis of patients with ovarian cancer. We conducted a prospective case-control study in 215 ovarian cancer patients and 218 controls (all Chinese) between Jan. 2004 and Jan. 2007. MTHFR C677T genotyping was done by PCR-RFLP. All patients were followed up until Dec. 2010. We found a 2.43-fold increased risk of ovarian cancer among MTHFR 677TT carriers, and a decreased risk of ovarian cancer in individuals with high folate intake (OR = 0.54, 95% CI = 0.32–0.94). Cox regression survival analysis showed that among the ovarian cancer patients, those carrying the 677TT genotype had a higher risk of death (HR = 2.17, 95% CI = 1.20–4.79), while high folate intake was associated with a lower risk of death (HR = 0.43, 95% CI = 0.33–0.88). Moreover, MTHFR 677CC carriers with higher folate intake showed a lower risk of death from ovarian cancer (HR = 0.32, 95% CI = 0.27–0.82). In summary, high folate intake may lessen susceptibility and improve the prognosis of ovarian cancer patients, while the MTHFR 677TT genotype appears to increase ovarian cancer risk and worsen its prognosis in a Chinese population.
Highlights
Ovarian cancer is one of the most deadly gynecological cancers worldwide [1]
We further explored the association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms and ovarian cancer prognosis according to folate intake level (Table 4)
Our results indicate that MTHFR C677T polymorphisms are associated with susceptibility to ovarian cancer, and high folate consumption with a decreased risk of ovarian cancer
Summary
Ovarian cancer is one of the most deadly gynecological cancers worldwide [1]. China has a relatively low ovarian cancer incidence of 3–5 per 105 females, which is about one-fourth the rate in northern Europe [2]. Possible risk factors for ovarian cancer include family history, tobacco smoking, infertility, low parity, and hormone replacement therapy, while oral contraceptive use and fewer menstrual cycles are associated with decreased risk [2,3] Deficiency of nutrients, such as vitamins and microelements, has been associated with increased risk for ovarian cancer, whereas high fruit and vegetable intake may help prevent the disease [4]. Since a folate pool imbalance and impaired repair mechanisms may result in DNA instability and strand breaks, and inactive MTHFR C677T may accelerate the carcinogenesis process of DNA hypomethylation under folate deficiency conditions, we hypothesized that folate deficiency and inactive MTHFR C677T may influence both susceptibility to and progression of ovarian cancer We tested this idea with a case-control study and a case-only cohort study in a Chinese population
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