Cervical cancer pathogenesis is associated with one-carbon metabolism

Cervical cancer is the most common cancer among women in India and a leading cause of death in these women. Most cases of cervical cancer are associated with human papillomavirus (HPV) infection of the high-risk type. It has been reported that aberrant DNA methylation can be associated with HPV infection and cervical cancer, and folate is directly involved in DNA methylation via one-carbon metabolism. We aimed to study the importance of one-carbon metabolism in the progression of cervical carcinogenesis by examining serum levels of vitamin B-12 (cobalamin), homocysteine, and folate and DNA methylation of tumor suppressor genes CDH1, HIC1, and Retinoic acid receptor beta (RAR beta) amid these women ranging from normal to squamous intraepithelial neoplastic lesions (SIL) to cervical cancer. Blood and tissue samples were collected from normal (n = 35), SILs (n = 27), and cervical cancer patients (n = 38) in the age group of 26-70 years. Measurement of serum vitamin B-12, folate, and homocysteine were done using kits (Immulite). Promoter methylation was examined using methylation-specific PCR. The frequency of promoter hypermethylation for all the three tumor suppressor genes CDH1, HIC1, and RAR beta showed an increasing trend from normal to dysplastic to invasive cervical cancer (p < 0.05). We observed that lower folate and vitamin B-12 status were associated with HPV infection. Taken together, our findings suggest a role of folate and vitamin B-12 in modulating the risk of cervical cancer and HPV infection. CDH1, HIC1, and RAR beta genes can be used as potential biomarkers of cervical cancer risk assessment.