Mannose-binding lectin codon 54 genetic polymorphism and vaginal protein levels in women with gynecologic malignancies

Objectives: Mannose-binding lectin (MBL), an innate immune system component that binds to carbohydrates, activates the complement cascade and promotes destruction of microorganisms and abnormal cells. We determined whether a polymorphism in the MBL gene influences vaginal MBL protein concentrations and the occurrence of gynecologic malignancies. Study design: DNA from 289 women seen in a gynecologic oncology practice and from 126 healthy women was tested for an MBL codon 54 single nucleotide polymorphism by polymerase chain reaction and endonuclease digestion. Vaginal supernatants from 282 of these women were assayed for MBL protein by ELISA. Results: The normal (A,A) genotype was present in 84.1% of 126 healthy women and 85.3% of 95 women with a benign diagnosis as opposed to 70.0% of 70 women with ovarian cancer (p = 0.02). The MBL variant allele (allele B) frequency was 8.7% in healthy women, 8.4% in women with a benign diagnosis and 17.1% in women with ovarian cancer (p = 0.02). Vaginal MBL protein concentrations were highest in women with the A,A genotype, intermediate in A,B heterozygotes (p < 0.0001) and lowest in B,B homozygotes (p =.0097). Conclusion: The MBL 54 polymorphism and reduction in vaginal MBL concentrations may be a risk factor for development of epithelial ovarian cancer.