Sex steroid hormones influence the risk for cervical cancer: modulation by haptoglobin genetic polymorphism

Sex steroid hormones ingestion (contraceptives and replacement therapy) may influence cervical carcinogenesis. Haptoglobin (Hp), an acute phase protein that has genetic polymorphism, can influence immune response to tumor. Our objective was to study the influence of haptoglobin genetic polymorphism on the risk for development of cervical cancer dependent on sex steroid hormones. A total of 492 Caucasian women, 196 pathologic [high-grade squamous intraepithelial lesions and invasive cervical cancer (HSIL + ICC)], ranging in age from 18 to 81 years, were phenotyped for plasma Hp using a polyacrylamide gel electrophoresis method. The effect of the interaction between the Hp genetic phenotype and steroid hormone therapy was analyzed using a multinomial logistic regression. Hp 1/1 genetic phenotype was associated with the risk for cervical cancer of steroid hormone ingestion: general risk odds ratio (OR)=5.388, P < 0.001; for the interaction with carriers of Hp 1/1, OR=6.765, P < 0.001; with carriers of Hp 2/1, OR=6.499, P < 0.001; and with carriers of Hp 2/2, OR=3.903, P = 0.001. The linear trend of risks that result from that interaction is also significant (χ2 = 31.8, P < 0.001). The higher risk for HSIL + ICC observed in carriers of increasing allele 1 of Haptoglobin probably results from the intense immune suppressor effect of this form of Hp, in addition to that of steroid hormones ingestion.