Ethnic differences in breast cancer risk: a possible role for pregnancy levels of alpha-fetoprotein?

Abstract

Breast cancer incidence rates are up to five times higher in white women in the United States compared with Asian women in China and Japan. A search for factors that modify estrogen's biological effect differentially between ethnic groups may add to the understanding of international variations in breast cancer risk. Recent evidence indicates that alpha-fetoprotein, a glycoprotein produced by the fetal liver, has important antiestrogenic properties. During pregnancy, alpha-fetoprotein reaches peak concentrations in maternal serum during the third trimester. We compared pregnancy levels of alpha-fetoprotein in a population with high risk of breast cancer (Boston, MA) and low risk (Shanghai, China). Blood samples were collected around the 16th week and around the 27th week of gestation among women enrolled from March 1994 to October 1995. The number of specimens available for alpha-fetoprotein analysis was 1,033. Alpha-fetoprotein levels, adjusted for gestational length, were substantially higher in Shanghai compared with Boston women at both time points. When adjustments were made for prepregnancy weight, parity, offspring's sex and maternal age, alpha-fetoprotein levels remained 13% higher in Shanghai at 16 weeks of pregnancy but not at 27 weeks. These findings may explain, at least in part, the difference in breast cancer risk between Chinese and American women. On the population level, alpha-fetoprotein may influence risk by modifying the effect of biologically active estrogens both in the mother and in female offspring.