Genetic polymorphisms in uridine diphospho-glucuronosyltransferase 1A1 (UGT1A1) and risk of breast cancer

Abstract

Uridine diphospho-glucuronosyltransferase 1A1 (UGT1A1) is involved in catalyzing estrogen, the hormone that plays a central role in the etiology of breast cancer. A common polymorphism [A(TA)₆TAA (allele *1) to A(TA)₇TAA change (allele *28)] in the TATA-box of the promoter region of the UGT1A1 gene has been reported to be associated with a reduced transcription of this gene. We investigated the association of this polymorphism with the risk of breast cancer among 1047 breast cancer cases and 1083 community controls in the Shanghai Breast Cancer Study, a population-based case-control study. Approximately same proportion of cases (12.5%) and controls (13.0%) carried the variant allele *28 in the Chinese population (p= 0.32). When stratified by age, carrying the *28 allele was associated with an increased risk of breast cancer among women aged less than 40 years (odds ratio [OR] = 1.7; 95% CI = 1.0–2.7) but not among women 40 years old and over (OR = 0.8; 0.7–1.1). Only a few women were homozygous for the *28 allele, precluding a detailed gene-dose association analysis. Additional analyses showed that, the elevated risk associated with the UGT1A1*28 allele among young women was primarily seen in women who had a later menarche, short menstrual years, absence of family history of breast cancer, low waist-to-hip ratio, or low body-mass index. These results suggested that the *28 allele in the UGT1A1 gene may be associated with an increased risk for breast cancer among Chinese women under age 40. No significant associations were observed with *28 allele and breast cancer risk by estrogen receptor/progesterone receptor status.