MicroRNAs: Novel Breast Cancer Susceptibility Factors in Caucasian and African American Women.

摘要

Breast cancer is the most commonly occurring cancer among women. Many risk factors have been identified but a positive family history remains among the most important ones established for breast cancer. Mutations in the currently known high-risk breast cancer genes (such as BRCA1/2, etc) are common in familial breast cancer, but they can explain at best 20-25% of the overall excess familial risk and less than 5% of the total breast cancer incidence. It is most likely that residual genetic susceptibility is driven by variants at many loci, each conferring a moderately risk of the disease. A great deal of efforts has been put to identify novel moderate-risk breast cancer genes, but only a few have been identified and confirmed (3-7). Thus, there are still a great amount of unidentified risk alleles that confer susceptibility to breast cancer to be found. Some of them might be at unconventional loci (such as protein non-encoding genes) and traditionally overlooked regions (such as 3'UTR of mRNA). Differences exist between African American (AA) and Caucasian women in the incidence and nature of breast cancer (8-10). Although the breast cancer incidence rates are 20-40% higher in Caucasian women than in AA women, AA women are more likely to be diagnosed before age 50 and have aggressive diseases with poor prognosis, as characterized by a higher proportion of high-grade tumors, estrogen receptor negative (ER-)/progesterone receptor negative(PR-) tumors, compared with Caucasian women. Therefore, we hypothesize that genetic variations in miRNA genes, responsive elements in target genes and miRNA processing genes will modify breast cancer risk. To test these hypothesis we will estimate the frequencies of 35 SNPs in miRNA genes that predicted to regulate key breast cancer genes, and 22 SNPs in their responsive elements in target genes for breast cancer cases and controls.