Hs. Feigelson et al., Building a multigenic model of breast cancer susceptibility: CYP17 and HSD17B1 are two important candidates, CANCER RES, 61(2), 2001, pp. 785-789
We conducted a nested case-control study to evaluate whether polymorphisms
in two genes involved in estrogen metabolism, CYP17 and NSD17B1, were usefu
l in developing a breast cancer risk model that could help discriminate wom
en who are at higher risk of breast cancer, If polymorphisms in these genes
affect the level of circulating estrogens, they may directly influence bre
ast cancer risk. The base population for this study is a multiethnic cohort
study that includes African-American, Non-Latina White, Japanese, Latina,
and Native Hawaiian women, For this analysis, 1508 randomly selected contro
ls and 850 incident breast cancer cases of the first four ethnic groups who
agreed to provide a blood specimen were included (76 and 80% response rate
s, respectively). The CYP17 A2 allele and the HSD17B1 A allele were conside
red "high-risk" alleles. Subjects were then classified according to number
of high-risk alleles, After adjusting for age, weight, and ethnicity, we fo
und that carrying one or more high-risk alleles increases the risk of advan
ced breast cancer in a dose-response fashion. The risk among women carrying
four high-risk alleles was 2.21 [95% confidence interval (CI), 0.98-5.00;
P for trend = 0.03] compared with those who carried none. This risk was lar
gely limited to women who were not taking hormone replacement therapy (rela
tive risk, 2.60; 95% CI, 0.95-7.14) and was most pronounced among those wei
ghing 170 pounds or less (RR, 3.05; 95% CI, 1.29-7.25). These findings sugg
est that breast cancer risk has a strong genetic: component and supports th
e theory that the underlying mechanism of complex traits" can be understood
using a multigenic model of candidate genes.