Περίληψη:
The 17 beta-hydroxysteroid dehydrogenase 1 gene (HSD17B1) encodes
17HSD1, which catalyzes the final step of estradiol biosynthesis.
Despite the important role of HSD17B1 in hormone metabolism, few
epidemiologic studies of HSD17B1 and breast cancer have been conducted.
This study includes 5,370 breast cancer cases and 7,480 matched controls
from five large cohorts in the Breast and Prostate Cancer Cohort
Consortium. We characterized variation in HSD17B1 by resequencing and
dense genotyping a multiethnic sample and identified haplotype-tagging
single nucleotide polymorphisms (htSNP) that capture common variation
within a 33.3-kb region around HSD17B1. Four htSNPs, including the
previously studied SNP rs605059 (S312G), were genotyped to tag five
common haplotypes in all cases and controls. Conditional logistic
regression was used to estimate odds ratios (OR) for disease. We found
no evidence of association between common HSD17B1 haplotypes or htSNPs
and overall risk of breast cancer. The OR for each haplotype relative to
the most common haplotype ranged from 0.98 to 1.07 (omnibus test for
association: X-2 = 3.77, P = 0.58, 5 degrees of freedom). When cases
were subdivided by estrogen receptor (ER) status, two common haplotypes
were associated with ER-negative tumors (test for trend, Ps = 0.0009 and
0.0076; n = 353 cases). HSD17B1 variants that are common in Caucasians
are not associated with overall risk of breast cancer; however, there
was an association among the subset of ER-negative tumors. Although the
probability that these ER-negative findings are false-positive results
is high, these findings were consistent across each cohort examined and
warrant further study.
Συγγραφείς:
Feigelson, HS
Cox, DG
Cann, HM
Wacholder, S
Kaaks, R and
Henderson, BE
Albanes, D
Altshuler, D
Berglund, G and
Berrino, F
Bingham, S
Buring, JE
Burtt, NP
Calle, EE and
Chanock, SJ
Clavel-Chapelon, F
Colditz, G
Diver, WR and
Freedman, ML
Haiman, CA
Hankinson, SE
Hayes, RB and
Hirschhorn, JN
Hunter, D
Kolonel, LN
Kraft, P and
LeMarchand, L
Linseisen, J
Modi, W
Navarro, C
Peeters,
PH
Pike, MC
Riboli, E
Setiawan, VW
Stram, DO
Thomas,
G
Thun, MJ
Tjonneland, A
Trichopoulos, D
