Περίληψη:
Steroid hormones are believed to play an important role in prostate
carcinogenesis, but epidemiological evidence linking prostate cancer and
steroid hormone genes has been inconclusive, in part due to small sample
sizes or incomplete characterization of genetic variation at the locus
of interest. Here we report on the results of a comprehensive study of
the association between HSD17B1 and prostate cancer by the Breast and
Prostate Cancer Cohort Consortium, a large collaborative study. HSD17B1
encodes 17p-hydroxysteroid clehydrogenase 1, an enzyme that converts
clihydroepiandrosterone to the testosterone precursor Delta
5-androsterone-3 beta, 17 beta-diol and converts estrone to estradiol.
The Breast and Prostate Cancer Cohort Consortium researchers
systematically characterized variation in HSD17B1 by targeted
resequencing and dense genotyping; selected haplotype-tagging single
nucleotide polymorphisms (htSNPs) that efficiently predict common
variants in U.S. and European whites, Latinos, Japanese Americans, and
Native Hawaiians; and genotyped these htSNPs in 8,290 prostate cancer
cases and 9,367 study-, age-, and ethnicity-matched controls. We found
no evidence that HSD17B1 htSNPs (including the nonsynonymous coding SNP
S312G) or htSNP haplotypes were associated with risk of prostate cancer
or tumor stage in the pooled multiethnic sample or in U.S. and European
whites. Analyses stratified by age, body mass index, and family history
of disease found no subgroup-specific associations between these HSD17B1
htSNPs and prostate cancer. We found significant evidence of
heterogeneity in associations between HSD17B1 haplotypes and prostate
cancer across ethnicity: one haplotype had a significant (p < 0.002)
inverse association with risk of prostate cancer in Latinos and Japanese
Americans but showed no evidence of association in African Americans,
Native Hawaiians, or whites. However, the smaller numbers of Latinos and
Japanese Americans in this study makes these subgroup analyses less
reliable. These results suggest that the germline variants in HSD17B1
characterized by these htSNPs do not substantially influence the risk of
prostate cancer in U.S. and European whites.
Συγγραφείς:
Kraft, P
Pharoah, P
Chanock, SJ
Albanes, D
Kolonel, LN
and Hayes, RB
Altshuler, D
Andriole, G
Berg, C
Boeing, H
and Burtt, NP
Bueno-de-Mesquita, B
Calle, EE
Cann, H and
Canzian, F
Chen, YC
Crawford, DE
Dunning, AM
Feigelson,
HS
Freedman, ML
Gaziano, JM
Giovannucci, E
Gonzalez, CA
and Haiman, CA
Hallmans, G
Henderson, BE
Hirschhorn, JN and
Hunter, DJ
Kaaks, R
Key, T
Le Marchand, L
Ma, J and
Overvad, K
Palli, D
Pike, MC
Riboli, E
Rodriguez, C and
Setiawan, WV
Stampfer, MJ
Stram, DO
Thomas, G
Thun, MJ
and Travis, R
Trichopoulou, A
Virtamo, J
Wacholder, S
