RESUMO
We conducted an association study to identify risk variants for familial prostate cancer within the HPCX locus at Xq27 among Americans of Northern European descent. We investigated a total of 507 familial prostate cancer probands and 507 age-matched controls without a personal or family history of prostate cancer. The study population was subdivided into a set of training subjects to explore genetic variation of the locus potentially impacting risk of prostate cancer, and an independent set of test subjects to confirm the association and to assign significance, addressing multiple comparisons. We identified a 22.9 kb haplotype nominally associated with prostate cancer among training subjects (292 cases, 292 controls; chi(2) = 5.08, P = 0.020), that was confirmed among test subjects (215 cases, 215 controls; chi(2) = 3.73, P = 0.040). The haplotype predisposed to prostate cancer with an odds ratio of 3.41 (95% CI 1.04-11.17, P = 0.034) among test subjects. The haplotype extending from rs5907859 to rs1493189 is concordant with a prior study of the region within the Finnish founder population, and warrants further independent investigation.
Assuntos
Cromossomos Humanos X/genética , Neoplasias da Próstata/genética , Estudos de Casos e Controles , Predisposição Genética para Doença , Variação Genética , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Estados Unidos , População Branca/genéticaRESUMO
We conducted a genome-wide SNP association study on prostate cancer on over 23,000 Icelanders, followed by a replication study including over 15,500 individuals from Europe and the United States. Two newly identified variants were shown to be associated with prostate cancer: rs5945572 on Xp11.22 and rs721048 on 2p15 (odds ratios (OR) = 1.23 and 1.15; P = 3.9 x 10(-13) and 7.7 x 10(-9), respectively). The 2p15 variant shows a significantly stronger association with more aggressive, rather than less aggressive, forms of the disease.
Assuntos
Cromossomos Humanos Par 2 , Cromossomos Humanos X , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/genética , Estudos de Casos e Controles , Frequência do Gene , Testes Genéticos , Humanos , Islândia , Desequilíbrio de Ligação , Masculino , Países Baixos , Espanha , Suécia , Estados UnidosRESUMO
The CYP11A1 gene encodes the cholesterol side chain cleavage enzyme that catalyzes the initial and rate-limiting step of steroidogenesis. A large number of epidemiologic studies have implicated the duration and degree of endogenous estrogen exposure in the development of breast cancer in women. Here, we conduct a systematic investigation of the role of genetic variation of the CYP11A1 gene in breast cancer risk in a study of 1193 breast cancer cases and 1310 matched controls from the Shanghai Breast Cancer Study. We characterize the genetic architecture of the CYP11A1 gene in a Chinese study population. We then genotype tagging polymorphisms to capture common variation at the locus for tests of association. Variants designating a haplotype encompassing the gene promoter are significantly associated with both increased expression (P = 1.6e-6) and increased breast cancer risk: heterozygote age-adjusted odds ratio (OR), 1.51 [95% confidence interval (95% CI), 1.19-1.91]; homozygote age-adjusted OR, 2.94 (95% CI, 1.22-7.12), test for trend, P = 5.0e-5. Among genes controlling endogenous estrogen metabolism, CYP11A1 harbors common variants that may influence expression to significantly modify risk of breast cancer.