BRCA1 and BRCA2 mutations in women from Shanghai China.

Little is known about the frequency of germ-line mutations in the breast cancer susceptibility genes BRCA1 and BRCA2 among Asian populations. We investigated the distribution of BRCA1 and BRCA2 germ-line mutations and polymorphisms in a cohort of women from Shanghai, China. Study subjects totaled 1306, and included 645 women with breast cancer, 342 women with benign breast disease, and 319 unaffected controls, born between 1924 and 1958, selected from women enrolled in a randomized trial of Breast Self-Examination in Shanghai, China. Women were selected without regard to family history of breast or ovarian cancer. All of the coding regions and exon-intron boundaries were screened. Data were analyzed with respect to age at diagnosis, and family history of breast and ovarian cancer. The prevalence of known disease-associated mutations in women with breast cancer was 1.1% each, for BRCA1 and BRCA2. Among breast cancer cases with a family history of breast or ovarian cancer, 8.1% and 2.7% carried likely BRCA1 and BRCA2 disease-associated mutations, respectively. Overall, these results suggest that inherited susceptibility to breast cancer due to germ-line BRCA1/2 mutations among women with a family history of breast cancer is comparable between women from Shanghai and Caucasian women of Western European descent. Most alterations observed appear unique to the Chinese population, suggesting a resource that will be useful for assessing risk among both Chinese women and United States women of Chinese descent.

Association of HPC2/ELAC2 polymorphisms with risk of prostate cancer in a population-based study.

Genetic polymorphism in HPC2/ELAC2 was recently associated with risk of sporadic prostate cancer. To determine the contribution of two HPC2/ELAC2 missense variants (Ser217Leu and Ala541Thr) to the risk of developing prostate cancer, we conducted a population-based case-control study of middle-aged men (40-64 years). Cases (n=591) were ascertained from the Seattle-Puget Sound Surveillance, Epidemiology, and End Results Cancer Registry and Controls (n=538) from the same general population were identified through random-digit dialing. Subjects were residents of King County, Washington, and were frequency matched on age. Cases (32%) had a slightly higher frequency of the Leu217 variant compared with controls (29%), but there were no differences in the frequency of the Thr541 allele (4%). When considering joint genotypes, white men homozygous for the Leu217 variant on an Ala541/Ala541 background had an increased risk of prostate cancer [odds ratio (OR)=1.84; 95% confidence interval (CI), 1.11-3.06]. Different risk profiles were also observed when cases were stratified by disease aggressiveness. Men with at least one Leu217 allele had an elevated risk (OR=1.34; 95% CI, 1.02-1.76) of less aggressive prostate cancer (localized stage and Gleason score < or = 7), with a stronger association among men with two Leu217 alleles (OR=1.73; 95% CI, 1.08-2.77). The Ala541Thr polymorphism was not associated with risk, and neither variant was associated with more aggressive prostate cancer phenotypes. We estimate that the Ser217Leu genotype may account for approximately 14% of less aggressive prostate cancer cases and 9% of all sporadic cases in the general United States population of white men