Suchergebnisse

SummaryDepot medroxyprogesterone acetate (DMPA) was approved as an investigational new drug for contraceptive use in the United States between 1967 and 1978. Patterns of contraceptive choice and changing methods were determined among 36,298 women attending a family planning clinic between 1967 and 1976. This population was the largest concentration of US women who had DMPA available as a contraceptive option. By 1974, women in the age group 35–49 were as likely to choose DMPA as either oral contraception or an intrauterine device. Coincidentally, use of the most popular choice, oral contraception, declined in older women and IUD use dropped sharply in all age groups. On average, users of DMPA were more likely to continue their method than were users of IUDs or barrier methods. Among women in the 35–49 age group, DMPA users were the group least likely to change methods.

Recent Genome-Wide Association Studies (GWAS) have identified four low-penetrance ovarian cancer susceptibility loci. We hypothesized that further moderate- or low-penetrance variants exist among the subset of single-nucleotide polymorphisms (SNPs) not well tagged by the genotyping arrays used in the previous studies, which would account for some of the remaining risk. We therefore conducted a time- and cost-effective stage 1 GWAS on 342 invasive serous cases and 643 controls genotyped on pooled DNA using the high-density Illumina 1M-Duo array. We followed up 20 of the most significantly associated SNPs, which are not well tagged by the lower density arrays used by the published GWAS, and genotyping them on individual DNA. Most of the top 20 SNPs were clearly validated by individually genotyping the samples used in the pools. However, none of the 20 SNPs replicated when tested for association in a much larger stage 2 set of 4,651 cases and 6,966 controls from the Ovarian Cancer Association Consortium. Given that most of the top 20 SNPs from pooling were validated in the same samples by individual genotyping, the lack of replication is likely to be due to the relatively small sample size in our stage 1 GWAS rather than due to problems with the pooling approach. We conclude that there are unlikely to be any moderate or large effects on ovarian cancer risk untagged by less dense arrays. However, our study lacked power to make clear statements on the existence of hitherto untagged small-effect variants.