Prostate cancer screening in men with a family history of prostate cancer: the role of partners in influencing men's screening uptake.

OBJECTIVE: To assess the role of the partners, as well as other sociodemographic and psychological factors, in influencing prostate cancer screening uptake among men with a family history of prostate cancer. METHODS: This was a cross-sectional study of 280 unaffected men with a family history of prostate cancer along with 174 of their partners, using mailed, self-administered questionnaires. RESULTS: The majority of respondents reported having had at least one prostate-specific antigen (PSA) test (78.9%) and/or one digital rectal examination (DRE) (78.0%). Ever having had a PSA test was associated with number of first- and second-degree relatives with prostate cancer (odds ratio [OR] = 1.79; 95% confidence interval [CI] 1.03 to 3.11; P = 0.040) and relationship status. Compared with men who were single, those with partners with high involvement in men's screening had a significantly higher uptake of PSA screening (OR = 3.41; 95% CI 1.12 to 10.44; P = 0.031). Ever having had a DRE was significantly and positively associated with age (OR = 1.09; 95% CI 1.05 to 1.13; P <0.001) and perceived prostate cancer risk (OR = 1.03; 95% CI 1.01 to 1.04; P <0.001), as well as having sons (OR = 2.06; 95% CI 1.06 to 3.97; P = 0.032). CONCLUSIONS: Psychological factors are the most important influence on men's uptake of DRE, whereas external factors, including partner's involvement, influence PSA uptake. If prostate cancer screening is ultimately shown to be efficacious for men with a family history of prostate cancer, screening uptake will be maximized in this target group by enlisting the support of partners.

Characterization of the breast cancer associated ATM 7271T>G (V2424G) mutation by gene expression profiling.

Mutations in ATM are responsible for the autosomal recessive disorder ataxia telangiectasia. Heterozygous mutations in ATM have been associated with an elevated risk of breast cancer. We previously reported one breast cancer family in which ATM 7271T>G (V2424G) segregated with disease, and apparently acted in a dominant negative manner. We now report the screening of 782 multiple-case breast cancer families that identified two additional index cases with ATM 7271T>G. Phylogenetic sequence analysis showed that V2424 is a highly conserved residue, and that the 2424G variant is likely to interfere with function. To elucidate the consequences of this mutation, we expression profiled wild-type, heterozygous, and homozygous lymphoblastoid cell lines (LCLs) from Scottish and Australian families using an oligonucleotide microarray. Cluster analysis revealed 77 genes that were differentially expressed in homozygous and heterozygous V2424G cells (compared to wild-type) and 11 genes differentially expressed in the homozygous cells. We also evaluated the profiles of LCLs after exposure to ionizing radiation (IR) and identified 77 genes that were differentially expressed in wild-type cells, but not in homozygous or heterozygous V2424G cells. We validated the expression differences by RT-PCR in additional heterozygous V2424G LCLs from another breast cancer family. We found no consistent cytotoxicity or abrogation of ATM kinase activity after IR in seven heterozygous V2424G LCLs, compared to wild-type LCLs, but did find an increase in the number of chromosomal aberrations. These data suggest that the V2424G missense mutation acts largely as a dominant negative in terms of the associated expression profiles.