Environment plus genotype may best predict prostate cancer outcomes
MedWire News: Genetic risk factors may best be able to predict poor outcomes in prostate cancer patients when socioeconomic and lifestyle factors are also taken into account, report US researchers.
Timothy Rebbeck, from University of Pennsylvania School of Medicine in Philadelphia, and colleagues report that genotypes alone could not predict time to biochemical failure in a cohort of post-radical prostatectomy patients.
However, when the macroenvironmental circumstances of men carrying two genetic loci known to be linked to prostate cancer outcomes were considered, they showed a significantly increased risk for biochemical failure.
Among the 444 White patients studied, 11% experienced biochemical failure (defined as a postsurgical prostate-specific antigen level of more than 0.2 ng/ml) after a median of 22.5 months.
The researchers matched the men's residential addresses with US census (2000) data in order to quantify macroenvironmental status including: aging and social isolation; education; neighborhood housing quality; and socioeconomic status.
Rebbeck and team tested the joint effects on time to biochemical failure of 86 previously identified genotypes together with the above data. All analyses were adjusted for age at diagnosis and tumor aggressiveness (nonaggressive cancer=stage I-II, Gleason score <7).
For every 1% increase above the neighborhood norm, the factors most significantly associated with a shorter time to biochemical failure were the percentage of residents aged 65 years or older (hazard ratio [HR]=1.02), the percentage of vacant housing (HR=1.28), and the percentage of unemployed individuals aged 16 years or older (HR=1.08).
No individual gene loci showed any association with time to biochemical failure in the cohort, observe the researchers.
However, for each percentage increase in the proportion of neighborhood household heads aged 65 years or higher, there was a 10% decrease in time to biochemical failure among men who carried the TT genotype at locus MSMB rs10993994, compared with men who carried any other genotype.
Furthermore, men who carried the TT genotype at HNF1/TCF2 rs 4430796 had a 3% decrease in time to biochemical failure for every US$1000 increase in neighborhood per capita income, whereas this was associated with a 7% increase in time to biochemical failure for men who carried the CC genotype.
"The present results might provide information that moves research in these areas away from more misclassified variables (eg, race), and point toward specific areas in which targeted interventions might be developed to reduce disparities," conclude Rebbeck et al in the journal Cancer Epidemiology Biomarkers and Prevention.
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By Sarah Guy