BACKGROUND: There is a strong genetic component in prostate cancer development with an estimated heritability of 58%. In addition, recent epidemiological assessments show a familial component in prostate cancer-specific survival, which could be due to either common genetics or environment. In this study we sought to estimate the heritability of prostate cancer-specific survival by studying brothers and father-son pairs in Sweden. METHODS: We used linkage records from three Swedish national registers: the Multi-Generation Register, the Cancer Register, and the Cause of Death Register. One thousand seven hundred twenty-eight brother pairs and 6,444 father-son pairs, where both family members were diagnosed with prostate cancer, were followed for prostate cancer mortality. By assuming that (i) brothers on average share 50% of their segregating alleles and 100% environment and (ii) fathers and sons share 50% of their segregating alleles and no environment, we implemented a model including influences of additive genetics (heritability), shared environment and non-shared environment for survival data. A conditional likelihood estimation procedure was developed to fit the model. Data simulation was applied to validate model assumptions. RESULTS: In a model that adjusted for age at diagnosis and calendar period, the estimated heritability of prostate cancer-specific survival was 0.10 (95% CI = 0.00-0.20) that was borderline significantly different from zero (P = 0.057). The shared environment component was not significantly different from zero with a point estimate of 0.00 (95% CI = 0.00-0.13). Simulation studies and sensitivity analysis revealed that the estimated heritability component was robust, whereas the shared environmental component may be underestimated. CONCLUSIONS: Heritability of prostate cancer-specific survival is considerably lower than for prostate cancer incidence. This supports a hypothesis that susceptibility of disease and progression of disease are separate mechanisms that involve different genes. Further assessment of the genetic basis of prostate cancer-specific survival is warranted. Prostate 77:900-907, 2017.
BACKGROUND: There is a strong genetic component in prostate cancer development with an estimated heritability of 58%. In addition, recent epidemiological assessments show a familial component in prostate cancer-specific survival, which could be due to either common genetics or environment. In this study we sought to estimate the heritability of prostate cancer-specific survival by studying brothers and father-son pairs in Sweden. METHODS: We used linkage records from three Swedish national registers: the Multi-Generation Register, the Cancer Register, and the Cause of Death Register. One thousand seven hundred twenty-eight brother pairs and 6,444 father-son pairs, where both family members were diagnosed with prostate cancer, were followed for prostate cancer mortality. By assuming that (i) brothers on average share 50% of their segregating alleles and 100% environment and (ii) fathers and sons share 50% of their segregating alleles and no environment, we implemented a model including influences of additive genetics (heritability), shared environment and non-shared environment for survival data. A conditional likelihood estimation procedure was developed to fit the model. Data simulation was applied to validate model assumptions. RESULTS: In a model that adjusted for age at diagnosis and calendar period, the estimated heritability of prostate cancer-specific survival was 0.10 (95% CI = 0.00-0.20) that was borderline significantly different from zero (P = 0.057). The shared environment component was not significantly different from zero with a point estimate of 0.00 (95% CI = 0.00-0.13). Simulation studies and sensitivity analysis revealed that the estimated heritability component was robust, whereas the shared environmental component may be underestimated. CONCLUSIONS: Heritability of prostate cancer-specific survival is considerably lower than for prostate cancer incidence. This supports a hypothesis that susceptibility of disease and progression of disease are separate mechanisms that involve different genes. Further assessment of the genetic basis of prostate cancer-specific survival is warranted. Prostate 77:900-907, 2017.
Authors: Gudrun Wahlström; Samuel Heron; Matias Knuuttila; Elina Kaikkonen; Nea Tulonen; Olli Metsälä; Christoffer Löf; Otto Ettala; Peter J Boström; Pekka Taimen; Matti Poutanen; Johanna Schleutker Journal: Hum Mol Genet Date: 2022-06-22 Impact factor: 5.121