Research Frontier Polygenic risk scores combined with family history of cancer are more conducive to identifying people at high risk of death from prostate cancer

A total of 10,120 men were included in the study, and the median age at the start of the study was 65.
3 years
.
Among them, 2557 men had a family history of prostate cancer or breast cancer (49.
9% had a family history of prostate cancer only, 42.
4% had a family history of breast cancer alone, and 7.
7% had both family history).

Men with a family history had higher PRS scores and a higher proportion of previous prostate-specific antigen (PSA) tests, with similar baseline data for other studies (Table 1).

Table 1 Baseline data at the beginning of follow-up

A total of 1915 cases of prostate cancer (median follow-up 18.
3 years, IQR 11.
1-22.
8 years) and 166 fatal prostate cancer events (median follow-up 23.
2 years, IQR 13.
8-25.
0 years)
were observed during study follow-up 。 Consistent with previous reports, family history of cancer was associated with increased incidence of prostate cancer, with an HR of 1.
24 (95% CI 1.
06 to 1.
44) with only a family history of breast cancer, 1.
58 (95% CI 1.
38 to 1.
81) with only a family history of prostate cancer, and an HR of 1.
65 (95% CI 1.
21 to 2.
24)
for both.
The analysis of prostate cancer-specific death was similar (Table 2).

High-risk men (top 25% PRS score and family history) had the highest incidence of prostate cancer compared with low-risk men (low PRS score and no family history), HR = 6.
95 (95% CI 5.
57 to 8.
66); HR for prostate cancer-specific death was 4.
84 (95% CI 2.
59 to 9.
03)

Table 2 Analysis of the association between family history of cancer and PRS score of prostate cancer and prostate cancer incidence and specific mortality

Men with a family history of prostate or breast cancer have a higher absolute risk of developing prostate or prostate cancer-specific death, regardless of PRS score than those without a family history (Figure 1).

Among men in the top 25% of PRS scores, the lifetime risk of prostate cancer death was 3.
2% (95% CI 1.
9% to 5.
2%) in men with a family history and 1.
8% (95% CI 1.
2% to 2.
7%)
in men without a family history.
Among men with the lowest PRS scores, the lifetime risk of death from prostate cancer was 1.
2% (95% CI 0.
5% to 2.
9%) for men with a family history and 0.
4% (95% CI 0.
1% to 0.
8%)
for men without a family history.

Fig.
1 The absolute risk of prostate cancer or prostate-specific death in men with a family history of cancer at different PRS levels

In addition, most events occurred in men with high PRS scores (50% to 100%) and a family history of cancer (Figure 2).

Fig.
2 Occurrence of prostate cancer and prostate-specific death

In addition, patients with a high PRS score (50%-100%) and a family history of prostate cancer or breast cancer (61.
8% of the total) accounted for 100% of prostate cancer-specific deaths before the age of 70 years; accounted for 97.
5% of prostate cancer-specific deaths before the age of 75; accounted for 94.
4% of prostate cancer-specific deaths before the age of 80 years; It accounted for 89.
4% of prostate cancer-specific deaths before the age of 85.