Participants who had withdrawn their consent, had been diagnosed with cancer before baseline, failed to be genotyped, reported a mismatch sex with genetic data, or with missing data on Phenotypic …
Cox proportional hazards regression adjusted for age, height, cancer family history, Townsend deprivation index at recruitment, and the first 10 principal components of ancestry. Error bars are 95% …
The distribution of PhenoAgeAccel between participants with incident cancer and those without incident cancer in the UK Biobank for men(A) and women (B). Participants in the UK Biobank were divided …
The hazard ratios (HRs) were estimated using Cox proportional hazard models with adjustment for age, height, family history of cancer, Townsend deprivation index, and the first 10 principal …
The hazard ratios (HRs) were estimated using Cox proportional hazard models with adjustment for age, height, family history of cancer, Townsend deprivation index, and the first 10 principal …
The x-axis is chronological age. The curves describe the average risk of participants in younger and older Phenotypic Age (PhenoAge) groups. The dashed curve represents the average risk of the whole …
Men (n=173,431) | Women (n=201,032) | |||
---|---|---|---|---|
Biologically younger n=81,242 | Biologically older n=92,189 | Biologically younger n=123,648 | Biologically older n=77,384 | |
PhenoAgeAccel, median (IQR), years | –2.61 (−4.35–-1.25) | 3.28 (1.50–6.06) | –3.55 (−5.64–-1.81) | 3.07 (1.33–5.79) |
Age at baseline, median (IQR), years | 57.00 (49.00–62.00) | 58.00 (50.00–64.00) | 58.00 (51.00–63.00) | 56.00 (48.00–62.00) |
Height, median (IQR), centimeters | 176.00 (171.00–181.00) | 175.00 (171.00–180.00) | 162.50 (158.00–167.00) | 162.00 (158.00–166.50) |
Townsend deprivation index, median (IQR) | –2.34 (−3.76–0.16) | –1.86 (−3.52–1.10) | –2.33 (−3.73–0.07) | –1.79 (−3.44–1.10) |
Family history of cancer, n (%) | ||||
No | 53907 (66.35) | 60654 (65.79) | 79800 (64.54) | 50924 (65.81) |
Yes | 27335 (33.65) | 31535 (34.21) | 43848 (35.46) | 26460 (34.19) |
Healthy lifestyle factors, n (%) | ||||
No current smoking | 46412 (57.13) | 43216 (46.88) | 78743 (63.68) | 45416 (58.69) |
No alcohol consumption | 2064 (2.54) | 2828 (3.07) | 6221 (5.03) | 5459 (7.05) |
Normal BMI | 66120 (81.39) | 62654 (67.96) | 103054 (83.34) | 49003 (63.32) |
Regular physical activity | 54346 (66.89) | 57733 (62.62) | 80629 (65.21) | 46468 (60.05) |
Healthy diet | 18540 (22.82) | 15486 (16.80) | 39547 (31.98) | 19826 (25.62) |
Healthy lifestyle*, n (%) | ||||
Favorable | 7781 (9.58) | 5255 (5.70) | 17781 (14.38) | 7178 (9.28) |
Intermediate | 57683 (71.00) | 57489 (62.36) | 87272 (70.58) | 49324 (63.74) |
Unfavorable | 15778 (19.42) | 29445 (31.94) | 18595 (15.04) | 20882 (26.98) |
Albumin, median (IQR), (g/L) | 46.20 (44.62–47.85) | 44.95 (43.28–46.64) | 45.47 (43.87–47.12) | 44.04 (42.42–45.70) |
Alkaline phosphatase, median (IQR), (U/L) | 75.00 (64.30–87.40) | 82.80 (70.10–97.90) | 78.70 (65.10–93.90) | 86.20 (70.60–104.00) |
Creatinine, median (IQR), (umol/L) | 77.60 (70.90–84.70) | 82.50 (74.40–91.60) | 61.70 (56.00–67.90) | 65.50 (58.90–73.20) |
Glucose, median (IQR), (mmol/l) | 4.82 (4.49–5.14) | 5.09 (4.72–5.60) | 4.84 (4.54–5.14) | 5.05 (4.70–5.55) |
C-reactive protein, median (IQR), (mg/dL) | 0.09 (0.05–0.16) | 0.19 (0.10–0.36) | 0.10 (0.05–0.20) | 0.25 (0.12–0.51) |
Lymphocyte percent, median (IQR), (%) | 29.86 (25.48–34.48) | 25.60 (21.22–30.24) | 31.09 (26.58–35.80) | 27.00 (22.62–31.61) |
Mean cell volume, median (IQR), (fL) | 90.90 (88.46–93.30) | 91.90 (89.10–94.74) | 91.10 (88.60–93.54) | 90.98 (87.64–94.02) |
Red cell distribution width, median (IQR), (%) | 13.01 (12.70–13.37) | 13.63 (13.21–14.11) | 13.10 (12.71–13.50) | 13.90 (13.40–14.55) |
White blood cell count, median (IQR), (1000 cells/uL) | 6.12 (5.29–7.10) | 7.27 (6.17–8.51) | 6.24 (5.37–7.26) | 7.41 (6.30–8.73) |
Healthy lifestyle was defined as favorable (4–5 healthy lifestyle factors), intermediate (2–3 healthy lifestyle factors), and unfavorable (0–1 healthy lifestyle factor).
Model 1* | Model 2† | ||||||
---|---|---|---|---|---|---|---|
n (cases) | Person-Years | HR (95% CI) | p value | HR (95% CI) | value | ||
Men | Per 5 years increase | 173431 (11532) | 1190628 | 1.15 (1.13–1.17) | 1.55×10–54 | 1.13 (1.11–1.15) | 5.46×10–44 |
Category | |||||||
Biologically younger | 81242 (4649) | 564818 | Ref. | Ref. | |||
Biologically older | 92189 (6883) | 625810 | 1.22 (1.18–1.27) | 5.31×10–26 | 1.19 (1.15–1.24) | 3.18×10–20 | |
Quintiles† | |||||||
Low | 34687 (1864) | 242519 | Ref. | Ref. | |||
Intermediate | 104058 (6668) | 716312 | 1.15 (1.09–1.21) | 2.17×10–7 | 1.12 (1.07–1.18) | 8.01×10–6 | |
High | 34686 (3000) | 231797 | 1.44 (1.36–1.53) | 1.01×10–34 | 1.39 (1.31–1.47) | 1.99×10–27 | |
p for trend | 3.03×10–37 | 1.65×10–29 | |||||
Women | Per 5 years increase | 201032 (10838) | 1393562 | 1.15 (1.13–1.17) | 1.80×10–53 | 1.13 (1.11–1.15) | 1.35×10–41 |
Category | |||||||
Biologically younger | 123648 (6229) | 861570 | Ref. | Ref. | |||
Biologically older | 77384 (4609) | 531993 | 1.26 (1.22–1.31) | 5.91×10–33 | 1.23 (1.18–1.28) | 2.71×10–25 | |
Quintiles‡ | |||||||
Low | 40207 (1946) | 281912 | Ref. | Ref. | |||
Intermediate | 120618 (6351) | 836341 | 1.15 (1.09–1.21) | 1.46×10–7 | 1.13 (1.07–1.18) | 5.89×10–6 | |
High | 40207 (2541) | 275309 | 1.46 (1.38–1.55) | 2.54×10–36 | 1.40 (1.32–1.49) | 5.94×10–28 | |
p for trend | 4.23×10–37 | 1.36×10–28 |
Cox proportional hazards regression adjusted for Model 1, as well as cancer polygenic risk score and healthy lifestyle.
Defined by quintiles of PhenoAgeAccel: low (the bottom quintile), intermediate (quintiles 2–4), and high (the top quintile).
Cox proportional hazards regression adjusted for age, height, cancer family history, Townsend deprivation index at recruitment, and the first 10 principal components of ancestry.
CI, confidence interval; HR, hazards ratio; Ref, reference.
Gender | PhenoAgeAccel category | Low genetic risk | Intermediate genetic risk | High genetic risk | |||||
---|---|---|---|---|---|---|---|---|---|
Biologically younger | Biologically older | Biologically younger | Biologically older | Biologically younger | Biologically older | ||||
Men | No. of cases/Person years | 668/114962 | 1031/124526 | 2606/338950 | 4012/376782 | 1375/110907 | 1840/124502 | ||
Hazards ratio | Ref. | 1.29 (1.17–1.42) | Ref. | 1.27 (1.21–1.33) | Ref. | 1.10 (1.02–1.18) | |||
(95% CI) | |||||||||
p value | 3.53×10–7 | 3.15×10–21 | 1.07×10–2 | ||||||
Absolute risk (%)- 5 years (95% CI) | 2.71 (2.49–2.94) | 3.87 (3.60–4.14) | 3.57 (3.41–3.72) | 4.95 (4.78–5.13) | 5.78 (5.44–6.11) | 6.90 (6.55–7.26) | |||
Absolute risk increase (%)- 5 years (95% CI) | Ref. | 1.16 (0.84–1.46) | Ref. | 1.39 (1.19–1.60) | Ref. | 1.13 (0.68–1.52) | |||
Women | No. of cases/Person years | 1030/173195 | 761/106937 | 3579/518611 | 2704/318753 | 1620/169764 | 1144/106303 | ||
Hazards ratio | Ref. | 1.25 (1.14–1.38) | Ref. | 1.30 (1.24–1.37) | Ref. | 1.19 (1.10–1.28) | |||
(95% CI) | |||||||||
p value | 2.65×10–6 | 1.84×10–24 | 8.19×10–6 | ||||||
Absolute risk (%) - 5 years (95% CI) | 2.83 (2.63–3.02) | 3.39 (3.12–3.65) | 3.27 (3.15–3.39) | 4.02 (3.86–4.19) | 4.58 (4.33–4.83) | 5.17 (4.84–5.49) | |||
Absolute risk increase (%)- 5 years (95% CI) | Ref. | 0.56 (0.26–0.86) | Ref. | 0.76 (0.57–0.93) | Ref. | 0.59 (0.23–0.98) |
Cox proportional hazards regression is adjusted for age, height, family history of cancer, Townsend deprivation index, height, and the first 10 principal components of ancestry.
CI, confidence interval; Ref, reference.
Supplementary Tables a - k for additional results.
(a) Association results of Phenotypic Age Acceleration (PhenoAgeAccel) with site-specific cancer risk per 5 years increased. (b) Sensitivity analysis of association between different risk levels of PhenoAgeAccel and cancer risk. (c) Sensitivity analysis of association between PhenoAgeAccel and cancer risk by excluding of patients diagnosed in the first two follow-ups. (d) Sensitivity analysis of association between PhenoAgeAccel and cancer risk in unimputed data. (e) Sensitivity analysis of association between PhenoAgeAccel and cancer risk in the unrelated white British population. (f) Sensitivity analysis of association between PhenoAgeAccel and cancer risk using retrained PhenoAge in cancer-free participants. (g) Relative excess risk due to interaction (RERI) and attributable proportion (AP) for additive interaction between genetic and PhenoAgeAccel categories. (h) Risk of incident cancer according to PhenoAgeAccel categories within each genetic risk level. (i) PhenoAgeAccel of participants stratified by lifestyle factors. (j) Association results of PhenoAgeAccel with lifestyle factors of participants. (k) RERI and AP for additive interaction between genetic and lifestyle factors on PhenoAgeAccel.