Pubertal development and prostate cancer risk: Mendelian randomization study in a population-based cohort
Martin RM; Cybulski C; Bonilla C; Eeles R; Khaw KT; Stanford JL; Park J; Wiklund F; Nordestgaard BG; Kote-Jarai Z; Lathrop M; Easton D; Muir K; Thibodeau S; Smith GD; Donovan JL; Pandha H; Batra J; Haiman CA; Giles GG; Kaneva R; Hamdy FC; Blot WJ; Benlloch S; Kibel AS; Brenner H; Al Olama AA; Travis RC; Teixeira MR; Schleutker J; Gronberg H; Neal DE; Pashayan N; Lewis SJ; Maier C; Cannon-Albright L
Pubertal development and prostate cancer risk: Mendelian randomization study in a population-based cohort
Martin RM
Cybulski C
Bonilla C
Eeles R
Khaw KT
Stanford JL
Park J
Wiklund F
Nordestgaard BG
Kote-Jarai Z
Lathrop M
Easton D
Muir K
Thibodeau S
Smith GD
Donovan JL
Pandha H
Batra J
Haiman CA
Giles GG
Kaneva R
Hamdy FC
Blot WJ
Benlloch S
Kibel AS
Brenner H
Al Olama AA
Travis RC
Teixeira MR
Schleutker J
Gronberg H
Neal DE
Pashayan N
Lewis SJ
Maier C
Cannon-Albright L
BIOMED CENTRAL LTD
Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2021042715758
https://urn.fi/URN:NBN:fi-fe2021042715758
Tiivistelmä
Background: Epidemiological studies have observed a positive association between an earlier age at sexual development and prostate cancer, but markers of sexual maturation in boys are imprecise and observational estimates are likely to suffer from a degree of uncontrolled confounding. To obtain causal estimates, we examined the role of pubertal development in prostate cancer using genetic polymorphisms associated with Tanner stage in adolescent boys in a Mendelian randomization (MR) approach.Methods: We derived a weighted genetic risk score for pubertal development, combining 13 SNPs associated with male Tanner stage. A higher score indicated a later puberty onset. We examined the association of this score with prostate cancer risk, stage and grade in the UK-based ProtecT case-control study (n = 2,927), and used the PRACTICAL consortium (n = 43,737) as a replication sample.Results: In ProtecT, the puberty genetic score was inversely associated with prostate cancer grade (odds ratio (OR) of high-vs. low-grade cancer, per tertile of the score: 0.76; 95 % CI, 0.64-0.89). In an instrumental variable estimation of the causal OR, later physical development in adolescence (equivalent to a difference of one Tanner stage between pubertal boys of the same age) was associated with a 77 % (95 % CI, 43-91 %) reduced odds of high Gleason prostate cancer. In PRACTICAL, the puberty genetic score was associated with prostate cancer stage (OR of advanced vs. localized cancer, per tertile: 0.95; 95 % CI, 0.91-1.00) and prostate cancer-specific mortality (hazard ratio amongst cases, per tertile: 0.94; 95 % CI, 0.90-0.98), but not with disease grade.Conclusions: Older age at sexual maturation is causally linked to a reduced risk of later prostate cancer, especially aggressive disease.
Kokoelmat
- Rinnakkaistallenteet [19207]