TY - JOUR
T1 - The effects of height and BMI on prostate cancer incidence and mortality
T2 - a Mendelian randomization study in 20,848 cases and 20,214 controls from the PRACTICAL consortium
AU - Davies, Neil M
AU - Gaunt, Tom R
AU - Lewis, Sarah J
AU - Holly, Jeffrey M P
AU - Donovan, Jenny L
AU - Hamdy, Freddie C
AU - Kemp, John P
AU - Eeles, Rosalind
AU - Easton, Doug
AU - Kote-Jarai, Zsofia
AU - Al Olama, Ali Amin
AU - Benlloch, Sara
AU - Muir, Kenneth
AU - Giles, Graham G
AU - Wiklund, Fredrik
AU - Gronberg, Henrik
AU - Haiman, Christopher A
AU - Schleutker, Johanna
AU - Nordestgaard, Børge G
AU - Travis, Ruth C
AU - Neal, David
AU - Pashayan, Nora
AU - Khaw, Kay-Tee
AU - Stanford, Janet L
AU - Blot, William J
AU - Thibodeau, Stephen
AU - Maier, Christiane
AU - Kibel, Adam S
AU - Cybulski, Cezary
AU - Cannon-Albright, Lisa
AU - Brenner, Hermann
AU - Park, Jong
AU - Kaneva, Radka
AU - Batra, Jyotsna
AU - Teixeira, Manuel R
AU - Pandha, Hardev
AU - Lathrop, Mark
AU - Davey Smith, George
AU - Martin, Richard M
AU - the PRACTICAL Consortium
PY - 2015/11
Y1 - 2015/11
N2 -
Background
Epidemiological
studies suggest a potential role for obesity and determinants of adult
stature in prostate cancer risk and mortality, but the relationships
described in the literature are complex. To address uncertainty over the
causal nature of previous observational findings, we investigated
associations of height- and adiposity-related genetic variants with
prostate cancer risk and mortality.
Methods
We conducted a
case–control study based on 20,848 prostate cancers and 20,214 controls
of European ancestry from 22 studies in the PRACTICAL consortium. We
constructed genetic risk scores that summed each man’s number of height
and BMI increasing alleles across multiple single nucleotide
polymorphisms robustly associated with each phenotype from published
genome-wide association studies.
Results
The genetic risk
scores explained 6.31 and 1.46 % of the variability in height and BMI,
respectively. There was only weak evidence that genetic variants
previously associated with increased BMI were associated with a lower
prostate cancer risk (odds ratio per standard deviation increase in BMI
genetic score 0.98; 95 % CI 0.96, 1.00; p = 0.07).
Genetic variants associated with increased height were not associated
with prostate cancer incidence (OR 0.99; 95 % CI 0.97, 1.01; p = 0.23),
but were associated with an increase (OR 1.13; 95 % CI 1.08, 1.20) in
prostate cancer mortality among low-grade disease (p
heterogeneity, low vs. high grade <0.001). Genetic variants
associated with increased BMI were associated with an increase (OR 1.08;
95 % CI 1.03, 1.14) in all-cause mortality among men with low-grade
disease (p heterogeneity = 0.03).
Conclusions
We found little
evidence of a substantial effect of genetically elevated height or BMI
on prostate cancer risk, suggesting that previously reported
observational associations may reflect common environmental determinants
of height or BMI and prostate cancer risk. Genetically elevated height
and BMI were associated with increased mortality (prostate
cancer-specific and all-cause, respectively) in men with low-grade
disease, a potentially informative but novel finding that requires
replication.
AB -
Background
Epidemiological
studies suggest a potential role for obesity and determinants of adult
stature in prostate cancer risk and mortality, but the relationships
described in the literature are complex. To address uncertainty over the
causal nature of previous observational findings, we investigated
associations of height- and adiposity-related genetic variants with
prostate cancer risk and mortality.
Methods
We conducted a
case–control study based on 20,848 prostate cancers and 20,214 controls
of European ancestry from 22 studies in the PRACTICAL consortium. We
constructed genetic risk scores that summed each man’s number of height
and BMI increasing alleles across multiple single nucleotide
polymorphisms robustly associated with each phenotype from published
genome-wide association studies.
Results
The genetic risk
scores explained 6.31 and 1.46 % of the variability in height and BMI,
respectively. There was only weak evidence that genetic variants
previously associated with increased BMI were associated with a lower
prostate cancer risk (odds ratio per standard deviation increase in BMI
genetic score 0.98; 95 % CI 0.96, 1.00; p = 0.07).
Genetic variants associated with increased height were not associated
with prostate cancer incidence (OR 0.99; 95 % CI 0.97, 1.01; p = 0.23),
but were associated with an increase (OR 1.13; 95 % CI 1.08, 1.20) in
prostate cancer mortality among low-grade disease (p
heterogeneity, low vs. high grade <0.001). Genetic variants
associated with increased BMI were associated with an increase (OR 1.08;
95 % CI 1.03, 1.14) in all-cause mortality among men with low-grade
disease (p heterogeneity = 0.03).
Conclusions
We found little
evidence of a substantial effect of genetically elevated height or BMI
on prostate cancer risk, suggesting that previously reported
observational associations may reflect common environmental determinants
of height or BMI and prostate cancer risk. Genetically elevated height
and BMI were associated with increased mortality (prostate
cancer-specific and all-cause, respectively) in men with low-grade
disease, a potentially informative but novel finding that requires
replication.
KW - Height
KW - Body mass index
KW - Prostate cancer
KW - Mendelian randomization
KW - Single nucleotide polymorphisms
KW - Instrumental variables analysis
U2 - 10.1007/s10552-015-0654-9
DO - 10.1007/s10552-015-0654-9
M3 - Article (Academic Journal)
C2 - 26387087
SN - 0957-5243
VL - 26
SP - 1603
EP - 1616
JO - Cancer Causes and Control
JF - Cancer Causes and Control
ER -