C-reactive protein-associated genetic variants and cancer risk: findings from FINRISK 1992, FINRISK 1997 and Health 2000 studies.
BACKGROUND
Evidence from prospective observational studies suggests that elevated circulating C-reactive protein (CRP) concentrations are associated with cancer risk, but it is unclear whether this association is causal. In order to examine this, we investigated whether genetic variants that are associated with circulating CRP concentrations are associated with cancer risk.


METHODS
We pooled data from three population-based prospective Finnish studies: FINRISK 1992 (n = 5289), FINRISK 1997 (n = 7160) and Health 2000 (n = 6299). Cancer cases were identified from cancer registrations. Thirteen CRP-associated SNPs, identified from genome-wide association studies, were genotyped. We examined the associations of the SNPs and cancer risk using Cox, probit and instrumented probit regression models.


RESULTS
Compared to common allele homozygotes, individuals carrying one or two variant T alleles at rs1892534 had 1.05-fold (95% confidence interval (CI): 0.90, 1.23) and 1.2-fold (95% CI: 1.01, 1.42) increased overall cancer risk, respectively. Individuals with one or two variant A alleles at rs1169300 or rs2464196 had approximately 1.5- and 2-fold increased risk of lung cancer, respectively (p trend for both: 0.007). CRP SNPs were not associated with colorectal, prostate or breast cancer risk nor was CRP-associated with the probability of developing cancer in the instrumented probit analyses.


CONCLUSIONS
We found some evidence for an association of a small number of CRP-associated SNPs with the overall cancer risk and lung cancer risk. Our instrumental variable analyses provided no clear evidence for a causal association of CRP and cancer. These findings suggest that circulating CRP concentrations are unlikely to have a causal role in cancer.
Heikkilä
Katriina
K
The National Institute for Health and Welfare, Helsinki, Finland. katriina.heikkila@npeu.ox.ac.uk
Silander
Kaisa
K
Salomaa
Veikko
V
Jousilahti
Pekka
P
Koskinen
Seppo
S
Pukkala
Eero
E
Perola
Markus
M
D000328:Adult; D000368:Aged; D002097:C-Reactive Protein / Q000235:genetics*; D005260:Female; D005387:Finland / Q000453:epidemiology; D006580:Genetic Carrier Screening; D005819:Genetic Markers; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012042:Registries; D012307:Risk Factors
D005819:Genetic Markers; D002097:C-Reactive Protein