According to the latest Global Cancer Statistics Report, global cancer incidence is increasing rapidly, with an estimated 19.3 million people suffering from cancer in 2020, and the cancer lord is not far away from everyone [1].
In recent years, with the improvement of medical care, the incidence of infection-related cancers has decreased significantly, but lifestyle changes have led to an increasing incidence of non-infection-related cancers [2], and chronic mild inflammation may be the intermediate link between lifestyle and cancer, but there is some controversy. Therefore, identifying the effects of chronic inflammation on cancer and exploring related inflammatory markers are crucial to cancer prevention [3].
C-reactive protein (CRP) is an acute phase reactive protein synthesized in the liver and is widely used as a marker of chronic mild inflammation. In the absence of infection or injury, CRP levels are stable in the body, so their elevation may reflect chronic, mild inflammation levels [4]. Studies have shown a correlation between CRP and the risk of developing ovarian, colorectal, breast and lung cancers, while the association with other specific sites of cancer, particularly the risk of rare cancers, remains to be clarified.
Recently, Professor Ryoko Kato of the National Cancer Center of Japan and his team published the latest research results in the British Journal of Cancer, which found that the overall cancer risk of the general population showed an upward trend with the increase in CRP levels, and the highest CRP value was related to the increase in the overall cancer risk of 28%; corresponding to the specific location, the higher CRP level was related to the increased risk of colorectal cancer, lung cancer, breast cancer, biliary cancer, kidney cancer and leukemia. Therefore, CRP is expected to become a marker for screening some cancers [5].
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So, how did this experiment work?
This study is based on a prospective study of large population cohorts conducted by the Japan Public Health Center. Among them, 33736 participants from 9 public health centers in Japan formed a full cohort of the study, and 4456 randomly selected from the whole cohort to form a sub-cohort.
At the time of the 19-year follow-up, a total of 3608 participants in the whole cohort were diagnosed with cancer, and the sub-cohort was screened by strict entry criteria, and finally 4286 participants were included in the analysis, of which 496 were finally diagnosed with cancer.
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Next, let's take a look at the main data from this study.
At a median follow-up of 15.6 years, cancer patients in the case cohort tended to be male, elderly, smokers, and drinkers with a history of chronic disease and diabetes compared with subcohorts, and the median CRP of these patients was higher than that of the subcohort.
Basic characteristics of the cancer patient versus subcohort population in the case cohort
In subcohorts, quartiles were grouped by CRP levels, and people with higher CRP levels were older, smoked, active, and developed diabetes compared to those with the lowest quartile of CRP.
The results of the multivariate correction model analysis of CRP and overall cancer risk showed that participants were in the highest quartile array of CRP values, which was associated with a 28% increase in overall cancer risk compared to the lowest quartile array (HR=1.28, 95% CI: 1.11 1.48); the overall cancer risk increased with increased CRP levels, and this trend between the quartile arrays of CRP values was statistically significant (Ptrend
The results of the analysis of cancer at specific sites in a multivariate model showed that the participants' CRP levels were in the highest quartile group, which was associated with an increased risk of colorectal, lung, breast, biliary, kidney, and leukemia, and the trend between quartiles was statistically significant; in addition, CRP was in the third quartile group and was also associated with an increased risk of cholangiocarcinoma and kidney cancer.
CrP levels in relation to total cancer and cancer risk at specific sites
Analysis by sex showed a positive correlation between elevated CRP levels in both men and women and overall cancer risk, with similar results observed in colorectal and kidney cancers, and a positive correlation between CRP levels and biliary cancer risk in women but not in men. In terms of lung cancer, CRP levels were positively correlated with it in men and not in women. However, there was no evidence that sex had an effect on the association between CRP levels and overall and specific site cancer risk.
Effect of sex on the risk of cancer incidence in total and specific sites
To assess the interaction of sex, BMI levels, drinking and smoking status associated with CRP and cancer, the researchers stratified these factors and included an interaction analysis of these factors in the model.
A clear positive association between obesity, alcohol consumption, and smoking and overall cancer risk was found in subgroup analyses of overall cancer risk based on lifestyle factors; an interaction between obesity and CRP levels was observed, however, the association between CRP levels and overall cancer risk appeared to weaken in people who did not drink alcohol or occasionally drank alcohol and never smoked. In addition, lung cancer-only analyses showed no interaction between never-smokers and CRP levels on lung cancer risk.
Analysis in conjunction with lifestyle effects
Finally, the exclusion of early-diagnosed cancer cases did not diminish the degree of association between CRP levels and overall cancer risk; in addition, the correlation remained unchanged after excluding cases confirmed in the previous 9 years of follow-up; and a statistical correlation with CRP levels was observed for colorectal, lung, breast, biliary, and renal cancers.
Overall, the study in Asian populations suggests for the first time that higher CRP levels are associated with an increased risk of overall cancer, colorectal cancer, lung cancer, breast cancer, biliary tract cancer, kidney cancer, and leukemia, and also provide new evidence for the association of chronic mild inflammation with cancer.
The researchers believe that among the many inflammatory markers, the CRP detection method has high sensitivity and stable expression, and the introduction of CRP detection in health examinations may be another important option for cancer screening. However, before CRP can be widely used as a cancer marker, the relationship between it and cancer risk needs to be further confirmed.
bibliography:
1.Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-249. doi:10.3322/caac.21660
2.Bray F, Jemal A, Grey N, Ferlay J, Forman D. Global cancer transitions according to the Human Development Index (2008-2030): a population-based study. Lancet Oncol. 2012;13(8):790-801. doi:10.1016/S1470-2045(12)70211-5
3.Imhof A, Froehlich M, Brenner H, Boeing H, Pepys MB, Koenig W. Effect of alcohol consumption on systemic markers of inflammation. Lancet. 2001;357(9258):763-767. doi:10.1016/S0140-6736(00)04170-2
4.Pepys MB, Hirschfield GM. C-reactive protein: a critical update [published correction appears in J Clin Invest. 2003 Jul;112(2):299]. J Clin Invest. 2003;111(12):1805-1812. doi:10.1172/JCI18921
Responsible Editor 丨 Tan Shuo