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Background: The close association of abdominal obesity rather than general obesity with colorectal cancer (CRC) risk might be mediated by IR and inflammation, which has never been systematically explored in large-scale prospective studies., Methods: We prospectively examined the mediation effects of the fasting triglyceride-glucose (TyG) index and C-reactive protein (CRP) on the associations of obesity (general and abdominal) with CRC risk among 93,659 participants. We used the Cox proportional hazards regression models and subgroup analyses to evaluate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) of CRC. The CAUSALMED procedure was used to perform the mediation analyses., Results: During 13.02 years of follow-up, a total of 586 CRC cases were verified. Male participants with general obesity and abdominal obesity had a 1.29-fold and a 1.28-fold increased risk of CRC. However, a significant association was only observed among female individuals with abdominal obesity. Both TyG index and CRP were associated with an elevated risk of CRC, and A significant interaction between the TyG index and CRP was found for the risk of CRC (P for interaction<0.05). CRP and the TyG index significantly mediated the positive association between abdominal obesity and CRC risk., Conclusion: CRP and TyG index increased the risk of CRC independently and synergistically. Mediation effects of CRP and the TyG index were found for the association between abdominal obesity and CRC risk., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Liu, Qian, Wang, Ma, Cao, Zhang and Qu.)

Serum uric acid (SUA) may play an important role in the occurrence of colorectal cancer (CRC). This study aims to explore the association of SUA with the risk of CRC incidence by drawing data from the Kailuan Study. We prospectively examined the association between SUA and risk of CRC incidence among 93,356 Chinese. Eligible participants were divided into three groups based on their tertiles of SUA. Cox proportional hazards regression was used to calculate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) of CRC. During a median follow-up of 13.02 years, 583 new-onset CRC cases were identified. After adjustments were made for confounders, participants in the highest tertiles of SUA exhibited a 1.55-fold increased risk of CRC compared with patients with the lowest SUA levels (HR T3 vs. T1  = 1.55, 95% CI: 1.09-2.30). The associations of SUA with the risk of CRC were slightly reduced but remained substantial in the competing risk analyses when treating CRC unrelated death as the competing risk event. This study found a positive association of SUA with CRC incidence. Specific prevention efforts could be focused on the population with higher levels of SUA., (© 2022. The Author(s).)

Background: No previous prospective research has explored the association of the TyG (fasting triglyceride-glucose) index and TG/HDL-C ratio as insulin resistance markers with the risk of colorectal cancer (CRC) incidence in the Northern Chinese population., Methods: In this prospective cohort study, we included 93,659 cancer-free participants with the measurements of TyG index and TG/HDL-C ratio. Participants were divided by the quartiles of the TyG index or TG/HDL-C ratio. The associations of TyG index, TG/HDL-C ratio, and their components with CRC risk were assessed using Cox proportional hazards regression models., Results: During a median follow-up of 13.02 years, 593 incident CRC cases were identified. Compared with the lowest quartile of the TyG index (Q1), the risk of CRC was higher in persons in the third (Q3) and highest quartiles (Q4) of the TyG index, with corresponding multivariable-adjusted HRs (95% CI) of 1.36 (1.06, 1.76) and 1.50 (1.19, 1.91), respectively. The elevated risks of CRC incidence were observed in people in the second, third, and highest quartiles of the TG/HDL-C ratio groups, with corresponding multivariable-adjusted HRs (95% CI) of 1.33 (1.05, 1.70), 1.36 (1.07, 1.73) and 1.37 (1.07, 1.75), respectively., Conclusions: Elevated TyG index and TG/HDL-C ratio were associated with a higher risk of developing CRC among adults in Northern China., (© 2022. The Author(s).)

Background: Inflammation and metabolic syndrome (MetS) may act synergistically and possibly accelerate the initiation and progression of colorectal cancer (CRC). We prospectively examined the joint effect of MetS and inflammation on the risk of CRC., Methods: We studied 92,770 individuals from the Kailuan study. MetS was defined based on the presence of three or more of the following components. (1) high glucose: FPG > 5.6 mmol/L; (2) high blood pressure: SBP ≥ 130 mmHg or DBP ≥ 85 mmHg; (3) high triglycerides: triglycerides > 1.69 mmol/L; (4) low HDL-C: HDL-C < 1.04 mmol/L in men or 1.29 mmol/L in women; and (5) visceral adiposity: waist circumference ≥ 85 cm in men or 80 cm in women. Inflammation was defined as hs-CRP ≥ 3 mg/L. We divided participants into four groups for the primary exposure according to the presence/absence of inflammation and presence/absence of MetS. Cox proportional hazards regression models were used to evaluate the association of MetS and/or inflammation with the risk of CRC., Results: Compared with metabolically healthy noninflammatory individuals, inflammatory participants without MetS and inflammatory participants with MetS were associated with a 1.3-fold and 4.18-fold increased risk of CRC with corresponding HRs (95% CI) of 1.34 (1.09, 1.64) and 4.18 (3.11, 5.62), respectively. The combination of MetS and inflammation was associated with the highest risk of CRC in all subgroups, especially among participants who were female, in younger age, and obese. Sensitivity analyses further validated our primary findings., Conclusions: We found the combination of MetS and inflammation could significantly increase the risk of CRC. Including CRP in the diagnosis of MetS may help to identify additional high-risk participants who should be targeted for early diagnosis and prevention of CRC. Trial registration Kailuan study, ChiCTR-TNRC-11001489. Registered 24 August, 2011-Retrospectively registered, http:// www.chictr.org.cn/showprojen.aspx?proj=8050., (© 2022. The Author(s).)

A single CRP measurement is insufficient to examine the association of long-term patterns of CRP concentration with cancer risk. We prospectively examined the relationship between CRP trajectory patterns and new-onset cancers among 52 276 participants. Latent mixture modeling was used to identify CRP trajectories. Cox proportional hazards regression models were used to evaluate the association between CRP trajectory patterns and the risk of overall and specific-site cancer. Four CRP trajectories patterns were identified: low-stable pattern (n = 43 258), moderate-increasing pattern (n = 2591), increasing-decreasing pattern (n = 2068) and elevated-decreasing pattern (n = 4359). Relative to the low-stable pattern, the moderate-increasing trajectory pattern was associated with an elevated risk of overall, lung, breast, leukemia, bladder, stomach, colorectal, liver, gallbladder or extrahepatic bile duct cancer and leukemia. Participants in the increasing-decreasing trajectory pattern were associated with an elevated risk of overall, lung, breast, bladder, pancreatic and liver cancer. The increasing-decreasing trajectory pattern was also associated with decreased risk of colorectal cancer in the multivariate analyses. Elevated-decreasing trajectory pattern was associated with increased risk of leukemia and decreased risk of esophageal and colorectal cancer. CRP trajectories play an important role in the occurrence of cancers, especially in the lung, breast, bladder, stomach, colorectal, liver, gallbladder and extrahepatic bile duct cancer and leukemia., (© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)