Metabolic risk score and cancer risk: pooled analysis of seven cohorts

Abstract

Background: There are few data on the joint influence of metabolic factors on risk of separate cancers.

Methods: We analysed data on body mass index, blood pressure and plasma levels of glucose, total cholesterol and triglycerides from seven European cohorts comprising 564 596 men and women with a mean age of 44 years. We weighted those factors equally into a standardized metabolic risk score [MRS, mean = 0, standard deviation (SD) = 1], with an individual's level indicated as SDs from the sex- and cohort-specific means. Cancer hazard ratios were calculated by Cox regression with age as timescale and with relevant adjustments including smoking status. All statistical tests were two-sided.

Results: During a mean follow-up of 12 years, 21 593 men and 14 348 women were diagnosed with cancer. MRS was linearly and positively associated with incident cancer in total and at sites (P < 0.05). In men, risk per SD MRS was increased by 43% (95% confidence interval: 27-61) for renal cell cancer, 43% (16-76) for liver cancer, 29% (20-38) for colon cancer, 27% (5-54) for oesophageal cancer, 20% (9-31) for rectal cancer, 19% (4-37) for leukaemias, 15% (1-30) for oral cancer and 10% (2-19) for bladder cancer. In women, risk increases per SD MRS were 56% (42-70) for endometrial cancer, 53% (29-81) for pancreatic cancer, 40% (16-67) for renal cell cancer, 27% (9-47) for cervical cancer and 17% (3-32) for rectal cancer.

Conclusion: This largest study to date on the joint influence of metabolic factors on risk of separate cancers showed increased risks for several cancers, in particular renal cell and liver cancer in men and endometrial and pancreatic cancer in women.

Keywords: cohort studies; metabolic syndrome x; neoplasms.

Figure 1.

Hazard ratio (HR, black line) and 95% confidence interval (shaded area) of cancer incidence (A) (n cases = 21 593) and cancer mortality (B) (n cases = 8572) in men, and cancer incidence (C) (n cases = 14 348) and cancer mortality (D) (n cases = 4405) in women, by the metabolic risk score (mean = 0, SD = 1). Models were derived from restricted cubic spline regression, with knots placed at percentiles 5, 35, 65 and 95. Attained age was used as timescale, and models were stratified by cohort and birth year and adjusted for baseline age and smoking status. HRs were corrected for a regression dilution ratio of 0.69 for metabolic risk score by exp(log(HR)/0.69). Participants with values more extreme than ± 3 SD were excluded from the analyses (n excluded ≤ 1845). P-value LR test, linear-spline, refers to likelihood-ratio tests of the linear model nested in a model with addition of splines.

Figure 2.

Hazard ratio (HR) and 95% confidence interval of incident cancer at separate sites in men (A), women (B) and men and women combined (C) by the metabolic risk score (MRS, mean = 0, SD = 1). HRs were derived from Cox regression models with attained age as timescale, strata for cohort, birth year and sex and adjustment for baseline age and smoking status. HRs were corrected for a regression dilution ratio of 0.69 for metabolic risk score by exp(log(HR)/0.69). ICD-7 180.0 and 180.9 denoting renal cell cancer, and ICD-7172 denoting endometrial cancer, include a fraction of tumours that morphologically differ from the clinical classification of these cancers. HRs for cancer of the stomach, colon and pancreas differed significantly between men and women, so these cancers are not included in (C). P_het refers to P-value for heterogeneity between cohorts which was tested by likelihood ratio tests in which a model with the continuous metabolic risk score was compared with a model additionally including a product term of metabolic risk score and cohort.