Among all participants, nearly one-third of them were diagnosed as MS (n = 140346, 29.6%). As expected, the participants with MS have higher waist circumference, BMI, blood pressure, the plasma concentration of fasting glucose, TG, and CRP, but lower concentration of HDL cholesterol. MS participants appeared to be older, to have a higher multiple deprivation index, and to have less physical activity. Table 1 showed the baseline characteristics.
Table 1
Baseline characteristics of participants according to MS in the UK biobank cohort.
Metabolic syndrome (N) | No (n = 334583) | Yes (n = 140346) |
Average follow-up years, Mean (SD) | 6.58 (1.23) | 6.49 (1.30) |
Age at participation, Mean (SD) | 55.5 (8.15) | 58.3 (7.64) |
BMI, Mean (SD), kg/m2 | 25.9 (3.86) | 31.0 (4.90) |
Waist circumference, Mean (SD), cm | 85.8 (11.3) | 101 (12.1) |
HDL cholesterol, Mean (SD), mmol/L | 1.55 (0.366) | 1.22 (0.303) |
Triglycerides, Mean (SD), mmol/L | 1.44 (0.777) | 2.42 (1.19) |
Fasting glucose, Mean (SD), mmol/L | 4.88 (0.671) | 5.63 (1.87) |
SBP, Mean (SD), mm Hg | 137 (19.7) | 146 (17.9) |
DBP, Mean (SD), mm Hg | 80.9 (10.6) | 85.4 (10.3) |
Primary site of caner, N | | |
Larynx | 61 | 42 |
Tonsil | 92 | 42 |
Oral cavity | 181 | 111 |
Nasal cavity and sinuses | 16 | 6 |
Oropharynx | 14 | 7 |
Hypopharynx | 20 | 4 |
Others | 111 | 99 |
Gender, N (%) | | |
Female | 188906 (56.5%) | 66956 (47.7%) |
Male | 145677 (43.5%) | 73390 (52.3%) |
Education level, N (%) | | |
College or University degree | 117845 (35.2%) | 35265 (25.1%) |
Other | 162865 (48.7%) | 70220 (50.0%) |
unkonwn/missing | 53873 (16.1%) | 34861 (24.8%) |
Ethnicity, N (%) | | |
Non-White | 315381 (94.3%) | 131082 (93.4%) |
white | 17645 (5.3%) | 8492 (6.1%) |
unkonwn/missing | 1557 (0.5%) | 772 (0.6%) |
Index of multiple deprivation quintile, N (%) | | |
1th | 61047 (18.2%) | 20643 (14.7%) |
2th | 59990 (17.9%) | 21823 (15.5%) |
3th | 58520 (17.5%) | 23158 (16.5%) |
4th | 56301 (16.8%) | 25571 (18.2%) |
5th | 52601 (15.7%) | 29330 (20.9%) |
missing | 46124 (13.8%) | 19821 (14.1%) |
Smoking status, N (%) | | |
Current | 34587 (10.3%) | 15915 (11.3%) |
Previous | 107678 (32.2%) | 54704 (39.0%) |
Never | 190793 (57.0%) | 68809 (49.0%) |
unkonwn/missing | 1525 (0.5%) | 918 (0.7%) |
Alcohol consumption, N (%) | | |
Daily or almost daily | 72332 (21.6%) | 23976 (17.1%) |
1–4 times a week | 169384 (50.6%) | 62723 (44.7%) |
One to three times a month | 35496 (10.6%) | 17363 (12.4%) |
Special occasions only or never | 56642 (16.9%) | 35901 (25.6%) |
unkonwn/missing | 729 (0.2%) | 383 (0.3%) |
Physical activity, N (%) | | |
Low | 44878 (13.4%) | 26981 (19.2%) |
Moderate | 109466 (32.7%) | 45595 (32.5%) |
High | 117170 (35.0%) | 37074 (26.4%) |
unkonwn/missing | 63069 (18.9%) | 30696 (21.9%) |
Portions of fruit and vegetable intake, Mean (SD) | 4.66 (3.11) | 4.52 (3.16) |
NSAIDS, N (%) | | |
No | 209520 (62.6%) | 67714 (48.2%) |
Yes | 117629 (35.2%) | 70322 (50.1%) |
Missing | 7434 (2.2%) | 2310 (1.6%) |
CRP_C, N (%) | | |
No | 145619 (43.5%) | 30015 (21.4%) |
Yes | 161311 (48.2%) | 106964 (76.2%) |
Missing | 27653 (8.3%) | 3367 (2.4%) |
During an average follow-up of 6.5 years, we recorded 806 HNC cases. Overall, individuals with MS had no significant effect on risk of HNC compared to those without MS (HR, 1.05; 95%CI, 0.90–1.22). More MS components leaded to higher risk of HNC (3 components: HR, 1.04; 95%CI, 0.88–1.24; 4 components: HR, 1.00; 95%CI, 0.80–1.26; 5 components: HR, 1.30; 95%CI, 0.92–1.84), but no statistical differences were detected. Analysis of MS components reveals that individuals with dyslipidemia for TG (HR, 1.31; 95%CI, 1.31–1.51), hypertension (HR, 1.23; 95%CI, 1.02–1.48) and hyperglycemia (HR, 1.35; 95%CI, 1.14–1.61) had higher hazard for HNC (model 1). After being adjusted by age and gender (model 2), ethnic, education, Index of multiple deprivations, alcohol drinking status, smoking status, fruit and vegetable intake, physical activity, NSAIDS use and CRP (model 3), the association remained noticeably for hyperglycemia (HR, 1.22; 95%CI, 1.02–1.45). See details in Table 2.
Table 2
Risk of head and neck cancer according to MS and its components
| No of cases/ Person-years | Model 1 | Model 2 | Model 3 |
HR (95%CI) | P | HR (95%CI) | P | HR (95%CI) | P |
Presence of MS | | | | | | | |
No | 495/ 2201184 | Reference | | Reference | | Reference | |
Yes | 311/ 910374 | 1.27[1.10, 1.47] | 0.001 | 1.18[1.02, 1.36] | 0.023 | 1.05[0.90, 1.22] | 0.560 |
No. of MS components | | | | | | | |
0–2 | 483/2167132 | Reference | | Reference | | Reference | |
3 | 191/582520 | 1.25[1.06, 1.48] | 0.009 | 1.14[0.96, 1.35] | 0.126 | 1.04[0.88, 1.24] | 0.645 |
4 | 95/283291 | 1.26[1.01, 1.57] | 0.043 | 1.16[0.93, 1.45] | 0.187 | 1.00[0.80, 1.26] | 0.978 |
5 | 37/78614 | 1.70[1.22, 2.38] | 0.002 | 1.58[1.13, 2.21] | 0.008 | 1.30[0.92, 1.84] | 0.132 |
Center obesity | | | | | | | |
No | 500/2065978 | Reference | | Reference | | Reference | |
Yes | 304/1036668 | 1.10[0.95, 1.26] | 0.211 | 1.19[1.04, 1.38] | 0.015 | 1.04[0.90, 1.21] | 0.592 |
Dyslipidaemia for TG | | | | | | | |
No | 141/845849 | Reference | | Reference | | Reference | |
Yes | 665/2262915 | 1.31[1.13, 1.51] | < 0.001 | 1.06[0.91, 1.23] | 0.461 | 0.95[0.81, 1.10] | 0.472 |
Dyslipidaemia for HDL | | | | | | | |
No | 301/1501095 | Reference | | Reference | | Reference | |
Yes | 464/1438442 | 1.16[0.98, 1.39] | 0.091 | 1.17[0.98, 1.39] | 0.087 | 1.01[0.84, 1.22] | 0.877 |
Hypertention | | | | | | | |
No | 528/2095502 | Reference | | Reference | | Reference | |
Yes | 160/568287 | 1.23[1.02, 1.48] | 0.027 | 1.02[0.84, 1.22] | 0.874 | 1.00[0.82, 1.20] | 0.973 |
Hyperglycaemia | | | | | | | |
No | 529/2226708 | Reference | | Reference | | Reference | |
Yes | 174/459089 | 1.35[1.14, 1.61] | 0.001 | 1.26[1.06, 1.5] | 0.009 | 1.22[1.02, 1.45] | 0.028 |
model 1: unadjusted |
model 2: Age and gender-stratified model |
model 3: additionally adjusted for education, ethnic, Index of multiple deprivation, alcohol consumption, smoking status, physical activity, fruit and vegetable intake, NASIDS use and CRP; |
When assessing the non-linear effect between individual MS components and HNC incidence risk, we observed a significant U-shape association for waist circumference (Fig. 1A, p-non-linear = 0.004) and HDL (Fig. 1E, p-non-linear = 0.005). Further, we analyzed their association for each gender, which showed that there was no non-linear relation between male waist circumference (Fig. 1B, p-non-linear = 0.394), female HDL (Fig. 1G, p-non-linear = 0.879) and HNC risk. However, a U-shape association between female waist circumference (Fig. 1C, p-non-linear = 0.031), male HDL (Fig. 1F, p-non-linear = 0.005) and HNC risk was observed. No relation was found for TG (Fig. 1D, p-non-linear = 0.098), SBP (Fig. 1H, p-non-linear = 0.849), DBP (Fig. 1I, p-non-linear = 0.258) and blood glucose (Fig. 1J, p-non-linear = 0.075). Based on this results, we divided the female waist circumference and male HDL into two sections with 93.16 cm and 1.45 mmol/L respectively according to the lowest point of U-shape curves to further perform linear analysis.
The linear effect between HNC risk and each MS component was showed in Table 3. Higher male waist circumference was correlated with elevated HNC risk (HR, 1.10; 95%CI, 1.02–1.20). Low female waist circumference (< 93.16 cm) showed no influence on the risk of HNC (HR, 0.92; 95%CI, 0.78–1.08); however, high female waist circumference (≥ 93.16 cm) was positively correlated with HNC risk (HR, 1.47; 95%CI, 1.15–1.89). Interestingly, higher male HDL increased HNC risk (HR, 1.19; 95%CI, 1.04, 1.36) when the concentration was more than 1.45 mmol/L. Male participants had no significant increased risk of HNC (HR, 0.94; 95%CI, 0.85–1.04) when HDL was less than 1.45 mmol/L and there was no correlation between female HDL with HNC risk (HR, 1.08; 95%CI, 0.92–1.27). Higher blood glucose was correlated with higher HNC risk (HR, 1.06; 95%CI, 1.00-1.12). No relation was found for TG (HR, 0.99; 95%CI, 0.93–1.07), SBP (HR, 1.03; 95%CI, 0.96–1.10) and DBP (HR, 1.00; 95%CI, 0.93–1.08).
Table 3
Risk of head and neck cancer in the UK biobank cohort in relation to MS components
MS components | Model 1 | Model 2 | Model 3 |
HR (95% CI) | P | HR (95% CI) | P | HR (95% CI) | P |
Waist circumference (male) | 1.19[1.10, 1.28] | < 0.001 | 1.19[1.10, 1.28] | < 0.001 | 1.10[1.02,1.20] | 0.019 |
Waist circumference (female) | | | | | | |
<93.16 cm | 0.94[0.80, 1.11] | 0.469 | 0.94[0.80, 1.11] | 0.471 | 0.92[0.78, 1.08] | 0.311 |
≥93.16 cm | 1.42[1.11, 1.80] | 0.005 | 1.41[1.11, 1.80] | 0.005 | 1.47[1.15, 1.89] | 0.003 |
Triglycerides (mmol/L) | 1.12[1.05, 1.20] | < 0.001 | 1.03[0.97, 1.11] | 0.339 | 0.97[0.91, 1.04] | 0.407 |
HDL cholesterol (male) | | | | | | |
<1.45 mmol/L | 0.88[0.80. 0.98] | 0.014 | 0.88[0.80. 0.98] | 0.014 | 0.94[0.85, 1.04] | 0.208 |
≥1.45 mmol/L | 1.23[1.08, 1.40] | 0.002 | 1.23[1.08, 1.41] | 0.001 | 1.19[1.04, 1.36] | 0.009 |
HDL cholesterol (female) | 1.02[0.87, 1.18] | 0.830 | 1.02[0.88, 1.18] | 0.821 | 1.08[0.92, 1.27] | 0.344 |
Diastolic blood pressure (mmHg) | 1.07[1.00, 1.05] | 0.043 | 0.99[0.92, 1.06] | 0.716 | 0.99[0.93, 1.07] | 0.848 |
Systolic blood pressure (mmHg) | 1.09[1.01, 1.17] | 0.018 | 1.03[0.96, 1.11] | 0.415 | 1.03[0.96, 1.10] | 0.451 |
Blood glucose (mmol/L) | 1.09[1.03, 1.15] | 0.002 | 1.07[1.01, 1.13] | 0.018 | 1.06[1.00, 1.12] | 0.044 |
model 1: unadjusted |
model 2: Age and gender-stratified model |
model 3: additionally adjusted for education, ethnic, Index of multiple deprivation, alcohol consumption, smoking status, physical activity, fruit and vegetable intake, NASIDS use and CRP; |
We further explore the relation between HNC incidence risk and CRP, the combined effect of CRP and MS as well. Elevated CRP more than 1.00 mg/dL elevated the risk for HNC (HR, 1.21; 95%CI, 1.02–1.43) compared to it lower than 1.00 mg/dL (model 3). After evaluating the combined effect of CRP and MS, it was found that both no MS plus elevated CRP (HR, 1.22; 95%CI, 1.02–1.47) and MS plus elevated CRP (HR, 1.29; 95%CI, 1.05–1.58) participants had increased HNC risk compared to those without MS and CRP < 1.00 mg/dL. See details in Table 4.
Table 4
Hazard ratios (HR) with 95% confidence intervals (CI) for head and neck cancer by CRP and joint effect of MS and CRP
| No. of cases / Person-years | Model 1 | Model 2 | Model 3 |
HR (95% CI) | P | HR (95% CI) | P | HR (95% CI) | P |
CRP | | | | | | | |
༜ 1.00 mg/dL | 223/1155432 | Reference | | Reference | | Reference | |
≥ 1.00 mg/dL | 531/1750092 | 1.39[1.18, 1.62] | < 0.001 | 1.44[1.23, 1.68] | < 0.001 | 1.21[1.03, 1.42] | 0.021 |
Joint effect of MS and CRP | | | | | | | |
No MS/CRP ༜ 1.00 mg/dL | 181/1027524 | Reference | | Reference | | Reference | |
No MS/CRP ≥ 1.00 mg/dL | 327/1153876 | 1.42[1.19, 1.72] | < 0.001 | 1.45[1.21, 1.73] | < 0.001 | 1.22[1.02, 1.47] | 0.033 |
MS/CRP ༜ 1.00 mg/dL | 42/127908 | 1.50[1.07, 2.10] | 0.018 | 1.30[0.93, 1.82] | 0.126 | 1.20[0.85, 1.68] | 0.298 |
MS/CRP ≥ 1.00 mg/dL | 204/596216 | 1.58[1.29, 1.93] | < 0.001 | 1.61[1.31, 1.96] | < 0.001 | 1.29[1.05, 1.58] | 0.017 |
model 1: Unadjusted |
model 2: Age and gender-stratified model |
model 3: additionally adjusted for education, ethnic, Index of multiple deprivation, alcohol consumption, smoking status, physical activity, fruit and vegetable intake, and NASIDS use; |