Measured Adiposity in Relation to Head and Neck Cancer Risk in the European Prospective Investigation into Cancer and Nutrition

Ward, Heather; Wark, Petra A.; Muller, David C.; Steffen, Annika; Johansson, Mattias; Norat, Teresa; Gunter, Marc J.; Overvad, Kim; Dahm, Christina C.; Halkjær, Jytte; Tjønneland, Anne; Boutron-Ruault, Marie Christine; Fagherazzi, Guy; Mesrine, Sylvie; Brennan, Paul; Freisling, Heinz; Li, Kuanrong; Kaaks, Rudolf; Trichopoulou, Antonia; Λάγιου, Παγώνα; Panico, S.; Grioni, Sara; Tumino, Rosario; Víneis, Paolo; Palli, Domenico; Peeters, Petra H.; Bueno-De-Mesquita, H. Bas; Weiderpass, Elisabete; Agudo, Antonio; Quiŕos, J. Ramón; Larrañaga, Nerea; Ardanáz, Eva; Huerta, José María; Sánchez, María José; Laurell, Göran; Johansson, Ingegerd; Westin, Ulla; Wallström, Peter; Bradbury, Kathryn E.; Wareham, Nicholas J.; Khaw, Kay Tee; Pearson, Clare; Boeing, Heiner; Riboli, Elio

doi:10.1158/1055-9965.epi-16-0886

Cited by 11 publications

(8 citation statements)

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“… 19 , 33 Some discrepancies for hip size may also be due to the mutual adjustment used in previous studies for HC and WC, which are correlated strongly with each other and, as explained above, are both proxy measures of total body size. Thus, we could not confirm a reported inverse association of HC adjusted for WC with head and neck cancer in men, 25 although our results were directionally consistent in women, but found an inverse association of HI with liver cancer, not reported for HC adjusted for WC. 29 Further, we could not confirm a reported inverse association of HC adjusted for body weight with RCC in men, 34 but found evidence for an inverse association of HI with clear‐cell adenocarcinoma, especially in women.…”

Section: Discussioncontrasting

confidence: 99%

“…The main compatibilities between our findings and previous reports concern cancers associated more strongly with waist size. Thus, positive associations based on WC or WHR, with or without adjustment for BMI and in some studies for HC, have previously been reported for cancers of the head and neck, 23 , 24 , 25 esophagus and gastric cardia (adenocarcinoma), 21 , 24 , 26 colon, 24 , 27 , 28 liver, 24 , 29 lung overall, 30 and bladder (men). 24 , 31 , 32 Nevertheless, while we observed comparable associations with ABSI and WHI, previous studies have often reported positive associations with WC but not with WHR adjusted for BMI.…”

Section: Discussionmentioning

confidence: 77%

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A Body Shape Index (ABSI), hip index, and risk of cancer in the UK Biobank cohort

et al. 2021

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Abdominal size is associated positively with the risk of some cancers but the influence of body mass index (BMI) and gluteofemoral size is unclear because waist and hip circumference are strongly correlated with BMI. We examined associations of 33 cancers with A Body Shape Index (ABSI) and hip index (HI), which are independent of BMI by design, and compared these with waist and hip circumference, using multivariable Cox proportional hazards models in UK Biobank. During a mean follow‐up of 7 years, 14,682 incident cancers were ascertained in 200,289 men and 12,965 cancers in 230,326 women. In men, ABSI was associated positively with cancers of the head and neck (hazard ratio HR = 1.14; 95% confidence interval 1.03–1.26 per one standard deviation increment), esophagus (adenocarcinoma, HR = 1.27; 1.12–1.44), gastric cardia (HR = 1.31; 1.07–1.61), colon (HR = 1.18; 1.10–1.26), rectum (HR = 1.13; 1.04–1.22), lung (adenocarcinoma, HR = 1.16; 1.03–1.30; squamous cell carcinoma [SCC], HR = 1.33; 1.17–1.52), and bladder (HR = 1.15; 1.04–1.27), while HI was associated inversely with cancers of the esophagus (adenocarcinoma, HR = 0.89; 0.79–1.00), gastric cardia (HR = 0.79; 0.65–0.96), colon (HR = 0.92; 0.86–0.98), liver (HR = 0.86; 0.75–0.98), and multiple myeloma (HR = 0.86; 0.75–1.00). In women, ABSI was associated positively with cancers of the head and neck (HR = 1.27; 1.10–1.48), esophagus (SCC, HR = 1.37; 1.07–1.76), colon (HR = 1.08; 1.01–1.16), lung (adenocarcinoma, HR = 1.17; 1.06–1.29; SCC, HR = 1.40; 1.20–1.63; small cell, HR = 1.39; 1.14–1.69), kidney (clear‐cell, HR = 1.25; 1.03–1.50), and post‐menopausal endometrium (HR = 1.11; 1.02–1.20), while HI was associated inversely with skin SCC (HR = 0.91; 0.83–0.99), post‐menopausal kidney cancer (HR = 0.77; 0.67–0.88), and post‐menopausal melanoma (HR = 0.90; 0.83–0.98). Unusually, ABSI was associated inversely with melanoma in men (HR = 0.89; 0.82–0.96) and pre‐menopausal women (HR = 0.77; 0.65–0.91). Waist and hip circumference reflected associations with BMI, when examined individually, and provided biased risk estimates, when combined with BMI. In conclusion, preferential positive associations of ABSI or inverse of HI with several major cancers indicate an important role of factors determining body shape in cancer development.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 77%

A Body Shape Index (ABSI), hip index, and risk of cancer in the UK Biobank cohort

et al. 2021

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“…Eight studies reported the association between BMI (n= 2,859 cases) and risk of HNC 11,12,[14][15][16][54][55][56] , with 15 studies reporting the association with type 2 diabetes (n= 17,582 cases) 12,[17][18][19][20]23,24,[57][58][59][60][61][62][63][64] , six studies hypertension (n= 12,151 cases) 12,[19][20][21][22][23] , and four studies dyslipidaemia (n= 6,410 cases) 12,19,20,65 and HNC risk (Table 2). Adjustments were made for potential confounders of two or more factors, including age, in all studies.…”

Section: Resultsmentioning

confidence: 99%

“…In the largest pooled analysis, obesity defined by higher BMI was associated with a protective effect for HNC in current smokers (hazard ratio (HR)= 0.76, 95%CI (0.71, 0.82), p <0.0001, per 5 kg/m 2 ) and conversely, a higher risk in never smokers (HR= 1.15, 95%CI (1.06, 1.24) per 5 kg/m 2 , p <0.001) 11 . More recent cohort studies have failed to show a clear association between BMI and HNC [12][13][14][15][16] . Similarly, a meta-analysis of observational studies investigating type 2 diabetes with oral and oropharyngeal subsites found an increased risk ratio (RR) of 1.15, 95%CI (1.02, 1.29) 17 .…”

Section: Introductionmentioning

confidence: 99%

Metabolic traits and the risk of head and neck cancer: a systematic review and meta-analysis

Gormley,

Richards,

Spiga

et al. 2023

Preprint

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Introduction The overall incidence of head and neck cancer (HNC) continues to rise, despite a decline in smoking rates, particularly within developed countries. Obesity and related metabolic traits have been attributed to a growth in cancer rate, so further exploration of these risk factors is warranted in HNC. A comprehensive systematic review and meta-analysis was conducted in order to obtain the most precise observational estimates between metabolic trait exposures and risk of HNC. Methods A search strategy was developed with an information and content specialists. Multiple databases including Cochrane Library, OVID SP versions of Medline, EMBASE, pre-prints and the grey literature were searched. The primary outcome for included studies was incident HNC and exposures included obesity defined by body mass index (BMI), type 2 diabetes, dyslipidaemia, and hypertension, using pre-specified definitions. A combined risk effect across studies was calculated using both fixed and random-effects meta-analysis. Heterogeneity was assessed between studies using the Cochrans Q and I2 statistical tests. The ROBINS-E preliminary tool was used to assess the bias in each included result. Results The search generated 7,316 abstracts, of these 197 full text articles were assessed for eligibility and 36 were included for full qualitative and quantitative synthesis. In the analysis of 5 studies investigating the association between obesity and incidence of HNC, there was an overall RR of 1.06 (95%CI (0.76, 1.49), P heterogeneity <0.024, I2= 73.2%) using a random-effects model. 6 studies reported on the association between type 2 diabetes and incidence of HNC, with an overall RR of 1.13 (95%CI (0.95, 1.34), P heterogeneity= <0.0001, I2= 80.0%) using a random-effects model. An increased risk of hypertension was consistent across HNC subsites, with the strongest association found in the larynx (RR= 1.17, 95%CI (1.10, 1.25), P heterogeneity= 0.186, I2= 37.7%). For dyslipidaemia, only 2 studies were available for meta-analysis in the laryngeal subsite, with some evidence of an increased risk association of both low high-density lipoprotein (RR= 1.12, 95%CI (1.07, 1.18), P heterogeneity= 0.103, I2= 62.5%) and high triglyceride levels (RR= 1.10, 95%CI (1.05, 1.15), P heterogeneity= 0.319, I2= 0.0%)) using random-effects models. Over 80% of studies were judged to be at Very High or High risk of bias using the ROBINS-E tool. Conclusion Despite individual studies suggesting an association between BMI and HNC, limited effect was demonstrated in this meta-analysis. There was evidence of an association between hypertension and dyslipidaemia on incident HNC, however caution is required due to the high levels of heterogeneity recorded in these studies. Observational associations are susceptible to confounding, bias and reverse causality so these results must be interpreted with caution. Future work should include meta-analysing studies separately by geographic region, as this appears to be a clear source of heterogeneity.

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“…In the same study, a greater waist circumference (WC) (HR⍰ ⍰1.04, 95%CI 1.03–1.05 per 5⍰cm, p ⍰< 0.001) and waist-to-hip ratio (WHR) (HR⍰1.07, 95%CI 1.05–1.09 per 0.1 unit, p < 0.001) were associated with increased HNC risk, which did not vary by smoking status (Gaudet et al, 2015). However, more recent cohort studies have failed to show a clear association between BMI and HNC (Cao et al, 2020; Diaz et al, 2021; Gribsholt et al, 2020; Jiang et al, 2021; Ward et al, 2017). A meta-analysis of observational studies investigating T2D with oral and oropharyngeal subsites, showed an increased risk ratio (RR) of 1.15, 95%CI 1.02–1.29, P heterogeneity = 0.277 (Gong, Wei, Yu, & Pan, 2015), a result which is consistent with more recent independent cohorts (Jiang et al, 2021; H.-B.…”

Section: Introductionmentioning

confidence: 99%

Evaluating the effect of metabolic traits on oral and oropharyngeal cancer risk using Mendelian randomization

Gormley

Dudding

Thomas

et al. 2022

Preprint

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IntroductionA recent World Health Organization report states that at least 40% of all cancer cases may be preventable, with smoking, alcohol consumption and obesity identified as three of the most important modifiable lifestyle factors. Established risk factors for head and neck cancer include tobacco use, alcohol consumption and human papillomavirus infection. Given the significant decline in smoking rates, particularly within developing countries, other potentially modifiable risk factors warrant investigation. Obesity and related metabolic disorders such as type 2 diabetes and hypertension have all been associated with head and neck cancer risk in multiple observational studies. However, obesity has also been correlated with other major head and neck cancer risk factors such as smoking, meaning independent effects are difficult to establish. Furthermore, selection bias, confounding or reverse causality may explain the findings from observational studies.MethodsTo overcome the challenges of observational studies, we conducted two-sample Mendelian randomization (inverse variance weighted (IVW) method) using genetic variants which were robustly associated with obesity, T2D and hypertension in genome-wide association studies (GWAS). Outcome data was taken from the largest available GWAS of 6,034 oral and oropharyngeal cases, with 6,585 controls.ResultsWe found limited evidence of a causal effect of genetically proxied body mass index (OR IVW 0.89, 95%CI 0.72–1.09, p = 0.26 per 1 SD in BMI (4.81 kg/m2)) on combined oral and oropharyngeal cancer risk. Similarly, there was limited evidence for genetically-proxied T2D (OR IVW 0.92, 95%CI 0.84–1.01, p = 0.09 per 1-log unit higher odds of T2D), or related traits including fasting glucose and insulin. Higher HbA1c resulted in a weak protective effect on combined oral and oropharyngeal cancer risk (OR IVW 0.56, 95%CI 0.32–1.00, p = 0.05 per 1-log-unit % higher HbA1c), which was not robust to sensitivity testing. Finally, there was limited evidence for an effect of systolic blood pressure on combined oral and oropharyngeal cancer risk (OR IVW 1.00, 95%CI 0.97–1.03, p = 0.89 per 1 unit mmHg increase). Smoking also appears to act as a mediator in the relationship between obesity and HNC in instrument-risk factor analyses.ConclusionThis analysis suggests the possibility that the effect of metabolic disorders may have been previously overestimated in observational studies. However, these cannot be directly compared given the differences in methodologies and the interpretation of estimates.

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Measured Adiposity in Relation to Head and Neck Cancer Risk in the European Prospective Investigation into Cancer and Nutrition

Cited by 11 publications

References 50 publications

A Body Shape Index (ABSI), hip index, and risk of cancer in the UK Biobank cohort

A Body Shape Index (ABSI), hip index, and risk of cancer in the UK Biobank cohort

Metabolic traits and the risk of head and neck cancer: a systematic review and meta-analysis

Evaluating the effect of metabolic traits on oral and oropharyngeal cancer risk using Mendelian randomization

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