Effet du surpoids sur le risque de cancer?

[Nutrimuscle-Conseils]

Adiposity, metabolites, and colorectal cancer risk: Mendelian randomization study
Caroline J. Bull, BMC Medicine volume 18, Article number: 396 (2020)

Background
Higher adiposity increases the risk of colorectal cancer (CRC), but whether this relationship varies by anatomical sub-site or by sex is unclear. Further, the metabolic alterations mediating the effects of adiposity on CRC are not fully understood.

Methods
We examined sex- and site-specific associations of adiposity with CRC risk and whether adiposity-associated metabolites explain the associations of adiposity with CRC. Genetic variants from genome-wide association studies of body mass index (BMI) and waist-to-hip ratio (WHR, unadjusted for BMI; N = 806,810), and 123 metabolites from targeted nuclear magnetic resonance metabolomics (N = 24,925), were used as instruments. Sex-combined and sex-specific Mendelian randomization (MR) was conducted for BMI and WHR with CRC risk (58,221 cases and 67,694 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry). Sex-combined MR was conducted for BMI and WHR with metabolites, for metabolites with CRC, and for BMI and WHR with CRC adjusted for metabolite classes in multivariable models.

Results
In sex-specific MR analyses, higher BMI (per 4.2 kg/m2) was associated with 1.23 (95% confidence interval (CI) = 1.08, 1.38) times higher CRC odds among men (inverse-variance-weighted (IVW) model); among women, higher BMI (per 5.2 kg/m2) was associated with 1.09 (95% CI = 0.97, 1.22) times higher CRC odds. WHR (per 0.07 higher) was more strongly associated with CRC risk among women (IVW OR = 1.25, 95% CI = 1.08, 1.43) than men (IVW OR = 1.05, 95% CI = 0.81, 1.36). BMI or WHR was associated with 104/123 metabolites at false discovery rate-corrected P ≤ 0.05; several metabolites were associated with CRC, but not in directions that were consistent with the mediation of positive adiposity-CRC relations. In multivariable MR analyses, associations of BMI and WHR with CRC were not attenuated following adjustment for representative metabolite classes, e.g., the univariable IVW OR for BMI with CRC was 1.12 (95% CI = 1.00, 1.26), and this became 1.11 (95% CI = 0.99, 1.26) when adjusting for cholesterol in low-density lipoprotein particles.

Conclusions
Our results suggest that higher BMI more greatly raises CRC risk among men, whereas higher WHR more greatly raises CRC risk among women. Adiposity was associated with numerous metabolic alterations, but none of these explained associations between adiposity and CRC. More detailed metabolomic measures are likely needed to clarify the mechanistic pathways.

[Nutrimuscle-Conseils]

Combined association of general and central obesity with incidence and mortality of cancers in 22 sites
Solange Parra-Soto, The American Journal of Clinical Nutrition, 31 December 2020

Background
Body mass index (BMI) and waist circumference (WC) are measures of general and central obesity, respectively, and both have been shown to be associated with cancer. However, there is insufficient evidence of their combined association with the risk of cancer.

Objectives
This study aimed to investigate the associations of combinations of BMI and WC with cancer at 22 sites.

Methods
A total of 386,101 (54.5% women) UK Biobank participants aged from 37 to 73 y were included. The outcomes were incidence of and mortality from cancer at 22 sites. Participants were categorized as normal weight (BMI 18.5–24.9) or overweight (including obese, BMI ≥ 25) and as normal WC or centrally obese (WC ≥ 94 cm for men and ≥80 cm for women). Four mutually exclusive groups were derived: 1) normal weight without central obesity, 2) normal weight with central obesity, 3) overweight without central obesity, and 4) overweight with central obesity. We used Cox proportional hazards models to estimate HRs and 95% CIs.

Results
The mean follow-up period was 8.8 y. Compared with participants with normal weight and WC, men who were overweight and centrally obese had higher cancer incidence risk at 3 sites [stomach (HR: 1.75; 95% CI: 1.33, 2.32; Padj = 0.002), kidney (HR: 1.45; 95% CI: 1.17, 1.81; Padj = 0.016), and colorectal (HR: 1.31; 95% CI: 1.17, 1.47; Padj < 0.001) cancer]. Similar associations were found at 4 sites in women [endometrial (HR: 2.48; 95% CI: 2.06, 2.98; Padj < 0.001), uterine (HR: 2.23; 95% CI: 1.89, 2.64; Padj < 0.001), kidney (HR: 1.84; 95% CI: 1.37, 2.46; Padj = 0.001), and breast (HR: 1.24; 95% CI: 1.16, 1.32; Padj < 0.001) cancer] and for all-cause cancer (HR: 1.07; 95% CI: 1.03, 1.10; Padj = 0.003). Only endometrial cancer mortality (HR: 3.28; 95% CI: 1.77, 6.07; Padj = 0.004) was significantly associated with being overweight and centrally obese.

Conclusions
The combination of general and central obesity was associated with a higher risk at several cancer sites and some associations were sex-specific.

[Nutrimuscle-Diététique]

Traduction de l'étude

Association combinée de l'obésité générale et centrale avec l'incidence et la mortalité des cancers dans 22 sites
Solange Parra-Soto, The American Journal of Clinical Nutrition, 31 décembre 2020

Contexte
L'indice de masse corporelle (IMC) et le tour de taille (WC) sont des mesures de l'obésité générale et centrale, respectivement, et il a été démontré que les deux sont associés au cancer. Cependant, il n'y a pas suffisamment de preuves de leur association combinée avec le risque de cancer.

Objectifs
Cette étude visait à étudier les associations de combinaisons d'IMC et de WC avec le cancer sur 22 sites.

Méthodes
Un total de 386 101 participants (54,5% de femmes) à la biobanque britannique âgés de 37 à 73 ans ont été inclus. Les résultats étaient l'incidence et la mortalité par cancer dans 22 sites. Les participants ont été classés en poids normal (IMC 18,5–24,9) ou en surpoids (y compris obèses, IMC ≥ 25) et en tant que WC normal ou obèse central (WC ≥ 94 cm pour les hommes et ≥ 80 cm pour les femmes). Quatre groupes mutuellement exclusifs ont été dérivés: 1) poids normal sans obésité centrale, 2) poids normal avec obésité centrale, 3) surpoids sans obésité centrale et 4) surpoids avec obésité centrale. Nous avons utilisé les modèles de risques proportionnels de Cox pour estimer les HR et les IC à 95%.

Résultats
La période moyenne de suivi était de 8,8 ans. Par rapport aux participants de poids normal et de WC normaux, les hommes en surpoids et obèses centralement présentaient un risque d'incidence de cancer plus élevé sur 3 sites [estomac (HR: 1,75; IC à 95%: 1,33, 2,32; Padj = 0,002), rein (HR: 1,45; IC à 95%: 1,17, 1,81; Padj = 0,016) et cancer colorectal (HR: 1,31; IC à 95%: 1,17, 1,47; Padj <0,001)]. Des associations similaires ont été trouvées sur 4 sites chez la femme [endomètre (HR: 2,48; IC à 95%: 2,06, 2,98; Padj <0,001), utérin (HR: 2,23; IC à 95%: 1,89, 2,64; Padj <0,001), rein ( HR: 1,84; IC à 95%: 1,37, 2,46; Padj = 0,001) et du sein (HR: 1,24; IC à 95%: 1,16, 1,32; Padj <0,001) cancer] et pour le cancer toutes causes (HR: 1,07; 95 % CI: 1,03, 1,10; Padj = 0,003). Seule la mortalité par cancer de l'endomètre (HR: 3,28; IC à 95%: 1,77, 6,07; Padj = 0,004) était significativement associée au surpoids et à l'obésité centrale.

Conclusions
La combinaison de l'obésité générale et centrale était associée à un risque plus élevé à plusieurs sites de cancer et certaines associations étaient spécifiques au sexe.