Περίληψη:
Background
Obesity is positively associated with colorectal cancer. Recently, body
size subtypes categorised by the prevalence of hyperinsulinaemia have
been defined, and metabolically healthy overweight/obese individuals
(without hyperinsulinaemia) have been suggested to be at lower risk of
cardiovascular disease than their metabolically unhealthy
(hyperinsulinaemic) overweight/obese counterparts. Whether similarly
variable relationships exist for metabolically defined body size
phenotypes and colorectal cancer risk is unknown.
Methods and Findings
The association of metabolically defined body size phenotypes with
colorectal cancer was investigated in a case-control study nested within
the European Prospective Investigation into Cancer and Nutrition (EPIC)
study. Metabolic health/body size phenotypes were defined according to
hyperinsulinaemia status using serum concentrations of C-peptide, a
marker of insulin secretion. A total of 737 incident colorectal cancer
cases and 737 matched controls were divided into tertiles based on the
distribution of C-peptide concentration amongst the control population,
and participants were classified as metabolically healthy if below the
first tertile of C-peptide and metabolically unhealthy if above the
first tertile. These metabolic health definitions were then combined
with body mass index (BMI) measurements to create four metabolic
health/body size phenotype categories: (1) metabolically healthy/normal
weight (BMI < 25 kg/m(2)), (2) metabolically healthy/overweight (BMI >=
25 kg/m2), (3) metabolically unhealthy/normal weight (BMI < 25 kg/m2),
and (4) metabolically unhealthy/overweight (BMI >= 25 kg/m2).
Additionally, in separate models, waist circumference measurements
(using the International Diabetes Federation cut-points [>= 80 cm for
women and >= 94 cm for men]) were used (instead of BMI) to create the
four metabolic health/body size phenotype categories. Statistical tests
used in the analysis were all two-sided, and a p-value of <0.05 was
considered statistically significant. In multivariable-adjusted
conditional logistic regression models with BMI used to define
adiposity, compared with metabolically healthy/normal weight
individuals, we observed a higher colorectal cancer risk among
metabolically unhealthy/normal weight (odds ratio [OR] = 1.59, 95% CI
1.10-2.28) and metabolically unhealthy/overweight (OR = 1.40, 95% CI
1.01-1.94) participants, but not among metabolically healthy/overweight
individuals (OR = 0.96, 95% CI 0.65-1.42). Among the overweight
individuals, lower colorectal cancer risk was observed for metabolically
healthy/overweight individuals compared with metabolically
unhealthy/overweight individuals (OR = 0.69, 95% CI 0.49-0.96). These
associations were generally consistent when waist circumference was used
as the measure of adiposity. To our knowledge, there is no universally
accepted clinical definition for using C-peptide level as an indication
of hyperinsulinaemia. Therefore, a possible limitation of our analysis
was that the classification of individuals as being
hyperinsulinaemic-based on their C-peptide level-was arbitrary. However,
when we used quartiles or the median of C-peptide, instead of tertiles,
as the cut-point of hyperinsulinaemia, a similar pattern of associations
was observed.
Conclusions
These results support the idea that individuals with the metabolically
healthy/overweight phenotype (with normal insulin levels) are at lower
colorectal cancer risk than those with hyperinsulinaemia. The
combination of anthropometric measures with metabolic parameters, such
as C-peptide, may be useful for defining strata of the population at
greater risk of colorectal cancer.
Συγγραφείς:
Murphy, Neil
Cross, Amanda J.
Abubakar, Mustapha
Jenab,
Mazda
Aleksandrova, Krasimira
Boutron-Ruault, Marie-Christine
and Dossus, Laure
Racine, Antoine
Kuehn, Tilman
Katzke,
Verena A.
Tjonneland, Anne
Petersen, Kristina E. N.
Overvad,
Kim
Ramon Quiros, J.
Jakszyn, Paula
Molina-Montes, Esther
and Dorronsoro, Miren
Huerta, Jose-Maria
Barricarte, Aurelio and
Khaw, Kay-Tee
Wareham, Nick
Travis, Ruth C.
Trichopoulou,
Antonia
Lagiou, Pagona
Trichopoulos, Dimitrios
Masala,
Giovanna
Krogh, Vittorio
Tumino, Rosario
Vineis, Paolo and
Panico, Salvatore
Bueno-de-Mesquita, H. Bas
Siersema, Peter D.
and Peeters, Petra H.
Ohlsson, Bodil
Ericson, Ulrika and
Palmqvist, Richard
Nystrom, Hanna
Weiderpass, Elisabete and
Skeie, Guri
Freisling, Heinz
Kong, So Yeon
Tsilidis, Kostas
and Muller, David C.
Riboli, Elio
Gunter, Marc J.
