Abstract
Obesity has been postulated to increase the risk of colorectal cancer by mechanisms involving insulin resistance and the metabolic syndrome. We examined the associations of body mass index (BMI), waist circumference, the metabolic syndrome, metabolic obesity phenotypes and homeostasis model-insulin resistance (HOMA-IR-a marker of insulin resistance) with risk of colorectal cancer in over 21,000 women in the Women's Health Initiative CVD Biomarkers subcohort. Women were cross-classified by BMI (18.5-<25.0, 25.0-<30.0 and ≥30.0 kg/m2) and presence of the metabolic syndrome into 6 phenotypes: metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy overweight (MHOW), metabolically unhealthy overweight (MUOW), metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO). Neither BMI nor presence of the metabolic syndrome was associated with risk of colorectal cancer, whereas waist circumference showed a robust positive association. Relative to the MHNW phenotype, the MUNW phenotype was associated with increased risk, whereas no other phenotype showed an association. Furthermore, HOMA-IR was not associated with increased risk. Overall, our results do not support a direct role of metabolic dysregulation in the development of colorectal cancer; however, they do suggest that higher waist circumference is a risk factor, possibly reflecting the effects of increased levels of cytokines and hormones in visceral abdominal fat on colorectal carcinogenesis.
| Original language | English (US) |
|---|---|
| Journal | International Journal of Cancer |
| DOIs | |
| State | Accepted/In press - Jan 1 2018 |
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Keywords
- Body mass index
- Colorectal cancer risk
- HOMA-IR
- Metabolic status
- Postmenopausal women
- Waist circumference
ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
Metabolic obesity phenotypes and risk of colorectal cancer in postmenopausal women. / Kabat, Geoffrey C.; Kim, Mimi; Stefanick, Marcia; Ho, Gloria Y.F.; Lane, Dorothy S.; Odegaard, Andrew O.; Simon, Michael S.; Bea, Jennifer W.; Luo, Juhua; Wassertheil-Smoller, Sylvia; Rohan, Thomas E.
In: International Journal of Cancer, 01.01.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Metabolic obesity phenotypes and risk of colorectal cancer in postmenopausal women
AU - Kabat, Geoffrey C.
AU - Kim, Mimi
AU - Stefanick, Marcia
AU - Ho, Gloria Y.F.
AU - Lane, Dorothy S.
AU - Odegaard, Andrew O.
AU - Simon, Michael S.
AU - Bea, Jennifer W.
AU - Luo, Juhua
AU - Wassertheil-Smoller, Sylvia
AU - Rohan, Thomas E.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Obesity has been postulated to increase the risk of colorectal cancer by mechanisms involving insulin resistance and the metabolic syndrome. We examined the associations of body mass index (BMI), waist circumference, the metabolic syndrome, metabolic obesity phenotypes and homeostasis model-insulin resistance (HOMA-IR-a marker of insulin resistance) with risk of colorectal cancer in over 21,000 women in the Women's Health Initiative CVD Biomarkers subcohort. Women were cross-classified by BMI (18.5-<25.0, 25.0-<30.0 and ≥30.0 kg/m2) and presence of the metabolic syndrome into 6 phenotypes: metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy overweight (MHOW), metabolically unhealthy overweight (MUOW), metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO). Neither BMI nor presence of the metabolic syndrome was associated with risk of colorectal cancer, whereas waist circumference showed a robust positive association. Relative to the MHNW phenotype, the MUNW phenotype was associated with increased risk, whereas no other phenotype showed an association. Furthermore, HOMA-IR was not associated with increased risk. Overall, our results do not support a direct role of metabolic dysregulation in the development of colorectal cancer; however, they do suggest that higher waist circumference is a risk factor, possibly reflecting the effects of increased levels of cytokines and hormones in visceral abdominal fat on colorectal carcinogenesis.
AB - Obesity has been postulated to increase the risk of colorectal cancer by mechanisms involving insulin resistance and the metabolic syndrome. We examined the associations of body mass index (BMI), waist circumference, the metabolic syndrome, metabolic obesity phenotypes and homeostasis model-insulin resistance (HOMA-IR-a marker of insulin resistance) with risk of colorectal cancer in over 21,000 women in the Women's Health Initiative CVD Biomarkers subcohort. Women were cross-classified by BMI (18.5-<25.0, 25.0-<30.0 and ≥30.0 kg/m2) and presence of the metabolic syndrome into 6 phenotypes: metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy overweight (MHOW), metabolically unhealthy overweight (MUOW), metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO). Neither BMI nor presence of the metabolic syndrome was associated with risk of colorectal cancer, whereas waist circumference showed a robust positive association. Relative to the MHNW phenotype, the MUNW phenotype was associated with increased risk, whereas no other phenotype showed an association. Furthermore, HOMA-IR was not associated with increased risk. Overall, our results do not support a direct role of metabolic dysregulation in the development of colorectal cancer; however, they do suggest that higher waist circumference is a risk factor, possibly reflecting the effects of increased levels of cytokines and hormones in visceral abdominal fat on colorectal carcinogenesis.
KW - Body mass index
KW - Colorectal cancer risk
KW - HOMA-IR
KW - Metabolic status
KW - Postmenopausal women
KW - Waist circumference
UR - http://www.scopus.com/inward/record.url?scp=85043694614&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85043694614&partnerID=8YFLogxK
U2 - 10.1002/ijc.31345
DO - 10.1002/ijc.31345
M3 - Article
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
ER -