Case-control study of overweight, obesity, and colorectal cancer risk, overall and by tumor microsatellite instability status.
BACKGROUND
Being overweight or obese is an established risk factor for colorectal cancer, more so for men than for women. Approximately 10%-20% of colorectal tumors display microsatellite instability (MSI), defined as the expansion or contraction of small repeated sequences in the DNA of tumor tissue relative to nearby normal tissue. We evaluated associations between overweight or obesity and colorectal cancer risk, overall and by tumor MSI status.


METHODS
The study included 1794 case subjects with incident colorectal cancer who were identified through population-based cancer registries and 2684 of their unaffected sex-matched siblings as control subjects. Recent body mass index (BMI), BMI at age 20 years, and adult weight change were derived from self-reports of height and weight. Tumor MSI status, assessed at as many as 10 markers, was obtained for 69.7% of the case subjects and classified as microsatellite (MS)-stable (0% of markers unstable; n = 913), MSI-low (>0% but <30% of markers unstable; n = 149), or MSI-high (> or =30% of markers unstable; n = 188). Multivariable conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). All statistical tests were two-sided.


RESULTS
Recent BMI, modeled in 5 kg/m(2) increments, was positively associated with risk of colorectal cancer for men and women combined (OR = 1.24; 95% CI = 1.15 to 1.34), for women only (OR = 1.20; 95% CI = 1.10 to 1.32), and for men only (OR = 1.30; 95% CI = 1.15 to 1.47). There was no interaction with sex (P = .22). Recent BMI, per 5 kg/m(2), was positively associated with the risk of MS-stable (OR = 1.38; 95% CI = 1.24 to 1.54) and MSI-low (OR = 1.33; 95% CI = 1.04 to 1.72) colorectal tumors, but not with the risk of MSI-high tumors (OR = 1.05; 95% CI = 0.84 to 1.31).


CONCLUSIONS
The increased risk of colorectal cancer associated with a high BMI might be largely restricted to tumors that display the more common MS-stable phenotype, suggesting further that colorectal cancer etiology differs by tumor MSI status.
Campbell
Peter T
PT
Epidemiology Research Program, American Cancer Society, National Home Office, 250 Williams St NW, Atlanta, GA 30303, USA. peter.campbell@cancer.org.
Jacobs
Elizabeth T
ET
Ulrich
Cornelia M
CM
Figueiredo
Jane C
JC
Poynter
Jenny N
JN
McLaughlin
John R
JR
Haile
Robert W
RW
Jacobs
Eric J
EJ
Newcomb
Polly A
PA
Potter
John D
JD
Le Marchand
Loïc
L
Green
Roger C
RC
Parfrey
Patrick
P
Younghusband
H Banfield
HB
Cotterchio
Michelle
M
Gallinger
Steven
S
Jenkins
Mark A
MA
Hopper
John L
JL
Baron
John A
JA
Thibodeau
Stephen N
SN
Lindor
Noralane M
NM
Limburg
Paul J
PJ
Martínez
María Elena
ME
D000328:Adult; D001741:Black or African American / Q000235:genetics / Q000706:statistics & numerical data; D000368:Aged; D015992:Body Mass Index; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000208:ethnology / Q000209:etiology* / Q000235:genetics; D015986:Confounding Factors, Epidemiologic; D005260:Female; D006801:Humans; D007198:Indians, North American / Q000235:genetics / Q000706:statistics & numerical data; D008019:Life Style; D016015:Logistic Models; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D015999:Multivariate Analysis; D009765:Obesity / Q000150:complications; D016017:Odds Ratio; D050177:Overweight / Q000150:complications*; D018570:Risk Assessment; D012307:Risk Factors; D015430:Weight Gain; D044465:White People / Q000235:genetics / Q000706:statistics & numerical data