Diet, physical activity, and body size associations with rectal tumor mutations and epigenetic changes.
Diet and lifestyle factors have been inconsistently associated with rectal tumors. It is possible that evaluation of specific tumor markers with these factors may help clarify these associations. In this study, we examine energy contributing nutrients, dietary fiber, BMI (kg/m2), and long-term physical activity with TP53 mutations, KRAS2 mutations, and CpG Island Methylator Phenotype (CIMP) in 750 population-based cases of rectal cancer compared to healthy controls. We observed that high levels of physical activity reduced the risk of having TP53 and KRAS2 rectal tumor mutations. Dairy products rich in fat were associated with an increased risk of CIMP+ tumors (OR 1.88 95% CI 0.92, 3.84), while low-fat dairy products reduced risk of CIMP+ tumors (OR 0.56 95% CI 0.29, 1.09). Omega-3 fatty acids were associated with a twofold increased risk of a CIMP+ tumor. High levels of vegetable intake reduced risk of both TP53 mutations (OR 0.73 95% CI 0.54, 1.00; p trend 0.02) and KRAS2 mutations (OR 0.60 95% CI 0.40, 0.89; p trend <0.01). High intake of whole grains reduced the likelihood of a TP53 mutation (OR 0.74 95% CI 0.56, 0.99), while high intake of refined grains increased the likelihood of a TP53 mutation (OR 1.41 95% CI 1.02, 1.96). Dietary fiber also was associated with reduced risk of TP53 and KRAS2 rectal tumor mutations. Overall, a prudent dietary pattern significantly reduced the likelihood of a KRAS2 tumor mutation (OR 0.68 95% CI 0.47, 0.98; p linear trend 0.03). These data suggest that diet and lifestyle factors are associated with specific types of rectal tumor mutations and epigenetic changes. Findings need confirmation in other studies.
Slattery
Martha L
ML
Department of Medicine, University of Utah, Salt Lake City, UT 84108, USA. marty.slattery@hsc.utah.edu
Curtin
Karen
K
Wolff
Roger K
RK
Herrick
Jennifer S
JS
Caan
Bette J
BJ
Samowitz
Wade
W
D000328:Adult; D000368:Aged; D049628:Body Size; D004032:Diet; D044127:Epigenesis, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008019:Life Style; D008297:Male; D008875:Middle Aged; D009043:Motor Activity; D009154:Mutation; D012004:Rectal Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D012307:Risk Factors
Eur J Cancer. 2006 Oct;42(15):2590-7
16914307
Comput Methods Programs Biomed. 2007 Sep;87(3):262-9
17686544
Cancer Causes Control. 1997 Jul;8(4):575-90
9242473
Am J Epidemiol. 2003 Aug 1;158(3):214-24
12882943
J Am Diet Assoc. 1991 Sep;91(9):1104-12
1918764
Gastroenterology. 2005 Sep;129(3):837-45
16143123
Int J Cancer. 2004 Sep 20;111(5):750-6
15252846
J Am Diet Assoc. 1994 Jul;94(7):761-6
8021418
Ann Epidemiol. 1997 Feb;7(2):137-45
9099401
Stat Med. 1998 Jun 15;17(11):1261-91
9670414
Ann Epidemiol. 1995 Jul;5(4):292-6
8520711
Colorectal Dis. 2009 Sep;11(7):689-701
19207713
Am J Pathol. 2003 Mar;162(3):815-22
12598316
J Natl Cancer Inst. 2000 Nov 1;92(21):1740-52
11058617
Am J Epidemiol. 1994 Dec 1;140(11):1020-8
7985650
Cancer Causes Control. 2007 Oct;18(8):865-79
17636402
Cancer Epidemiol Biomarkers Prev. 2006 Dec;15(12):2398-407
17164362
Gastroenterology. 2005 Sep;129(3):1121-4
16143149
Am J Clin Nutr. 2004 Feb;79(2):274-81
14749234
Am J Epidemiol. 1998 Jul 1;148(1):4-16
9663397
Int J Cancer. 2001 Aug 15;93(4):601-7
11477566
J Natl Cancer Inst. 2006 Dec 6;98(23):1731-8
17148775
Cancer Causes Control. 2004 Nov;15(9):863-72
15577288
Eur J Cancer Prev. 2008 Jun;17(3):201-8
18414190
Int J Cancer. 2009 Oct 1;125(7):1698-704
19452524
Cancer Res. 2000 Dec 15;60(24):6935-41
11156393
Dan Med Bull. 1987 Oct;34(5):267-74
3315476
Ethn Dis. 1994 Winter;4(1):15-27
7742729
Am J Epidemiol. 2000 Dec 1;152(11):1081-92
11117618
Nutr Cancer. 2003;46(2):166-71
14690792
Cancer Causes Control. 2008 Nov;19(9):939-53
18437512
J Nutr. 2004 Apr;134(4):776-84
15051825
Cancer Epidemiol Biomarkers Prev. 2002 Jun;11(6):541-8
12050095
Cancer Epidemiol Biomarkers Prev. 1998 Feb;7(2):163-8
9488592
J Natl Cancer Inst. 2000 Nov 15;92(22):1831-6
11078760
Int J Cancer. 2007 Feb 1;120(3):656-63
17096326
Int J Cancer. 2007 Dec 1;121(11):2373-80
17893866
Int J Cancer. 2003 Jul 20;105(6):831-7
12767070
Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):143-8
12518062
Eur J Cancer Prev. 2002 Aug;11(4):369-75
12195164
Cancer Res. 1997 Jan 1;57(1):75-80
8988044
Cancer Res. 2003 Aug 15;63(16):4805-8
12941799
Nutr Cancer. 2002;43(1):39-46
12467133