Dietary Factors and Microsatellite Instability in Sporadic Colon Carcinomas

Brenda Diergaarde; Hanneke Braam; Goos N. P. van Muijen; Marjolijn J. L. Ligtenberg; Frans J. Kok; Ellen Kampman

DOI: Published November 2003

Article Figures & Data

Tables

Table 1

Characteristics of the study population

	Controls (n = 259)	Cases
	Controls (n = 259)			MSI-H (n = 40; 22%)	MSI-L/MSS (n = 144; 78%)	P^a
Age (in yrs, mean ± SD)	61.8 ± 10.0	61.9 ± 10.1	61.8 ± 10.4	0.97
Sex (% women)	47.5	45.0	45.8	0.93
Family history of colorectal cancer (%)	11.5	16.7	21.1	0.56
Body mass index (kg/m², mean ± SD)	26.0 ± 3.8	27.3 ± 5.4	25.5 ± 4.0	0.06
Ever smoked (%)	69.1	67.5	70.4	0.72
Dietary factors (g/day, mean ± SD)
Vegetables	207.9 ± 124.2	168.4 ± 75.4	170.6 ± 82.1	0.88
Fruit	230.8 ± 180.6	214.7 ± 167.1	214.6 ± 160.6	0.996
Red meat	73.9 ± 34.1	69.2 ± 38.0	81.1 ± 35.2	0.07
Fish	18.2 ± 21.2	20.2 ± 26.7	22.3 ± 33.8	0.72
Dairy products	268.2 ± 244.3	351.0 ± 337.4	322.5 ± 330.1	0.63
Alcohol^b	13.7 ± 17.6	18.7 ± 23.6	15.9 ± 25.3	0.53
Dietary fiber^b	28.8 ± 8.3	27.6 ± 10.0	27.0 ± 8.3	0.70
Calcium^b (mg/day)	1254.3 ± 406.3	1263.4 ± 436.9	1275.0 ± 424.4	0.88
Vitamin C^b (mg/day)	117.5 ± 53.8	93.5 ± 42.9	105.5 ± 53.8	0.19
Total energy intake (kJ/day)	9362 ± 2844	10783 ± 3762	10197 ± 3053	0.31
Tumor characteristics
Tumor location (% proximal)	n.a.^c	67.5	34.7	<0.01
TNM stage (% I/II)	n.a.	75.0	58.3	0.07

a MSI-H versus MSI-L/MSS, t test for continuous variables and χ² test for categorical variables.
b Adjusted for total energy intake by regression analysis, for women and men separately.
c n.a., not applicable.

Table 2

Dietary factors and MSI^a in sporadic colon carcinomas: case-control and case-case comparisons

	ORs (95% CIs)^b
		T1	T2	T3	P^trend	Continuous^c
Vegetables (g/day)	≤166	166–223	>223		/106
No. MSI-H/MSS/controls	20/70/87	12/45/87	8/29/85		40/144/259
All cases vs. controls	1.0	0.6 (0.4–1.0)	0.4 (0.2–0.6)	<0.01	0.6 (0.5–0.8)
MSI-H vs. controls	1.0	0.5 (0.2–1.2)	0.4 (0.1–0.9)	0.02	0.6 (0.4–0.9)
MSS vs. controls	1.0	0.7 (0.4–1.1)	0.4 (0.2–0.7)	<0.01	0.6 (0.5–0.8)
MSI-H vs. MSS	1.0	0.9 (0.4–2.0)	0.8 (0.3–2.2)	0.67	0.9 (0.6–1.5)
Fruit (g/day)	≤142	142–269	≥269		/164
No. MSI-H/MSS/controls	15/51/87	15/49/85	10/44/87		40/144/259
All cases vs. controls	1.0	0.9 (0.6–1.5)	0.7 (0.5–1.2)	0.22	0.9 (0.7–1.0)
MSI-H vs. controls	1.0	1.0 (0.4–2.3)	0.6 (0.2–1.4)	0.21	0.8 (0.6–1.2)
MSS vs. controls	1.0	0.9 (0.6–1.5)	0.8 (0.5–1.3)	0.40	0.9 (0.7–1.1)
MSI-H vs. MSS	1.0	1.1 (0.5–2.6)	0.7 (0.3–1.8)	0.47	0.9 (0.7–1.4)
Red meat (g/day)	<58	58–87	≥87		/43
No. MSI-H/MSS/controls	16/33/85	11/56/87	13/55/87		40/144/259
All cases vs. controls	1.0	1.3 (0.8–2.1)	1.2 (0.7–1.9)	0.60	1.1 (0.8–1.4)
MSI-H vs. controls	1.0	0.6 (0.3–1.5)	0.5 (0.2–1.2)	0.11	0.6 (0.4–1.0)
MSS vs. controls	1.0	1.6 (1.0–2.8)	1.5 (0.9–2.6)	0.19	1.2 (0.9–1.6)
MSI-H vs. MSS	1.0	0.3 (0.1–0.8)	0.3 (0.1–0.9)	0.03	0.5 (0.3–0.9)
Fish (g/day)	<7	7–19	>19		/20
No. MSI-H/MSS/controls	15/43/82	9/41/91	16/60/86		40/144/259
All cases vs. controls	1.0	0.8 (0.5–1.3)	1.1 (0.7–1.7)	0.62	1.1 (0.9–1.2)
MSI-H vs. controls	1.0	0.6 (0.2–1.5)	0.9 (0.4–1.9)	0.84	1.0 (0.7–1.3)
MSS vs. controls	1.0	0.8 (0.5–1.4)	1.2 (0.7–2.0)	0.43	1.1 (0.9–1.3)
MSI-H vs. MSS	1.0	0.6 (0.2–1.6)	0.6 (0.3–1.4)	0.27	0.9 (0.7–1.1)
Dairy products (g/day)	≤117	117–305	>305		/287
No. MSI-H/MSS/controls	12/45/87	12/48/86	16/51/86		40/144/259
All cases vs. controls	1.0	1.0 (0.6–1.6)	1.0 (0.6–1.6)	0.87	1.1 (0.9–1.4)
MSI-H vs. controls	1.0	0.9 (0.4–2.3)	1.1 (0.5–2.7)	0.70	1.2 (0.8–1.7)
MSS vs. controls	1.0	1.0 (0.6–1.6)	0.9 (0.5–1.6)	0.77	1.1 (0.9–1.4)
MSI-H vs. MSS	1.0	1.0 (0.4–2.5)	1.3 (0.5–3.2)	0.54	1.1 (0.8–1.5)
Alcohol^d (g/day)	<3.8	3.8–12.9	>12.9		/18.4
No. MSI-H/MSS/controls	12/57/86	10/31/87	18/56/86		40/144/259
All cases vs. controls	1.0	0.8 (0.5–1.3)	1.2 (0.7–1.9)	0.30	1.1 (1.0–1.4)
MSI-H vs. controls	1.0	1.2 (0.5–3.2)	1.9 (0.8–4.7)	0.13	1.2 (0.9–1.7)
MSS vs. controls	1.0	0.7 (0.4–1.2)	1.0 (0.6–1.8)	0.49	1.1 (0.9–1.4)
MSI-H vs. MSS	1.0	1.7 (0.6–4.6)	1.7 (0.7–4.1)	0.36	1.1 (0.9–1.4)
Dietary fiber^d (g/day)	<25	25–31	>31		/10.3
No. MSI-H/MSS/controls	17/69/86	11/32/87	12/43/86		40/144/259
All cases vs. controls	1.0	0.5 (0.3–0.8)	0.6 (0.4–1.0)	0.03	0.7 (0.6–1.0)
MSI-H vs. controls	1.0	0.8 (0.3–1.8)	0.7 (0.3–1.7)	0.48	0.8 (0.5–1.3)
MSS vs. controls	1.0	0.5 (0.3–0.8)	0.6 (0.3–1.0)	0.03	0.7 (0.5–0.9)
MSI-H vs. MSS	1.0	1.6 (0.6–3.9)	1.2 (0.5–2.9)	0.71	1.1 (0.7–1.8)
Calcium^d (mg/day)	≤1062	1062–1358	>1358		/458.3
No. MSI-H/MSS/controls	12/48/87	13/35/86	15/61/86		40/144/259
All cases vs. controls	1.0	0.9 (0.6–1.5)	1.3 (0.8–2.1)	0.22	1.0 (0.8–1.3)
MSI-H vs. controls	1.0	1.4 (0.6–3.4)	1.5 (0.6–3.5)	0.42	1.1 (0.7–1.5)
MSS vs. controls	1.0	0.8 (0.5–1.4)	1.3 (0.8–2.2)	0.24	1.0 (0.8–1.3)
MSI-H vs. MSS	1.0	1.8 (0.7–4.5)	1.1 (0.4–2.6)	0.99	1.0 (0.7–1.5)
Vitamin C^d (mg/day)	≤89	89–133	>133		/68.5
No. MSI-H/MSS/controls	17/62/87	18/49/86	5/33/86		40/144/259
All cases vs. controls	1.0	0.9 (0.5–1.4)	0.5 (0.3–0.8)	<0.01	0.7 (0.5–0.9)
MSI-H vs. controls	1.0	1.2 (0.5–2.5)	0.3 (0.1–0.8)	0.03	0.5 (0.3–0.8)
MSS vs. controls	1.0	0.8 (0.5–1.3)	0.5 (0.3–0.9)	0.02	0.7 (0.6–1.0)
MSI-H vs. MSS	1.0	1.3 (0.6–2.9)	0.5 (0.2–1.6)	0.38	0.7 (0.4–1.2)

a The subset MSI-L/MSS is, for brevity, called MSS in this table.
b Adjusted for age, sex, body mass index, and total energy intake. Alcohol is additionally adjusted for cigarette smoking. Trend was assessed using the median values of the tertiles as continuous variables.
c Per interquartile range (Q₃ to Q₁).
d Adjusted for total energy intake by regression analysis, for women and men separately.

Table 3

Expression of hMLH1 and hMSH2 and hMLH1 promoter methylation status^a N (%)

	All tumors (n = 184)	MSI-H (n = 40)	MSI-L/MSS (n = 144)	Hypermethylation
	All tumors (n = 184)	MSI-H (n = 40)	MSI-L/MSS (n = 144)			Yes (n = 20)	No (n = 17)
hMLH1 absent	26 (14)	26 (65)	0	17 (85)	7 (41)
hMSH2 absent	6 (3)	6 (15)	0	0	6 (35)
hMLH1 and hMSH2 present	152 (83)	8 (20)	144 (100)	3 (15)	4 (24)