Red Meat Intake, CYP2E1 Genetic Polymorphisms, and Colorectal Cancer Risk

DOI: Published October 2002

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Fig. 1.
Representative gel showing the three genotypes for the CYP2E1 insert. Lanes 0 show subjects with no insert. The product is 852-bp long. Lanes 2 show individuals with two inserts. The product is 948-bp long. Lanes 1 show individuals heterozygous for the insert with the 852- and 948-bp products. Lanes M, a pGEM DNA size marker (Promega).

Table 1

CRC ORs^a and CIs for the CYP2E1 RsaI and insert polymorphisms

CYP2E1			All			Colon
RsaI	c1/c1	384/449^b	1.0	271/449	1.0	120/449	1.0
	c1/c2	116/164	0.8 (0.6–1.1)	78/164	0.8 (0.6–1.1)	42/164	0.9 (0.6–1.3)
	c2/c2	21/26	0.9 (0.5–1.6)	19/26	1.2 (0.6–2.2)	3/26	0.4 (0.1–1.3)
			P = 0.20^c		P = 0.48		P = 0.22
	any c2	137/190	0.8 (0.6–1.1)	97/190	0.8 (0.6–1.1)	45/190	0.8 (0.6–1.3)
Insert	0	357/468	1.0	261/468	1.0	104/468	1.0
	1	133/137	1.3 (1.0–1.8)	88/137	1.2 (0.9–1.7)	49/137	1.7 (1.1–2.6)
	2	21/32	0.9 (0.5–1.6)	12/32	0.7 (0.3–1.2)	9/32	1.4 (0.6–3.1)
			P = 0.34		P = 0.99		P = 0.55
	1 or 2	154/169	1.3 (0.9–1.7)	100/169	1.1 (0.8–1.5)	58/169	1.6 (1.1–2.5)

^a Adjusted by unconditional logistic regression for age, sex, ethnicity, pack-years of cigarette smoking, lifetime recreational physical activity (hours), lifetime aspirin use (months), body mass index 5 years ago, years of schooling, and intakes of nonstarch polysaccharides from vegetables and calcium from foods and supplements.
^b No. of cases/no. of controls. The CYP2E1 insert genotype was missing for 10 cases and 2 controls for whom DNA was depleted. Twelve cases had multiple colorectal tumors involving both colon and rectum, and these cases were included in both subsite models.
^c P for gene-dosage effect.

Table 2

Joint effects of CYP2E1 and RM and PM intakes on CRC risk

Subsite	CYP2E1			RM (g/day) (without processed meats)^a									PMs (g/day)^b
						≤Median			>Median			P^c	≤Median			>Median	P
						n^c	OR^d (95% CI)	n	OR (95% CI)		n	P^c	OR (95% CI)	n	OR (95% CI)		P
Colon	RsaI	c1/c1	118/217	1.0	153/232	1.1 (0.8–1.5)		107/221	1.0	164/228	1.4 (1.0–1.9)
		Any c2	56/98	1.1 (0.7–1.6)	41/92	0.8 (0.5–1.2)	0.18	43/102	0.9 (0.6–1.4)	54/88	1.2 (0.6–1.4)	0.81
	Insert	0	126/229	1.0	135/239	0.9 (0.7–1.3)		101/234	1.0	160/234	1.4 (1.0–2.0)
		1 or 2	43/86	0.9 (0.6–1.4)	57/83	1.1 (0.7–1.7)	0.28	43/87	1.1 (0.7–1.8)	57/82	1.5 (0.9–2.3)	0.79
Rectum	RsaI	c1/c1	44/217	1.0	76/232	1.3 (0.8–2.0)		38/221	1.0	82/228	1.7 (1.0–2.6)
		Any c2	21/98	1.0 (0.5–1.8)	24/92	1.1 (0.6–1.9)	0.64	14/102	0.8 (0.4–1.6)	31/88	1.6 (0.9–2.9)	0.66
	Insert	0	44/229	1.0	60/239	1.1 (0.7–1.7)		35/234	1.0	69/234	1.5 (0.9–2.4)
		1 or 2	20/86	1.3 (0.7–2.5)	38/83	2.1 (1.2–3.7)	0.30	16/87	1.3 (0.6–2.5)	42/82	3.1 (1.8–5.6)	0.22

^a All beef, pork, veal, and lamb items, except PMs. Median intake: 37.4 g/day.
^b Ham, bacon, sausage, and luncheon meats. Median intake: 14.8 g/day.
^c No. of cases/no. of controls.
^d ORs (and 95% CIs) adjusted by unconditional logistic regression for age, sex, ethnicity, pack-years of cigarette smoking, lifetime recreational physical activity (hours), lifetime aspirin use (months), body mass index 5 years ago, years of schooling, and intakes of nonstarch polysaccharides from vegetables and calcium from foods and supplements.
^e P for interaction based on the likelihood ratio test comparing the model with interaction with one containing only main effects for the two variables (test has 1 degree of freedom).

Table 3

Joint effects of CYP2E1 and salted/dried fish and oriental pickled vegetable intakes on CRC risk

Subsite	CYP2E1			Salted/dried fish (g/day)^a							P^e	Oriental pickled vegetables (g/day)^b
						0			>0					≤Median		>Median
						n^c	OR^d (95% CI)	n	OR (95% CI)			n	OR (95% CI)	n	OR (95% CI)
Colon	RsaI	c1/c1	228/386	1.0	43/63	1.1 (0.7–1.8)		105/229	1.0	166/220	1.7 (1.2–2.4)
		Any c2	79/166	0.8 (0.6–1.1)	18/24	1.6 (0.8–3.0)	0.21	41/95	1.0 (0.6–1.6)	56/95	1.4 (0.9–2.1)	0.48
	Insert	0	217/402	1.0	44/66	1.3 (0.8–2.0)		100/237	1.0	161/231	1.7 (1.2–2.3)
		1 or 2	84/148	1.0 (0.7–1.5)	16/21	1.5 (0.7–2.0)	0.88	42/87	1.1 (0.7–1.7)	58/82	1.7 (1.1–2.7)	0.94
Rectum	RsaI	c1/c1	96/386	1.0	24/63	1.5 (0.9–2.6)		42/229	1.0	78/220	1.9 (1.2–3.0)
		Any c2	38/166	0.9 (0.6–1.4)	7/24	1.1 (0.4–2.9)	0.74	15/95	0.9 (0.5–1.8)	30/95	1.6 (0.9–2.9)	0.88
	Insert	0	87/402	1.0	17/66	1.1 (0.6–2.0)		38/237	1.0	66/231	1.7 (1.1–2.7)
		1 or 2	45/148	1.5 (1.0–2.4)	13/21	3.0 (1.4–6.6)	0.26	18/87	1.4 (0.7–2.6)	40/82	3.2 (1.8–5.7)	0.40

^a Salted and dried fish, including taegu.
^b Includes tsukemono, kim chee, and other Oriental pickled vegetables. Median intake: 1.64 g/day.
^c No. of cases/no. of controls.
^d ORs (and 95% CIs) adjusted by unconditional logistic regression for age, sex, ethnicity, pack-years of cigarette smoking, lifetime recreational physical activity (hours), lifetime aspirin use (months), body mass index 5 years ago, years of schooling, and intakes of nonstarch polysaccharides from vegetables and calcium from foods and supplements.
^e P for interaction based on the likelihood ratio test comparing the model with interaction with one containing only main effects for the two variables (test has 1 degree of freedom).

Table 4

Joint effects of CYP2E1, PM, and fruit and vegetable intake on CRC risk

Subsite	CYP2E1			Intakes (g/day) of fruits and vegetables and PMs^a
						High F&V, low PM			Low F&V, high PM	P^d
						n^b	OR^c (95% CI)	n	OR (95% CI)	P^d
Colon	RsaI	c1/c1	35/114	1.0	86/118	2.3 (1.4–3.9)
		Any c2	20/49	1.5 (0.8–3.1)	20/45	1.4 (0.7–2.9)	0.05
	Insert	0	38/117	1.0	80/123	1.9 (1.2–3.1)
		1 or 2	16/44	1.3 (0.6–2.6)	26/40	2.1 (1.0–4.0)	0.69
Rectum	RsaI	c1/c1	19/114	1.0	46/118	2.3 (1.2–4.4)
		Any c2	7/49	1.0 (0.4–2.9)	14/45	1.7 (0.7–3.9)	0.60
	Insert	0	18/117	1.0	32/123	1.7 (0.8–3.3)
		1 or 2	8/44	1.6 (0.6–4.3)	28/40	5.0 (2.2–11.4)	0.27

^a High F&V, low PM, fruit and vegetable intake > median (684 g/day) and PM intake ≤ median (14.8 g/day). Low F&V, high PM, fruit and vegetables intake ≤ median and processed meat intake > median.
^b No. of cases/no. of controls.
^c ORs (and 95% CIs) adjusted by unconditional logistic regression for age, sex, ethnicity, pack-years of cigarette smoking, lifetime recreational physical activity (hours), lifetime aspirin use (months), body mass index 5 years ago, years of schooling, and intake of calcium from foods and supplements.
^d P for interaction based on the likelihood ratio test comparing the model with interaction with one containing only main effects for the two variables (test has 1 degree of freedom).