Table 4. Evaluation in 329 MMR mutation carriers with CRC of the risk associated with 8q23.3, 11q23.1, 18q21, CYP1A1 and IGF1 variants.

		Total sample (N=329)				Males (N=177)				Females (N=152)
Locus	Genotype	N	Hazard ratioa	95% CI	Pb	N	HR	95% CI	Pb	N	HR	95% CI	Pb
8q23.3	rs16892766
	AA	277	1			142	1			135	1
	AC	50	0.793	0.559–1.124	0.1920	34	0.768	0.478–1.234	0.2749	16	0.833	0.5041.376	0.4759
	CC	2	/	/	<0.0001	1	/	/	<0.0001	1	/	/	<0.0001
					<0.0001				<0.0001				<0.0001
	Per allele		0.666	0.481–0.922	0.0144		0.647	0.414–1.009	0.0549		0.698	0.443–0.102	0.1227
11q23.1	rs3802842
	AA	167	1			90	1			77	1
	AC	139	0.941	0.738–1.199	0.6216	71	0.840	0.593–1.191	0.3274	68	1.067	0.751–1.515	0.7180
	CC	23	1.234	0.694–2.195	0.4736	16	1.034	0.548–1.950	0.9182	7	1.815	0.664–4.963	0.2457
					0.6151				0.5740				0.5057
	Per allele		1.028	0.831–1.272	0.9763		0.947	0.723–1.239	0.947		1.170	0.854–1.604	0.3289
18q21	Novel 1
	CC	72	1			45	1			27	1
	CG	165	0.828	0.588–1.166	0.2804	87	1.081	0.701–1.667	0.7249	78	0.571	0.315–1.035	0.0647
	GG	95	0.741	0.516–1.062	0.1029	45	0.867	0.554–1.358	0.5326	47	0.570	0.305–1.068	0.0793
					0.2637				0.5573				0.1637
	Per allele		0.865	0.726–1.031	0.1056		0.919	0.735–1.149	0.4607		0.796	0.595–1.065	0.1238
CYP1A1	rs1048943
	AA	313	1			168	1			145	1
	AG	16	1.107	0.609–2.011	0.7387	9	1.105	0.502–2.432	0.8045	7	1.110	0.447–2.754	0.8224
	GG	0	/	/	/	0	/	/	/	0	/	/	/
					0.7387				0.8045				0.8224
	Per allele		1.107	0.609–2.011	0.7387		1.105	0.502–2.432	0.8045		1.110	0.447–2.754	0.8224
CYP1A1	rs4646903
	TT	265	1			143	1			122	1
	TC	61	0.988	0.725–1.348	0.9412	32	1.070	0.696–1.647	0.7568	29	0.902	0.572–1.421	0.6558
	CC	3	1.741	0.925–3.278	0.0856	2	2.276	0.890–5.822	0.0861	1	1.241	0.759–2.029	0.3895
					0.2094				0.2291				0.5036
	Per allele		1.038	0.786–1.372	0.7919		1.139	0.773–1.678	0.5117		0.930	0.618–1.399	0.7277
IGF1	CA repeat
	≥18;≥18	314	1			166	1			148	1
	≥18; ≤17	15	0.710	0.397–1.272	0.2502	11	0.562	0.297–1.063	0.0765	4	1.709	0.470–6.212	0.4160

^aHazard ratio relative to subjects not carrying the SNP on either allele for each of the five SNPs considered or to subjects with CA repeat length greater than or equal to 18 on both alleles for the IGF1 promoter and obtained from Cox proportional hazard regression stratified on gender (if applicable), mutated MMR gene (MSH2, MLH1, MSH6) and year of birth (<1940, 1940–1949, 1950–1959, 1960–1969, 1970–1979 and ≥1980), and with control for familial aggregation. The per-allele value refers to Cox regression with a trend fitted for number of alleles carrying the SNP (0, 1, 2).

^bFor each of the five SNP variants and each sample (total sample, males, females), the first two P-values refer to separate comparisons of heterozygous and homozygous subjects for the SNPs considered, with subject not presenting the SNP on either allele; the third P-value refers to the overall comparison of heterozygous, homozygous and SNP-free subjects (heterogeneity test); the final P-value refers to the assessment of the trend for the number of alleles carrying the SNP (0, 1, 2). For IGF1 CA repeat length, the P-value refers to the comparison of subjects with CA repeat length less than or equal to 17 on one allele to subjects with CA repeat length greater than or equal to 18 on both alleles. All tests are Wald tests.