Table 3. Evaluation in 748 MMR mutation carriers of the CRC risk associated with 8q23.3, 11q23.1, 18q21, CYP1A1 and IGF1 variants.

		Total sample (N=748)					Males (N=349)					Females (N=399)
Locus	Genotype	N	CRC cases	Hazard ratioa	95% CI	Pb	N	CRC Cases	HR	95% CI	Pb	N	CRC cases	HR	95% CI	Pb
8q23.3	rs16892766
	AA	641	277	1			290	142	1			351	135	1
	AC	104	50	1.184	0.866–1.617	0.2892	57	34	1.266	0.836–1.916	0.2656	47	16	1.067	0.677–1.680	0.7802
	CC	3	2	0.267	0.083–0.861	0.0271	2	1	0.460	0.301–0.701	0.0003	1	1	/	/	<0.0001
						0.0462					0.0002					<0.0001
	Per allele			1.032	0.778–1.368	0.8283			1.117	0.770–1.621	0.5602			0.899	0.575–1.405	0.6397
11q23.1	rs3802842
	AA	380	167	1			178	90	1			202	77	1
	AC	321	139	0.923	0.725–1.176	0.5165	141	71	0.844	0.611–1.167	0.3047	180	68	1.019	0.723–1.438	0.9125
	CC	47	23	1.107	0.684–1.791	0.6793	30	16	1.043	0.599–1.815	0.8814	17	7	1.222	0.543–2.750	0.6284
						0.6491					0.5079					0.8891
	Per allele			0.988	0.806–1.210	0.9058			0.947	0.735–1.220	0.6740			1.052	0.778–1.422	0.7428
18q21	Novel 1
	CC	156	72	1			84	45	1			72	27	1
	CG	395	165	0.956	0.704–1.296	0.7702	185	87	1.021	0.675–1.546	0.9215	210	78	0.865	0.546–1.370	0.5359
	GG	197	92	1.006	0.727–1.390	0.9729	80	45	1.088	0.706–1.677	0.7007	117	47	0.903	0.564–1.447	0.6714
						0.9001					0.9087					0.8249
	Per allele			1.007	0.859–1.181	0.9326			1.044	0.841–1.295	0.6962			0.964	0.765–1.215	0.7570
CYP1A1	rs1048943
	AA	708	313	1			331	168	1			377	145	1
	AG	40	16	1.026	0.601–1.752	0.9249	18	9	0.930	0.444–1.948	0.8480	22	7	1.168	0.583–2.338	0.6619
	GG	0	0	/	/	/	0	0	/	/	/	0	0	/	/	/
						0.9249					0.8480					0.6619
	Per allele			1.026	0.601–1.752	0.9249			0.930	0.444–1.948	0.8480
CYP1A1	rs4646903
	TT	598	265	1			279	143	1			319	122	1
	TC	140	61	1.031	0.769–1.382	0.8400	66	32	0.909	0.601–1.375	0.6524	74	29	1.198	0.789–1.818	0.3956
	CC	10	3	1.163	0.387–3.495	0.7882	4	2	3.496	1.517–8.057	0.0033	6	1	0.507	0.071–3.640	0.4997
						0.9441					0.0090					0.5434
	Per allele			1.039	0.801–1.347	0.7730			1.001	0.680–1.474	0.9948			1.079	0.746–1.561	0.6874
IGF1	CA repeat
	≥18;≥18	710		1			329		1			381		1
	≥18; ≤17	38		0.731	0.447–1.196	0.2127	20		0.662	0.372–1.179	0.1611	18		0.979	0.450–2.132	0.9579

^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.