Age-associated Risk of Cancer among Individuals with N-Acetyltransferase 2 (NAT2) Mutations and Mutations in DNA Mismatch Repair Genes

Marsha L. Frazier; Frederick T. O’Donnell; Shouming Kong; Xiangjun Gu; Imelda Campos; Rajyalakshmi Luthra; Patrick M. Lynch; Christopher I. Amos

DOI: Published February 2001

Article Figures & Data

Tables

Table 1
Genotype analysis of 86 patients with mutations in MMR genes at each of three NAT2 loci

NAT2 locus WT/WT^a WT/M^b M/M Total N^c
NAT2*5 q^d = 0.34 (56/168) 39 34 11 84
NAT2*6 q = 0.30 (51/170) 44 31 10 85
NAT2*7 q = 0.07 (11/168) 73 11 0 84

a WT, wild type at NAT2 locus indicated in first column.

b M, mutant at NAT2 locus indicated in first column.

c Not equal to total number of subjects because we were unable to obtain genotypes for some. All of the subjects that were genotyped for each locus are presented in this table including both affected and unaffected subjects.

d q, allele frequency.

Table 2

Median time to diagnosis (years) for CRC and all of the cancers for all of the subjects stratified by NAT2 genotype and number of affected individuals^a

Cancer	NAT2 locus	(WT/WT^b)	(WT/M^c)	(M/M)
CRC	NAT25*	50.0 (n = 21)	48.0 (n = 22)	36.0 (n = 5)
	NAT26*	47 (n = 24)	57.1 (n = 17)	46.7 (n = 8)
	NAT27*	53.6 (n = 42)	46.7 (n = 6)	(n = 0)
All cancers	NAT25*	48.0 (n = 25)	48.0 (n = 22)	43.0 (n = 6)
	NAT26*	42.0 (n = 27)	57.0 (n = 19)	42.0 (n = 8)
	NAT27*	48.0 (n = 46)	39.5 (n = 7)	(n = 0)

a n, number of affected individuals.
b WT, wild type at NAT2 locus indicated in second column.
c M, mutant at NAT2 locus indicated in second column.

Table 3

Cox proportional hazard regression of risk of CRC and cancer stratified by NAT2 genotype

	Univariate results				Multivariate results (adjusted by NAT25, NAT26, and NAT2*7)
	HR	95% CI-L^a	95% CI-U^b	P	HR	95% CI-L	95% CI-U	P
CRC
NAT2*5 (wt^c/wt)	1				1
NAT2*5 (wt/m^d)	1.70	0.969	2.985	0.0640	2.38	1.332	4.251	0.0034
NAT2*5 (m/m)	1.20	0.388	3.691	0.7600	1.6	0.495	5.181	0.4300
NAT2*6 (wt/wt)	1				1
NAT2*6 (wt/m)	0.62	0.351	1.086	0.0940	0.75	0.415	1.350	0.3300
NAT2*6 (m/m)	0.94	0.368	2.370	0.8900	1.82	0.586	5.674	0.3000
NAT2*7 (wt/wt)	1				1
NAT2*7 (wt/m)	2.10	0.989	4.475	0.0530	2.96	1.280	6.854	0.0120
NAT2*7 (m/m)
Cancer
NAT2*5 (wt/wt)	1				1
NAT2*5 (wt/m)	1.22	0.686	2.163	0.5000	1.34	0.730	2.460	0.3500
NAT2*5 (m/m)	1.1	0.435	2.776	0.8400	1.13	0.409	3.106	0.8200
NAT2*6 (wt/wt)	1				1
NAT2*6 (wt/m)	0.59	0.340	1.031	0.0640	0.63	0.327	1.216	0.1700
NAT2*6 (m/m)	0.7	0.266	1.823	0.4600	0.94	0.300	2.948	0.9200
NAT2*7 (wt/wt)	1				1
NAT2*7 (wt/m)	2.82	1.761	4.546	0.00001	3.37	1.918	5.909	0.00004
NAT2*7 (m/m)