Table 3

Genotypes of QUASAR2 individuals with grade 4 toxicity at selected DPYD variants

Case	D	V	H	N	P	M	S	Possible explanation	2846	*2A	A551T	*13	*4	*5	*9A	M166V	K259E	rs12132152	rs12022243	rs2612091
1	4	0	2	0	0	0	0		0	0	0	0	0		0	0	0	0	0	2
2	4	0	0	0	0	0	0		0	0	0	0	0	0	0	0	0	0	1	2
3	0	4	0	0	0	0	0		0	0	0	0	1	1	0	0	0	0	1	1
4	4	2	2	0	0	0	0		0	0	0	0	0	0	2	1	0	0	0	0
5	4	0	0	0	0	0	1	2846T>A	1	0	0	0	1	1	0	0	0	0	0	0
6	2		1	4	4	0	2	2846T>A	1	0	0	0	1	0	0	0	0	0	2	1
7	3	0	2	4	4	3	3	A551T	0	0	1	0	0	0	0	0	0	0	1	2
8	3	1	3	4	2	3	3		0	0	0	0	0	2	0	0	0	0	1	2
9	4	0	2	0	0	1	0		0	0	0	0	1	0	0	0	0	0	1	2
10	4	1	3	0	0	1	0		0	0	0	0	0	0	0	0	0	0	1	2
11	4	2	1	1	0	0	0		0	0	0		0	1	0	0		0	1	2
12	0	0	3	4	4	3	3	*2A	0	1	0	0	0	0	1	1	0	0	0	1
13	4	0	1	0	1	1	1		0	0	0	0	0	1	0	0	0	0	1	1
14	0	4	3	0	1	0	0		0	0	0	0	0	0	1	1	0	0	1	2
15	4	0	1	0	0	1	1		0	0	0	0	0	1	0	0	0	0	0	1
16	4	0	2	0	0	0	0		0	0	0	0	0	0	0	0	0	0	1	1
17	1	0	4	0	0	0	0		0		0	0	0	0	0	0	0	0	1	0
18	2	4	3	0	0	0	1		0	0	0	0	0	1	0	0	0	0	0	0
19	3	0	2	4	4	0	4	*13	0	0	0	1	0				0

The variants shown are (1) those identified by this study (rs12132152, rs12022243, rs2612091, DPYD A551 T), (2) DPYD alleles (2846 A>T and *2A) shown to be associated with 5-FU toxicity in the meta-analysis of Rosmarin et al7 and (3) potential DPYD toxicity alleles from Caudle et al.8 Genotypes shown are major allele homozygote (0), heterozygote (1) and minor or variant allele homozygote (2). Blank cells denote missing data. The allele that provides a plausible explanation for the severe toxicity is shown. Note that *4 and *5 DPYD alleles are in complete linkage disequilibrum (D’=1.0) with 2A or 2846T>A. Overall association statistics and genotype frequencies in cases and controls are shown for the analysis of binary global toxicity in online supplementary table S3.
For the toxicities, D=diarrhoea; H=HFS; M=mucositis; N=neutropaenia; P=thrombocytpaenia; S=stomatitis; V=vomiting.