Polymorphism AGT2 (rs4762) is involved in the development of dermatologic events: Proof-of-concept in hepatocellular carcinoma patients treated with sorafenib

Table 5 Cox regression models for eDAE and DAE by AGT2 (rs4762)

Event	Center	AGT2(rs4762)	HR (95%CI)	P value	HR (95%CI) adjusted for BCLC + ECOG-PS	P value	HR (95%CI) adjusted for BCLC + ECOG-PS + AHT + DM	P value	HR (95%CI) adjusted for AHT + DM	P value	HR (95%CI) adjusted for DM	P value	HR (95%CI) adjusted for AHT	P value
eDAE	BCLC1 cohort	AA vs AG	1.14 (0.22-5.89)	0.9	0.98 (0.19-5.12)	0.9	0.97 (0.18-5.04)	0.9	1.09 (0.21-5.64)	0.9	1.15 (0.22-5.95)	0.9	1.11 (0.21-5.72)	0.9
		AA vs GG	0.84 (0.2-3.53)	0.8	0.73 (0.17-3.15)	0.7	0.71 (0.16-3.1)	0.7	0.81 (0.19-3.4)	0.8	0.8 (0.19-3.39)	0.8	0.84 (0.2-3.54)	0.8
		AG vs GG	0.73 (0.28-1.91)	0.5	0.74 (0.28-1.94)	0.5	0.74 (0.28-1.97)	0.6	0.74 (0.28-1.94)	0.6	0.7 (0.27-1.82)	0.5	0.76 (0.29-1.98)	0.6
	BCLC2 cohort	AA vs AG	3.71 (0.62-22.39)	0.2	3.52 (0.58-21.5)	0.2	4.8 (0.74-31.28)	0.1	4.81 (0.74-31.24)	0.1	4.78 (0.76-29.88)	0.09	4.46 (0.7-28.35)	0.11
		AA vs GG	4.43 (1.01-19.39)	0.048	4.24 (0.95-19.06)	0.06	6.14 (1.28-29.55)	0.02	6.28 (1.32-29.95)	0.02	6.25 (1.35-28.89)	0.02	5.34 (1.15-24.86)	0.03
		AG vs GG	1.19 (0.35-4.08)	0.8	1.21 (0.35-4.15)	0.8	1.28 (0.37-4.45)	0.7	1.31 (0.38-4.47)	0.7	1.31 (0.38-4.47)	0.7	1.2 (0.35-4.08)	0.8
	Northern Italy cohort	AA vs AG	2.72 (0.57-13.1)	0.2	3.21 (0.64-15.99)	0.15	5.61 (1.01-31.12)	0.048	3.43 (0.69-16.96)	0.13	2.69 (0.56-12.97)	0.2	3.2 (0.66-15.6)	0.15
		AA vs GG	4.54 (1.05-19.64)	0.04	5.15 (1.17-22.63)	0.03	8.51 (1.78-40.54)	0.007	5.51 (1.25-24.33)	0.02	4.72 (1.09-20.48)	0.04	4.93 (1.13-21.41)	0.03
		AG vs GG	1.67 (0.69-4.02)	0.3	1.6 (0.66-3.9)	0.3	1.52 (0.6-3.82)	0.4	1.61 (0.66-3.9)	0.3	1.75 (0.73-4.24)	0.2	1.54 (0.63-3.73)	0.3
	Naples cohort	AG vs GG	1.2 (0.48-3.01)	0.7	1.2 (0.48-3.02)	0.7	1.25 (0.5-3.15)	0.6	1.26 (0.5-3.16)	0.6	1.2 (0.48-3)	0.7	1.29 (0.51-3.23)	0.6
	BCLC2 cohort + Naples cohort + Northern Italy cohort	AA vs AG	2.76 (0.92-8.27)	0.07	2.95 (0.97-9.84)	0.06	2.78 (0.9-8.56)	0.07	2.61 (0.87-7.86)	0.09	2.75 (0.92-8.25)	0.07	2.61 (0.87-7.86)	0.09
		AA vs GG	3.5 (1.27-9.67)	0.02	3.8 (1.36-10.58)	0.01	3.67 (1.31-10.3)	0.01	3.39 (1.22-9.37)	0.02	3.5 (1.27-9.66)	0.02	3.38 (1.22-9.37)	0.02
		AG vs GG	1.27 (0.73-9.67)	0.4	1.29 (0.74-2.25)	0.4	1.32 (0.75-2.32)	0.3	1.3 (0.74-2.27)	0.4	1.27 (0.73-2.22)	0.4	1.3 (0.74-2.27)	0.4
	BCLC1 cohort + Naples cohort +Northern Italy cohort	AA vs AG	1.66 (0.65-4.9)	0.4	1.63 (0.55-4.85)	0.4	1.53 (0.51-4.57)	0.5	1.54 (0.52-4.57)	0.4	1.66 (0.56-4.9)	0.4	1.54 (0.52-4.57)	0.4
		AA vs GG	1.83 (0.67-5.03)	0.2	1.73 (0.63-4.77)	0.3	1.7 (0.62-4.69)	0.3	1.8 (0.65-4.94)	0.3	1.85 (0.67-5.08)	0.2	1.79 (0.65-4.93)	0.3
		AG vs GG	1.1 (0.65-1.86)	0.7	1.06 (0.63-1.81)	0.8	1.11 (0.65-1.9)	0.7	1.17 (0.69-1.97)	0.6	1.11 (0.66-1.88)	0.7	1.16 (0.69-1.97)	0.6
	BCLC1 cohort + BCLC2 cohort + Naples cohort	AA vs AG	1.67 (0.55-5.09)	0.4	1.6 (0.53-4.87)	0.4	1.61 (0.53-4.92)	0.4	1.66 (0.55-5.06)	0.4	1.71 (0.56-5.19)	0.4	1.63 (0.54-4.95)	0.4
		AA vs GG	1.7 (0.62-4.67)	0.3	1.67 (0.61-4.59)	0.3	1.68 (0.61-4.63)	0.3	1.7 (0.62-4.67)	0.3	1.7 (0.62-4.67)	0.3	1.68 (0.61-4.62)	0.3
		AG vs GG	1.01 (0.57-1.81)	0.9	1.04 (0.58-1.86)	0.9	1.04 (0.58-1.86)	0.9	1.02 (0.57-1.82)	0.9	0.99 (0.56-1.78)	0.9	1.03 (0.58-1.84)	0.9
DAE	BCLC1 cohort	AA vs AG	2.8 (0.78-10.01)	0.1	2.45 (0.68-8.81)	0.2	2.73 (0.74-9.99)	0.13	3.09 (0.85-11.2)	0.09	2.85 (0.79-10.22)	0.11	2.86 (0.8-10.28)	0.11
		AA vs GG	1.82 (0.64-5.16)	0.3	1.61 (0.56-4.64)	0.4	1.89 (0.64-5.57)	0.2	2.12 (0.74-6.1)	0.16	1.79 (0.63-5.08)	0.3	2.03 (0.71-5.78)	0.19
		AG vs GG	0.65 (0.27-1.56)	0.3	0.66 (0.27-1.59)	0.4	0.69 (0.28-1.72)	0.4	0.69 (0.28-1.68)	0.4	0.63 (0.26-1.52)	0.3	0.71 (0.29-1.71)	0.4
	BCLC2 cohort	AA vs AG	3.83 (0.64-23.05)	0.1	3.71 (0.61-22.68)	0.2	3.91 (0.62-24.73)	0.15	4.05 (0.65-25.33)	0.14	4.49 (0.73-27.55)	0.1	3.79 (0.61-23.44)	0.15
		AA vs GG	3.22 (0.75-13.76)	0.1	3.27 (0.74-14.38)	0.1	3.74 (0.82-17.15)	0.09	3.7 (0.82-16.76)	0.09	4.04 (0.91-18)	0.07	3.18 (0.72-14.13)	0.13
		AG vs GG	0.84 (0.25-2.8)	0.8	0.88 (0.26-2.96)	0.8	0.96 (0.28-3.24)	0.9	0.92 (0.27-3.06)	0.9	0.9 (0.27-3.01)	0.9	0.84 (0.25-2.8)	0.8
	Northern Italy cohort	AA vs AG	2.85 (0.59-13.73)	0.2	3.28 (0.66-16.21)	0.1	4.71 (0.89-24.91)	0.07	3.4 (0.69-16.77)	0.13	2.83 (0.59-13.64)	0.2	3.13 (0.65-15.21)	0.16
		AA vs GG	3.68 (0.86-15.63)	0.08	4.15 (0.96-17.87)	0.06	5.97 (1.32-27.01)	0.02	4.41 (1.02-19.03)	0.046	3.97 (0.93-16.94)	0.06	3.8 (0.89-16.16)	0.07
		AG vs GG	1.29 (0.55-3.01)	0.6	1.26 (0.54-2.96)	0.6	1.27 (0.53-3.05)	0.6	1.3 (0.55-3.05)	0.6	1.4 (0.6-3.29)	0.4	1.21 (0.52-2.84)	0.7
	Naples cohort	AG vs GG	1.12 (0.45-2.77)	0.8	1.11 (0.45-2.76)	0.8	1.12 (0.45-2.79)	0.8	1.13 (0.46-2.82)	0.8	1.12 (0.45-2.77)	0.9	1.16 (0.47-2.88)	0.8
	BCCL2 cohort + Naples cohort + Northern Italy cohort	AA vs AG	2.79 (0.93-8.35)	0.07	3.04 (1-9.21)	0.049	2.72 (0.88-8.34)	0.08	2.54 (0.84-7.63)	0.1	2.74 (0.92-8.21)	0.07	2.56 (0.85-7.7)	0.09
		AA vs GG	2.96 (1.08-8.13)	0.03	3.27 (1.18-9.05)	0.02	3.07 (1.1-8.56)	0.03	2.81 (1.02-7.73)	0.045	2.94 (1.07-8.07)	0.04	2.83 (1.03-7.78)	0.04
		AG vs GG	1.06 (0.62-1.83)	0.8	1.07 (0.62-1.86)	0.8	1.13 (0.65-1.96)	0.7	1.11 (0.64-1.92)	0.7	1.07 (0.62-1.85)	0.8	1.11 (0.64-1.91)	0.7
	BCLC1 cohort + Naples cohort + Northern Italy cohort	AA vs AG	2.82 (1.13-7.07)	0.03	2.9 (1.15-7.32)	0.02	2.7 (1.06-6.84)	0.04	2.66 (1.06-6.69)	0.04	2.81 (1.12-7.05)	0.03	2.68 (1.07-6.74)	0.04
		AA vs GG	2.86 (1.24-6.58)	0.01	2.84 (1.23-6.54)	0.01	2.85 (1.24-6.57)	0.01	2.94 (1.28-6.77)	0.01	2.91 (1.27-6.7)	0.01	2.94 (1.28-6.77)	0.01
		AG vs GG	1.01 (0.61-1.68)	0.9	0.98 (0.59-1.63)	0.9	1.06 (0.63-1.77)	0.8	1.1 (0.67-1.83)	0.7	1.04 (0.63-1.71)	0.9	1.1 (0.66-1.82)	0.7
	BCLC1 cohort + BCLC2 cohort + Naples cohort	AA vs AG	2.94 (1.14-7.6)	0.03	2.85 (1.1-7.39)	0.03	3.12 (1.2-8.14)	0.02	3.21 (1.23-8.34)	0.02	3.05 (1.18-7.9)	0.02	2.9 (1.12-7.5)	0.03
		AA vs GG	2.49 (1.08-5.73)	0.03	2.48 (1.08-5.72)	0.03	2.73 (1.18-6.32)	0.02	2.75 (1.19-6.34)	0.02	2.54 (1.1-5.85)	0.03	2.51 (1.09-5.77)	0.03
		AG vs GG	0.85 (0.49-1.48)	0.6	0.87 (0.5-1.52)	0.6	0.87 (0.5-1.53)	0.7	0.86 (0.49-1.5)	0.6	0.83 (0.48-1.45)	0.5	0.87 (0.5-1.51)	0.6

eDAE: early Dermatological adverse events; DAE: Dermatological adverse events; HR: Hazard ratio; 95%CI: 95% confidence interval; BCLC: Barcelona Clinic Liver Cancer; ECOG-PS: Eastern Cooperative Oncology Group Performance Status; AHT: Arterial hypertension; DM: Diabetes mellitus.