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

Table 4 Cox regression models for eDAE and DAE by AGT1 (rs699)

Event	Centre	AGT1(rs699)	HR (95%CI)	P value	HR (95%CI) adjusted by BCLC + ECOG-PS	P value	HR (95%CI) adjusted by 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	2.31 (1.03-5.14)	0.04	2.3 (1.02-5.16)	0.04	2.34 (1.02-5.37)	0.04	2.33 (1.03-5.24)	0.04	2.45 (1.1-5.5)	0.03	2.24 (1-5.03)	0.049
		AA vs GG	1.68 (0.71-3.97)	0.2	1.69 (0.71-4)	0.2	1.64 (0.69-3.93)	0.3	1.65 (0.69-3.92)	0.3	1.75 (0.74-4.13)	0.2	1.62 (0.68-3.87)	0.3
		AG vs GG	0.73 (0.29-1.85)	0.5	0.73 (0.29-1.89)	0.5	0.7 (0.27-1.82)	0.5	0.71 (0.28-1.79)	0.5	0.71 (0.28-1.8)	0.5	0.72 (0.29-1.84)	0.5
	BCLC2 cohort	AA vs AG	0.66 (0.25-1.76)	0.4	0.63 (0.24-1.7)	0.4	0.71 (0.26-1.93)	0.5	0.72 (0.27-1.93)	0.5	0.72 (0.27-1.91)	0.5	0.68 (0.25-1.83)	0.5
		AA vs GG	1.13 (0.32-4.01)	0.9	1.08 (0.3-3.84)	0.9	1.35 (0.37-4.95)	0.7	1.36 (0.38-4.9)	0.7	1.32 (0.37-4.72)	0.7	1.13 (0.32-4)	0.9
		AG vs GG	1.71 (0.55-5.3)	0.4	1.7 (0.55-5.28)	0.4	1.89 (0.6-5.91)	0.3	1.89 (0.6-5.9)	0.3	1.85 (0.6-5.74)	0.3	1.66 (0.53-5.17)	0.4
	Northern Italy cohort	AA vs AG	0.8 (0.33-1.95)	0.6	0.75 (0.3-1.86)	0.5	1.02 (0.4-2.61)	0.9	0.96 (0.39-2.36)	0.9	0.83 (0.34-2.02)	0.7	0.91 (0.37-2.23)	0.8
		AA vs GG	0.9 (0.31-2.6)	0.8	0.71 (0.24-2.1)	0.5	0.96 (0.31-2.98)	0.9	1.22 (0.4-3.73)	0.7	0.96 (0.33-2.8)	0.9	1.12 (0.37-3.36)	0.8
		AG vs GG	1.12 (0.42-3.01)	0.8	0.95 (0.35-2.58)	0.9	0.94 (0.33-2.69)	0.9	1.27 (0.46-3.49)	0.7	1.15 (0.43-3.12)	0.8	1.23 (0.45-3.34)	0.7
	Naples cohort	AA vs AG	1.26 (0.54-2.95)	0.6	1.21 (0.51-2.86)	0.7	1.35 (0.56-3.27)	0.5	1.36 (0.57-3.25)	0.5	1.23 (0.52-2.93)	0.6	1.44 (0.61-3.39)	0.4
		AA vs GG	1.26 (0.34-4.66)	0.7	1.18 (0.31-4.43)	0.8	1.33 (0.35-5)	0.7	1.34 (0.36-4.96)	0.7	1.27 (0.34-4.68)	0.7	1.35 (0.37-5)	0.7
		AG vs GG	1 (0.28-3.51)	0.9	0.97 (0.28-3.43)	0.9	0.98 (0.28-3.49)	0.9	0.99 (0.28-3.49)	0.9	1.03 (0.29-3.65)	0.9	0.94 (0.27-3.3)	0.9
	BCLC2 cohort + Naples cohort + Northern Italy cohort	AA vs AG	0.87 (0.52-1.47)	0.6	0.85 (0.51-1.43)	0.5	0.84 (0.5-1.41)	0.5	0.85 (0.51-1.43)	0.6	0.87 (0.52-1.47)	0.6	0.85 (0.51-1.43)	0.6
		AA vs GG	1.05 (0.54-2.04)	0.9	0.95 (0.49-1.86)	0.9	0.92 (0.47-1.81)	0.8	1.01 (0.52-1.97)	0.9	1.05 (0.54-2.04)	0.9	1.01 (0.52-1.97)	0.9
		AG vs GG	1.2 (0.65-2.22)	0.6	1.12 (0.61-2.08)	0.7	1.1 (0.59-2.05)	0.8	1.18 (0.64-2.18)	0.6	1.2 (0.65-2.22)	0.6	1.18 (0.64-2.18)	0.6
	BCLC1 cohort + Naples cohort + Northern Italy cohort	AA vs AG	1.35 (0.84-2.17)	0.2	1.35 (0.84-2.18)	0.2	1.33 (0.82-2.15)	0.2	1.31 (0.81-2.11)	0.3	1.35 (0.84-2.18)	0.2	1.3 (0.81-2.1)	0.3
		AA vs GG	1.19 (0.67-2.12)	0.6	1.13 (0.6-2.01)	0.7	1.08 (0.6-1.93)	0.8	1.1 (0.61-1.97)	0.8	1.19 (0.67-2.12)	0.6	1.09 (0.61-1.96)	0.8
		AG vs GG	0.88 (0.5-1.55)	0.7	0.83 (0.47-1.48)	0.5	0.81 (0.46-1.43)	0.5	0.84 (0.48-1.48)	0.6	0.88 (0.5-1.55)	0.7	0.84 (0.48-1.48)	0.6
	BCLC1cohort + BCLC2 cohort + Naples cohort	AA vs AG	1.32 (0.81-2.15)	0.3	1.29 (0.79-2.11)	0.3	1.3 (0.79-2.12)	0.3	1.31 (0.81-2.14)	0.3	1.33 (0.82-2.17)	0.3	1.31 (0.8-2.13)	0.3
		AA vs GG	1.4 (0.75-2.6)	0.3	1.38 (0.7-2.57)	0.3	1.44 (0.77-2.69)	0.3	1.45 (0.78-2.7)	0.2	1.46 (0.79-2.72)	0.2	1.38 (0.74-2.57)	0.3
		AG vs GG	1.06 (0.58-1.94)	0.9	1.06 (0.58-1.95)	0.9	1.11 (0.6-2.03)	0.8	1.1 (0.6-2.02)	0.8	1.1 (0.6-2.01)	0.8	1.06 (0.58-1.94)	0.9
DAE	BCLC1 cohort	AA vs AG	2.7 (1.27-5.75)	0.01	2.68 (1.25-5.77)	0.01	2.52 (1.16-5.47)	0.02	2.6 (1.21-5.57)	0.01	2.82 (1.32-6.06)	0.008	2.5 (1.17-5.35)	0.02
		AA vs GG	1.26 (0.62-2.58)	0.5	1.24 (0.61-2.55)	0.6	1.11 (0.53-2.31)	0.8	1.13 (0.55-2.35)	0.8	1.3 (0.63-2.66)	0.5	1.12 (0.54-2.32)	0.8
		AG vs GG	0.47 (0.21-1.05)	0.06	0.46 (0.2-1.06)	0.07	0.44 (0.19-1.01)	0.053	0.44 (0.19-0.98)	0.045	0.46 (0.2-1.03)	0.06	0.45 (0.2-1.01)	0.052
	BCLC2 cohort	AA vs AG	0.98 (0.43-2.2)	0.9	0.94 (0.42-2.13)	0.9	0.99 (0.43-2.26)	0.9	1.01 (0.45-2.3)	0.9	1.03 (0.45-2.32)	0.9	0.95 (0.42-2.16)	0.9
		AA vs GG	1.89 (0.59-6.04)	0.3	1.78 (0.55-5.76)	0.3	2.08 (0.63-6.85)	0.2	2.18 (0.67-7.03)	0.19	2.08 (0.65-6.66)	0.2	1.88 (0.59-6.01)	0.3
		AG vs GG	1.94 (0.64-5.9)	0.2	1.89 (0.62-5.77)	0.3	2.12 (0.69-6.49)	0.19	2.15 (0.7-6.57)	0.18	2.02 (0.66-6.15)	0.2	1.98 (0.65-6.05)	0.2
	Northern Italy cohort	AA vs AG	0.89 (0.39-2.06)	0.8	0.85 (0.37-1.98)	0.7	1.01 (0.42-2.41)	0.9	1 (0.42-2.33)	0.9	0.91 (0.39-2.11)	0.8	0.95 (0.41-2.22)	0.9
		AA vs GG	0.62 (0.25-1.57)	0.3	0.54 (0.21-1.37)	0.2	0.6 (0.23-1.6)	0.3	0.74 (0.28-1.92)	0.5	0.64 (0.25-1.62)	0.4	0.7 (0.27-1.79)	0.5
		AG vs GG	0.7 (0.3-1.62)	0.3	0.63 (0.27-1.48)	0.2	0.6 (0.25-1.43)	0.2	0.74 (0.32-1.72)	0.5	0.71 (0.3-1.63)	0.4	0.73 (0.31-1.69)	0.5
	Naples cohort	AA vs AG	1.29 (0.57-2.92)	0.5	1.23 (0.54-2.81)	0.6	1.35 (0.58-3.15)	0.5	1.38 (0.6-3.17)	0.5	1.23 (0.54-2.81)	0.6	1.49 (0.66-3.4)	0.3
		AA vs GG	1.38 (0.38-5.03)	0.6	1.28 (0.35-4.73)	0.7	1.45 (0.39-5.36)	0.6	1.49 (0.41-5.41)	0.6	1.39 (0.38-5.05)	0.6	1.51 (0.41-5.51)	0.5
		AG vs GG	1.07 (0.31-3.72)	0.9	1.04 (0.3-3.62)	0.9	1.08 (0.31-3.77)	0.9	1.08 (0.31-3.79)	0.9	1.13 (0.32-3.96)	0.9	1.01 (0.29-3.52)	0.9
	BCLC2 cohort + Naples cohort + Northern Italy cohort	AA vs AG	1 (0.62-1.61)	0.9	0.98 (0.61-1.57)	0.9	0.95 (0.59-1.54)	0.9	0.97 (0.6-1.56)	0.9	1.01 (0.63-1.62)	0.9	0.96 (0.6-1.55)	0.9
		AA vs GG	1.13 (0.61-2.08)	0.7	1.04 (0.56-1.92)	0.9	0.98 (0.53-1.81)	0.9	1.05 (0.57-1.95)	0.9	1.12 (0.61-2.07)	0.7	1.05 (0.57-1.95)	0.9
		AG vs GG	1.13 (0.63-2)	0.7	1.06 (0.59-1.89)	0.8	1.02 (0.57-1.83)	0.9	1.09 (0.61-1.94)	0.8	1.12 (0.63-1.99)	0.7	1.09 (0.61-1.95)	0.8
	BCLC1 cohort + Naples cohort +Northern Italy cohort	AA vs AG	1.43 (0.91-2.24)	0.12	1.43 (0.91-2.24)	0.12	1.39 (0.88-2.19)	0.15	1.36 (0.87-2.14)	0.18	1.44 (0.92-2.26)	0.11	1.35 (0.86-2.12)	0.19
		AA vs GG	0.94 (0.57-1.56)	0.8	0.9 (0.54-1.51)	0.7	0.82 (0.49-1.38)	0.5	0.83 (0.49-1.39)	0.5	0.94 (0.57-1.57)	0.8	0.82 (0.49-1.38)	0.5
		AG vs GG	0.66 (0.4-1.09)	0.1	0.63 (0.38-1.05	0.08	0.59 (0.36-0.99)	0.04	0.61 (0.37-1.01)	0.052	0.66 (0.4-1.08)	0.1	0.61 (0.37-1.01)	0.053
	BCLC1 cohort + BCLC2 cohort + Naples cohort	AA vs AG	1.54 (0.98-2.41)	0.06	1.49 (0.95-2.34)	0.08	1.48 (0.94-2.32)	0.09	1.52 (0.97-2.37)	0.07	1.55 (0.99-2.43)	0.055	1.5 (0.96-2.35)	0.07
		AA vs GG	1.35 (0.78-2.32)	0.3	1.3 (0.75-2.25)	0.3	1.32 (0.76-2.28)	0.3	1.35 (0.78-2.33)	0.3	1.39 (0.81-2.4)	0.2	1.3 (0.76-2.24)	0.3
		AG vs GG	0.88 (0.51-1.51)	0.6	0.87 (0.51-1.5)	0.6	0.89 (0.52-1.54)	0.7	0.89 (0.52-1.54)	0.7	0.9 (0.52-1.54)	0.7	0.87 (0.5-1.49)	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.