Advances in Urology

Review Article

Predictive Biomarkers of Bacillus Calmette-Guérin Immunotherapy Response in Bladder Cancer: Where Are We Now?

Table 3

Genetic polymorphisms associated to BCG outcome. The markers are ordered from the most studied to the less, and, within each marker, the studies are ordered by quality score.


Marker	Author	Quality	n	Treatment scheme	Impact	RFS (P/HR (95% CI))

NRAMP
D543N GG	Chiong et al., [73]	6/8	99	mBCG	−	0.033/4.6 (1.4–15.2)
D543N GA	Decobert et al., [74]	6/8	67	iBCG + mBCG	−	0.0271/5.74 (2.4–13.8)
(GT)n allele 3	Chiong et al., [73]	6/8	99	mBCG	−	NS/24.8 (3.08–199.9)
	Decobert et al., [74]	6/8	67	iBCG + mBCG	None	NS/NS
469 + 14 G/C	Decobert et al., [74]	6/8	67	iBCG + mBCG	None	NS/NS
274 C/T	Decobert et al., [74]	6/8	67	iBCG + mBCG	None	NS/NS
1465 − 85 G/A	Decobert et al., [74]	6/8	67	iBCG + mBCG	None	NS/NS

XPA 5^′UTR A/G	Gu et al., [75]	6/8	112	iBCG + mBCG	−	0.078

XPC
Lys 939 Gln	Gangwar et al., [76]	7/8	77	iBCG	−	0.044/3.98 (1.02–10.7)^*
	Gu et al., [75]	6/8	112	iBCG + mBCG	None	NS
PAT ins/del	Gangwar et al., [76]	7/8	77	iBCG	None	NS^*
	Gu et al., [75]	6/8	112	iBCG + mBCG	None	NS
Ala 499 Val	Gu et al., [75]	6/8	112	iBCG + mBCG	None	NS

XPD
Asp312Asn	Gu et al., [75]	6/8	112	iBCG + mBCG	None	NS
Lys751Gln	Gu et al., [75]	6/8	112	iBCG + mBCG	None	NS

XPG Asp1104His	Gu et al., [75]	6/8	112	iBCG + mBCG	None	NS

IL8
−251 T/A	Ahirwar et al., [81]	7/8	71	iBCG	+	<0.001/0.12 (0.04–0.38)
	Leibovici, [86]	6/8	123	iBCG/mBCG	None	NS/NS
+678 C/T	Ahirwar et al., [81]	7/8	71	iBCG	None	NS

TNFA
−1031 T/C	Ahirwar et al., [85]	7/8	73	iBCG	+	0.024/0.38 (0.14–0.98)
−857 C/T	Ahirwar et al., [85]	7/8	73	iBCG	None	NS
−863 C/A	Ahirwar et al., [85]	7/8	73	iBCG	None	NS
−308 G/A	Ahirwar et al., [84]	6/8	69	iBCG	None	NS
	Leibovici, [86]	6/8	123	iBCG/mBCG	None	NS/NS

IL6 −174 G/C	Ahirwar et al., [84]	6/8	69	iBCG	+	0.021/0.298 (0.09–091)
	Leibovici, [86]	6/8	123	iBCG/mBCG	−	NS/4.6 (1.24–17)

hGPX Pro198Leu C/T	Chiong et al., 2010 [73]	6/8	99	mBCG	None	NS

MMP1
−519 A/G	Srivastava, [90]	6/8		iBCG	None	NS
−1607 1G/2G	Srivastava, [90]	6/8		iBCG	+	0,030

MMP2
−735 C/T	Srivastava, [91]	7/8	78	iBCG	None	NS
−1306 C/T	Srivastava, [91]	7/8	78	iBCG	−	0.039/2.06 (1.01–4.18)

MMP3
−1171 5A/6A	Srivastava, [92]	6/8	78	iBCG	−	0.025/2.01 (0.98–4.12)
Rs6796720 G/A	Srivastava, [92]	6/8	78	iBCG	None	NS
Rs 520540 A/G	Srivastava, [92]	6/8	78	iBCG	None	NS

MMP7 −181 A/G	Srivastava, [90]	6/8		iBCG	None	NS

MMP8 +799 C/T	Srivastava, [91]	7/8	78	iBCG	None	NS

MMP9
Q279R A/G	Srivastava, [92]	6/8	78	iBCG	None	NS
P574R G/C	Srivastava, [92]	6/8	78	iBCG	None	NS
R668Q G/A	Srivastava, [92]	6/8	78	iBCG	None	NS
ERCC1 3^′UTR G/T	Gu et al., [75]	6/8	112	iBCG/mBCG	None	NS

ERCC2
Asp312Asn G/A	Gangwar et al., [77]	6/8	74	iBCG	−	0.005/3.07 (1.22–7.68)
Lys751Gln A/C	Gangwar et al., [77]	6/8	74	iBCG	None	NS

ERCC6
Met1097Val A/G	Gu et al., [75]	6/8	112	iBCG/mBCG	−	0.022
Arg1230Pro G/C	Gu et al., [75]	6/8	112	iBCG/mBCG	None	NS

APEX1 Asp148Glu T/G	Gangwar et al., [77]	6/8	74	iBCG	None	NS

COX2
−1290 A/G	Gangwar et al., [83]	6/8	79	iBCG	None	NS
−1195 G/A	Gangwar et al., [83]	6/8	79	iBCG	None	NS
−765 G/C	Gangwar et al., [83]	6/8	79	iBCG	−	2.43 (0.34–1.85)
+8473 T/C	Gangwar et al., [83]	6/8	79	iBCG	None	NS

IFNA LOH	Cai, [82]	7/8	77	mBCG	−	<0.0001/4.09 (2.59–6.28)^*

IFNG +874 T/A	Ahirwar et al., [80]	7/8	73	iBCG	−	2.24 (1.06–5.80)

NFkB ATTG Ins/Del	Ahirwar et al., [81]	7/8	71	iBCG	−	0.031/2.53 (1.00–6.36)

CASP9
−1263 A/G	Gangwar et al., [88]	7/8	79	iBCG	+	0.024/0.27 (0.15–0.62)
−293 Ins/Del	Gangwar et al., [88]	7/8	79	iBCG	None	NS

CASP8 −6N Ins/Del	Gangwar et al., [88]	7/8	79	iBCG	None	NS

IL4 VNTR	Ahirwar et al., [84]	6/8	69	iBCG	None	NS

IL1B −511 C/T	Ahirwar et al., [80]	7/8	73	iBCG	None	NS

IL1RN VNTR	Ahirwar et al., [80]	7/8	73	iBCG	None	NS

TGFB1 +28 C/T	Ahirwar et al., [80]	7/8	73	iBCG	+	0.37 (0.14–0.98)

MDM2 +309 G/T	Gangwar et al., [89]	6/8	79	iBCG	+	0.25 (0.08–0.80)

CCDN1 +870G/A	Gangwar et al., [89]	6/8	79	iBCG	None	NS

FAS −670A/G	Gangwar et al., [89]	6/8	79	iBCG	None	NS

XRCC1
Arg194Trp C/T	Mittal et al., [78]	5/8	61	iBCG	None	NS^*
Arg280His G/A	Mittal et al., [78]	5/8	61	iBCG	None	NS^*
Arg399Gln G/A	Mittal et al., [78]	5/8	61	iBCG	−	0.004/5.05 (1.34–19.01)^*

XRCC3
+18067 C/T	Mittal et al., [79]	7/8	73	iBCG	None	NS
+17893 A/G	Mittal et al., [79]	7/8	73	iBCG	None	NS

XRCC4
+1394 G/T	Mittal et al., [79]	7/8	73	iBCG	None	NS
Intron 3 (rs2836007)	Mittal et al., [79]	7/8	73	iBCG	None	NS
Intron 7 (rs2836317)	Mittal et al., [79]	7/8	73	iBCG	None	NS
Intron 7 (rs1805377)	Mittal et al., [79]	7/8	73	iBCG	None	NS

PPARG Pro12Ala	Leibovici, [86]	6/8	123	iBCG/mBCG	None	NS/NS

GLI3
rs6463089 G/A	Chen et al., [93]	7/8	204	iBCG + mBCG	−	2.40 (1.50–3.84)^*
rs3801192 G/A	Chen et al., [93]	7/8	204	iBCG + mBCG	−	2.54 (1.47–4.39)^*

iBCG: induction BCG scheme only.
mBCG: maintenance BCG scheme.
−: negative impact, marker associated with a poor BCG response.
+: positive impact, marker associated to a better BCG response.
RFS: recurrence-free survival; P value for log-rank test/HR: hazard ratio from Cox regression; (95% Cl): 95% confidence interval.
NS: no statistical significance.
^*all analysed variables (indepent prognostic factor).
adjusted for age, gender, ethnicity, tumour stage and grade, smoking history, and BCG vaccination status.
adjusted for Cis background, multifocality, and mBCG treatment.
adjusted for age, gender, and smoking history.
adjusted for age, gender, smoking history, and grade.
adjusted for age and gender.