Gallbladder cancer epidemiology, pathogenesis and molecular genetics: Recent update

Table 8 Candidate gene studies (low susceptibility genes) in gallbladder cancer

Pathway involved	Gene	Polymorphism	Population	Ref.
DNA repair pathway genes	XPC	(rs2228000) Ala499Val	China	[236]
		(rs2228001) Lys939Gln	China
	ERCC2	(rs1799793) Asp312Asn	North Indian	[232]
		(rs13181) Lys751Gln	North Indian
	MSH2	(rs2303426) IVS1+9G>C
		(rs2303425) -118T>C
	OGG1	(rs2072668) 748-15C>G
	TP53	(rs1042522) Pro72Arg	Chilean, Hungary, Japanese	[237-239]
	XRCC1	(rs1799782) Arg194Trp	North Indian Shanghai, China	[222,231]
		(rs25487) Arg399Gln
	APEX1	(rs3136820) Asp148Glu	Shanghai, China	[222]
	RAD23B	(rs1805335) IVS5-15A>G		[223]
		(rs1805329) EX7+65C>T
	FEN1	FEN1-69G>A and haplotypes	China	[240]
Hormonal pathway genes	CCKAR	(rs1800857) IVS1-5T>C	North Indian	[227]
	CCK and CCKAR	(rs2071011G>C, rs915889C/T, rs3822222C/T, rs1800855T/A	Shanghai, China,	[241]
	ESR1	(rs2234693) IVS1-397T>C	Shanghai, China, North India	[241-243]
		(rs3841686) IVS5-34->T
		(rs2228480) Ex8+229G>A
		(rs1801132) Ex4-122G>C
		(rs9340799) IVS1-351A>G
	ESR2	(rs1256049) Val328Val	Shanghai, China
	PGR	Ins/Del	North India
	AR	(CAG)n	Shanghai, China	[244]
		(rs4633) His62His	Shanghai, China	[224]
	COMT	(rs4818) Leu136Leu
	CYP1A1	(rs2606345) IVS1+606G>T
	CYP1B1	(rs10012)Arg48Gly
		(rs1065778) IVS4-76A>G	Shanghai, China	[224]
	CYP19A1	(rs700518) Val80Val
		(rs2304463) IVS7-106T>G
		(rs700519) Arg264Cys
		(rs1065779) IVS9-53G>T
		(rs4646) Ex11+410G>T
	HSD3B2	(rs1819698) Ex4-133C>T	Shanghai, China	[224]
		(rs1361530) Ex4-88C>G
	HSD17B3	(rs2066479) Gly289Arg
	HSD17B1	(rs2830) Ex1-486G>A
	SHBG	(rs6259) Ex8+6G>A
	SRD5A2	(rs523349) Ex1-17G>C
	RXR-a	(rs1536475) IVS6+70A>G	Shanghai, China	[245]
		(rs1805343) IVS1-27A>G
	RXR-b	(rs2744537) G392T
		(rs2076310) C51T
	INS	(rs689) A-6T	Shanghai, China	[245]
	PPARD	(rs2016520) Ex4+15C>T	Shanghai, China
	PPARG	(rs3856806) His477His	Shanghai, China
Inflammatory pathway genes	CR1	(rs2274567) His1208Arg	North Indian	[230]
		( rs12144461) Intron 27, HindIII
	IL1RN	86-bp VNTR	North Indian	[220]
		(rs689466) -1195G>A		[233]
	PTGS2	(rs20417) -765G>C
		(rs5275) +8473T>C	North Indian Shanghai, China	[233,246]
	IL1B	(rs16944) -1060T>C	Shanghai, China north Indian	[220,247]
	IL10	rs1800871)- 7334T>C	Shanghai	[247]
		(rs1800872) -6653A>C	Shanghai
	IL-8	(rs10805066) IL8 -13985C>G	China	[248]
	EGF	(rs4444903) +61A>G	North Indian	[221]
	TGFb1	(rs1800469)-509C>T	Shanghai, north Indian	[219,221,247]
	TNF-α	(rs1800629) -308G>A
	IL6	(rs1800795) 236C>G)
	IL8	(rs10805066) -13985C>G	China	[248]
	MMP-2	(rs2285053) -735 C>T	North Indian	[249]
		(rs9340799) -1306 C>T
	MMP-7	(rs11568818) -181 A>G
		(rs2250889) P574R
	MMP9	(rs 17576) R279Q
		(rs 17577) R668Q
	TIMP2	(rs8179090) -418 G>C
Metabolic pathway genes	MTHFR	(rs1801133) Ala222Val	Indian	[228]
	APOB	(rs17240441) 35_43del9	Indian	[217]
	NAT2	(rs1799929) NAT2*5A	Indian	[216]
		(rs1799930) NAT2*6B
		rs1799931, NAT2*7A
	GSTT1	Null polymorphism	Indian	[215]
	GSTP1	(rs1695) Ile105Val
	CYP17	(rs743572) Ex1+27T>C	Shanghai Indian (265)	[250,251]
	GSTM1	Null polymorphism	Indian, Chilean Hungary Japanese	[215,237,238]
	CYP1A1	(rs4646903) CYP1A1*2A	Indian, Chilean Hungary Japanese	[218,237,239]
		(rs1048943) Ile462Val (*2C)	China, Chilean, Hungary Japanese	[224,237-239]
	Cyp1a1 cyp1b1	CYP1A1-MspI, CYP1A1-Ile462Val, and CYP1B1-Val432Leu	India	[252]
		(rs5930) EX10+55G>A	Shanghai	[253]
	LDLR	(rs6413504) IVS17_42A>G	Shanghai
		(rs14158) EX18+88G>A
	LPL	(rs263) IVS5-540C>T
	ALOX5	(rs2029253) IVS3+100G>A
	ApoB	rs693) Thr2515Thr	Indian Chilean	[30,217]
	ABCG8	(rs11887534) Asp19His	North Indian Shanghai China	[229,254]
	CETP	(rs708272) TaqIB	Chilean Shanghai China	[30,254]
		(rs1800775) -629C>A	Shanghai China	[254]
	LRPAP1	(rs11267919)752_177_752_176 I 37	North Indian Shanghai China	[214,254]
	CYP7A1	(rs3808607) -204 A>C	North Indian	[255]
	CYP7A1	(rs3824260) -469 T>C	North Indian
	CYP17	(rs743572)A/G	North Indian	[250,251]
	ApoB	(rs676210) Pro2739Leu	Shanghai	[253]
		(rs673548) IVS23-79T>C
		rs520354) IVS6+360C > T
		(rs1367117) Thr98Ile
		(rs440446) IVS1+69C>G
	CYP2C19	(rs4244285) CYP2C19*2,	Japanese	[256]
		(rs4986893) CYP2C19*3
	ADRB3	(rs4994)A/G	North Indian	[257]
Apoptosis pathway	CASP8	(rs3834129) -652 6N ins/del	North Indian	[258]
		(rs1045485) Asp302His
		(rs3769818 A) IVS12-19 G>A
Nuclear Receptors	Lxr-alpha, Beta	LXR-α (rs7120118) and LXR-β (rs35463555 and rs2695121)	North Indian	[259]
Cancer Stem cell gene	CD44	CD44 (rs13347) C>T, CD44 (rs353639)A>C, CD44 (rs187116) G>A, CD44 (rs187115) T>C	North Indian	[260]
	NANOG, ALCAM, EpCAM, SOX-2, OCT-4, NANOG	NANOG (rs11055786)T>C,	North Indian	[261]
		ALCAM (rs1157)G>A
		EpCAM (rs1126497)T>C,
		SOX-2(rs11915160)A>C
		OCT-4 (rs3130932)T>G,
		NANOG (rs11055786)T>C
Prostate stem cell antigen	PSCA	(rs2294008) T/C and rs2978974)	India, Japan	[262,263]
miRNA	hsa-miR-146a	(rs2910164) G>C	North Indian	[264]
	hsa-mir-196a2	(rs11614913) C>T
	hsa-mir-499	(rs3746444)T>C
	miR-27,miR-570,miR-181	miR-27a (rs895819)A>G,	North Indian population	[265]
		miR-570(rs4143815)G>C,
		miR-181a(rs12537)C>T
GWAS-associated genes	DCC	(rs7504990)C>T	Japan	[234]
		( rs2229080) C>G	North Indian	[235]
		(rs4078288) A>G
		(rs7504990) C>T
		(rs714) A>G
Wnt signaling pathway	SFRP4, DKK2, DKK3, APC, AXIN-2, Β-CATENIN, GLI-1	SFRP4 (rs1802073) G>T,	North Indian	[266]
		DKK2 (rs17037102) C>T
		DKK3 (rs3206824) C>T,
		APC (rs4595552)A/T
		APC ( rs11954856) G>T,
		AXIN-2 (rs4791171)C>T
		β-CATENIN (rs4135385) A>G,
		GLI-1(rs222826) C>G
Other genes	KRAS	codon 25 Gln25His	Eastern India	[267]
	ACE I/D	(rs4646994) 289 bp del	North Indian	[268]
	DNMT3B	(rs1569686) -579 G>T	North Indian	[269]
	TLR2	-196-174del	North Indian	[270]
	TLR4	(rs4986791) Thr399Ile	North Indian
	Adrenergic receptors (ADRA)	ADRA2A C-1291G, ADRβ3 T190C or Trp64Arg, and ADRβ1 C1165G or Arg389Gly	North Indian	[271]
	Death Receptors and their ligands (DR4)	DR4 (rs20575, rs20576 and rs6557634), FAS (rs2234767) FASL (rs763110)	North Indian
	PlCE1	(rs2274223) A>G and. (rs7922612) T>C	North Indian	[272]
	Vitamin D receptor (VDR)	FokI C>T	China	[273]