Early detection of gallbladder cancer: Current status and future perspectives

Table 9 Genetic biomarkers that mutated in early carcinogenesis and can be used for early diagnosis

Genes	Mutation	Method of identification	Role in early diagnosis	Ref.
TLR2, TLR4	Polymorphism	PCR-RFLP	TLR4 Ex4 + 936C>T polymorphism (g.14143C>T; rs4986791) significantly associated with the overall higher risk of GBC in north Indian population	[131]
CYP1A1 (rs2606345)	Polymorphism	TaqMan assay	Associated with increased risk of biliary tract cancer in Chinese populations	[136]
TP 53	Point mutation/loss of heterozygosity	PCR/RFLP	Found in both early and advanced GBC, associated with pre malignant conditions in Indian, Japanese Chile and bolivian population	[137,173-175]
KRAS	Mutation (codon 12/13)	PCR-RFLP	Seen in early lesions; potential marker for pre-malignant transformation	[176]
CDKN2A (p16)	Promoter methylation or loss of homozygosity	PCR-RFLP	Acquisition of hypermethylation contribute to tumor formation and progression within the chronically inflamed gallbladder at early stage of carcinogenesis	[177,178]
ABCG8	Polymorphism	GWAS/PCR-RFLP	Increased risk of GBC in patients with gall stone disease	[179]
ERCC2, MSH2	-	PCR-RFLP	Associated with early steps of carcinogenesis	-

GBC: Gall bladder cancer; PCR-RFLP: Polymerase chain reaction - restriction fragment length polymorphism; GWAS: Genome-wide association study.