MicroRNA binding site polymorphisms as biomarkers in cancer management and research

Figures & data

Table 1 List of micro-RNA binding sites evaluated in epidemiologic studies

Single nucleotide polymorphism ID	Gene	Race	Information	Predicted binding site for	Disease	Cases	Controls	Endpoint	Best result	P-value	Assay	Ref
rs16917496	SET8	AS	T>C (0.32)	miR-502	NSCLC	576		OS (months) OS (RR; 95%CI)	41.0 vs 58.0 0.44 (0.26–0.74)	0.031 0.006	Gene reporter in vitro assay and IHC on tissues	^Citation27
rs16917496	SET8	AS	T>C (0.32)	miR-502	SCLC	44		OS (RR)	0.45 (0.22–0.94)	0.035		^Citation28
rs16917496	SET8	AS	T>C (0.32)	miR-502	BC	1,100		AO (years)	54.6 vs 47.7			^Citation76
rs16917496	SET8	AS	T>C (0.32)	miR-502	HCC	142	142	Risk (OR; 95%CI) OS (RR)	NS 0.17 (0.05–0.58)	NS 0.004	IHC in HCC tissues	^Citation107
rs1564483	BCL2	AS	G>A (0.29)	miR-181b miR-204 miR-200bc/429	NSCLC	1,017 1,017	1,017	Risk (OR) MST (months)	0.73 (0.54–0.98) 11.7 vs 15.2	0.007 0.036		^Citation29
rs2240688	CD133	AS	A>C (0.27)	miR-135a/b	LC	773 503 559 331	778 623	Risk (OR) Risk (OR) MST (months) MST (months)	0.80 (0.65–0.98) 0.80 (0.63–1.00) 10 vs 12 14 vs 18	0.027 0.05 0.02 0.081	Gene reporter in vitro assay + mRNA and IHC on tissue	^Citation35
rs3660	KRT81	CAU	C>G (0.41)	miR-20a/b miR-106a/b miR-17 miR-93 miR-519d	NSCLC SCC	175 89		TTR (months) TTR (months)	20.3 vs 86.8 23.9 vs 100.2	0.003 0.002	In silico prediction + IHC on tissues	^Citation17
rs2239680	B1RC5	AS	T>C (0.23)	miR-335	LC	600 1,000	600 1,000	Risk (OR) Risk (OR)	3.43 (2.04–5.77) 1.63 (1.17–2.26)	<0.01 <0.01	Gene reporter in vitro assay + mRNA and IHC on tissues	^Citation44
rs61764370	KRAS	HISP CAU	T>G (0.03) T>G (0.08)	let-7	NSCLC	325 2,205	325 1,497	Risk (OR) Risk (OR)	2.3 (1.1–4.6) 1.36 (1.07–1.73)	0.02 0.01	Gene reporter in vitro assay	^Citation45
rs61764370	KRAS	CAU	T>G (0.08)	let-7	NSCLC	218		OS		NS		^Citation46
rs61764370	KRAS	CAU	T>G (0.08)	let-7	CRC	409 (stage I, II) 182 (stage III) 69 (stage IV)		Risk (RR) OS (HR) NS NS	0.68 (0.49–0.94) 0.46 (0.18–1.04)	0.038		^Citation51
rs61764370	KRAS	CAU	T>G (0.08)	let-7	CRC	100		Responder (%)	31.9 vs 0.0	0.004		^Citation55
rs61764370	KRAS	CAU	T>G (0.08)	let-7	BC	268 (BRCA1 carriers) 89 (BRCA2 carriers) 685 noncarriers	797	Risk (OR) Risk (OR) Risk (OR)	1.47 (1.05–2.06) NS NS	0.025		^Citation94
rs61764370	KRAS	CAU	T>G (0.08)	let-7	OC	100 308	101 322	Risk (OR) Risk (OR)	2.38 (1.16–5.09) 2.01 (1.36–2.99)	0.02 0.0005		^Citation104
rs61764370	KRAS	CAU	T>G (0.08)	let-7	HNC	513	597	Risk (OR) OS (HR)	NS 2.5 (1.3–4.9)	<0.01		^Citation126
rs2735383	NBS1	AS	G>C (0.39)	miR-629	LC	1,056 503	1,056 623	Risk (OR) Risk (OR)	1.47 (1.15–1.86) 1.55 (1.12–2.15)	0.008 0.026	Gene reporter in vitro assay + WB + chromosome aberration challenge assay	^Citation47
rs465646	REV3L	AS	T>C (0.17)	miR-25 miR-32	LC	500 572	517 547	Risk Risk	0.69 (0.53–0.90) 0.72 (0.55–0.94)	0.007 0.016	Cell focus formation assay and gene reporter in vitro assay	^Citation48
rs3134615	MYCL1	AS	G>T (0.02)	miR-1827	SCLC	666	758	Risk (OR)	2.08 (1.39–3.21)	0.0004	Gene reporter in vitro assay	^Citation50
rs1534862	NE1L2	CAU	T>C (0.05)		CRC	718 229		OS (HR)	1.66 (1.18–2.34)	0.003	In silico prediction	^Citation57
rs2233921	SMUG1	CAU	G>T (0.46)	miR-770-5p miR-665 miR-455-3p	CRC	718 229		OS (HR)	0.54 (0.36–0.81)	0.003	Gene reporter in vitro assay	^Citation57
rs10082466	MBL2	AA	A>G (0.39)	miR-27a	CRC	103	127	Risk (OR)	3.17 (1.57–6.40)	0.001	Gene reporter in vitro assay	^Citation1
rs696	NFkBIA	AS	A>G (0.37)	miR-449 miR-34	CRC	1,001	1,005	Risk (OR)	1.38 (1.14–1.66)	0.0008	Gene reporter in vitro assay	^Citation63
rs70980S	KIAA0182	CAU	G>A (0.26)	miR-324-3p	CRC	717	739	Risk (OR)	1.57 (1.06–2.7)	0.027	Gene reporter in vitro assay	^Citation64
rs354476	NUP210	CAU	T>C (0.47)	miR-125a miR-125b	CRC	717	739	Risk (OR)	1.36 (1.02–1.82)	0.0045	Gene reporter in vitro assay	^Citation64
rs17281995	CD86	CAU	G>C (0.12)	miR-337 miR-582 miR-200a miR-184 miR-212	CRC	697	624	Risk (OR)	2.74 (1.24–6.04)	0.013	In silico prediction	^Citation10
rs1051690	INSR	CAU	G>A (0.14)	miR-618 miR-612	CRC	697	624	Risk (OR)	1.94 (1.03–3.66)	0.03	In silico prediction	^Citation10
rs7356	RPA2	CAU	A>G (0.38)	miR-3149 miR-1183	CRC	1,098	1,469	Risk (OR)	1.33 (1.01–1.75)	0.04	In silico prediction	^Citation71
rs4596	GTF2H1	CAU	G>C (0.37)	miR-518a-5p miR-527 miR-1205	CRC	1,098	1,469	Risk (OR)	0.79 (0.64–0.99)	0.03	In silico prediction	^Citation71
rs115160714	TOPBP1	CAU	C>T (0.005)	miR-3138 miR-4302 miR-1207-5p	BC	534	556	Risk (OR) Grading (G3)	3.54 (1.56–8.39) 6.83 (2.75–16.86)	0.002 0.0001	In silico prediction and mRNA expression + protein on tissue	^Citation78
rs1044129	RYR3	AS	A>G (0.44)	miR-367	BC	1,532 1,125	1,600	Risk (OR) PFS (HR)	1.26 (1.03–1.54) 2.20 (1.03–4.70)	0.028 0.042	Gene reporter in vitro assay and IHC on tissues	^Citation84
rs743554	ITGB4	CAU	G>A (0.14)	miR-34a	BC	749 244	1,493	Risk (OR) Grading (G3) HR OS (HR)	7.65 (1.44–0.7) 2.26 (1.17–4.37) 2.11 (1.21–3.68)	0.017 0.015 0.0085	In silico prediction	^Citation85
rs4245739	MDM4	AS	A>C (0.05)	miR-191	BC	1,100 1,100	1,400 1,400	Risk (OR) Risk (OR)	0.55 (0.40–0.76) 0.41 (0.25–0.67)	0.00023 0.00031	Gene reporter in vitro assay	^Citation87
rs4245739	MDM4	AS	A>C (0.05)	miR-191	OC	154 113	154	Risk (OR) PFS (months)	52 vs 82	NS 0.042	Gene reporter in vitro assay + mRNA expression and IHC on tissues	^Citation102
rs4245739	MDM4	AS	A>C (0.05)	miR-191	ESCC	540 588	550 600	Risk (OR) Risk (OR)	0.54 (0.35–0.82) 0.68 (0.44–0.99)	0.004 0.049	mRNA expression on tissue	^Citation137
rs796355l	RAD52	AS	T>G (0.19)	let-7 b	BC	878 914	900 967	Risk (OR) Risk (OR)	0.85(0.71–1.07) 0.81 (0.68–0.97)	0.12 0.02	Gene reporter in vitro assay	^Citation88
rs799917	BRCA1	CAU	C>T (0.34)	miR-638	BC	166 (sporadic) 169 (familial)	186 186	Risk (OR) Risk (OR)	2.81 (1.40–5.61) 1.26(0.59–2.71)	0.003 NS	Gene reporter in vitro assay	^Citation90
rs334348	TGFBR1	CAU	A>G (0.23)	miR-628-5p	BC	166 (sporadic) 169 (familial)	186 186	Risk (OR) Risk (OR)	2.67 (1.19–6.03) 1.26 (0.59–2.71)	0.002 0.55	Gene reporter in vitro assay	^Citation90
rs1042538	IQGAP1	AS	A>T (0.43)	miR-124	BC	1,541	1,598	Risk (OR)	0.78 (0.61–0.99)	0.049	mRNA and protein expression in frozen tissues	^Citation91
rs2747648	ESR1	CAU	T>C (0.042)	miR-453	BC	1,223 721 (<50 years old) 438 (high risk fam)	1,495 713 659	Risk (OR) Risk (OR) Risk (OR)	0.73 (0.54–0.97) 0.60 (0.41–0.89) 0.53 (0.35–0.79)	0.029 0.010 0.002	In silico prediction	^Citation95
rs10889677	IL23R	AS	A>C (0.33)	Let-7e Let-7f	BC	491 491	502	Risk (OR) AO (years)	1.40 (1.09–1.79) 46.0 vs 50.6	0.0084 0.0114	In silico prediction	^Citation99
rs17147016	UGT2A3	CAU	T>A (0.13)	miR-224	OC	417	417	Risk (OR)	1.47 (1.08–2.01)	0.015	In silico prediction	^Citation103
rs7499	COL18A1	CAU	G>A (047)	miR-594	OC	417	417	Risk (OR)	1.47 (1.07–2.02)	0.017	In silico prediction	^Citation103
rs3917328	IL1R1	CAU	C>T (0.04)	miR-335	OC	417	417	Risk (OR)	1.65 (1.03–2.64)	0.037	In silico prediction	^Citation103
rs10771184	KRAS	CAU	T>A (0.45)	miR-544	OC	417 417	417	Risk (OR) OS (HR)	1.26 (1.01–1.57) 0.56 (0.38–0.84)	0.005	In silico prediction	^Citation103
rs1425486	PDGFC	CAU	G>A (0.34)	miR-425	OC	417		OS (HR)	2.69 (1.67–4.33)	4.2×10^−5	In silico prediction and gene reporter in vitro assay	^Citation103
rs1047920	SNAI1	CAU	C>T (0.08)	miR-24	OC	417		OS (HR)	1.96 (1.30–2.97)	0.0038	In silico prediction	^Citation103
rs7869402	TLR4	CAU		miR-539	OC	417		OS (HR)	2.16 (1.31–3.57)	0.002	In silico prediction	^Citation103
rs17875871	IFNAR1	AS	Del (0.12)	miR-1231	HCC	420	420	Risk (OR)	1.84 (1.18–2.84)	0.006	In silico prediction	^Citation108
rs3783553	IL1A	AS	In (0.29)	miR-122 miR-378	HCC	403 1,074	434 1,239	Risk (OR) Risk (OR)	0.30 (0.17–0.54) 0.75 (0.57–0.98)	0.0001 0.0328	Gene reporter in vitro assay	^Citation112
rs5622877l	SGSM3	AS	In ND	miR-151-5p	HCC	502	513	Risk (OR)	0.55 (042–0.73)	1.03×10^−5	In silico prediction and mRNA expression on tissue	^Citation113
rs6147150	EERB4	AS	Del ND	let-7c	HCC	270	270	Risk (OR)	1.59 (1.22–2.07)	0.003	In silico prediction	^Citation114
rs8679	PARP1	CAU	T>C (0.21)	miR-145 miR-105 miR-630 miR-302a	BlC	752	704	Risk (OR)	1.29 (1.02–1.62)	0.05	In silico prediction	^Citation116
rs7180135	RAD51	CAU	A>G (0.44)	miR-197	BlC	202		OS (HR)	0.52 (0.31–0.87)	0.01	In silico prediction	^Citation116
rs1417608	HSD3B2	CAU	A>G (0.07)	miR-423-5p miR-1914 miR-3658	BlC	563 497	863 957	Risk (OR) Risk (OR)	1.94 (1.36–2.75) 3.66 (1.06–12.63)	0.001 0.04	In silico prediction	^Citation117
rs9299	HOXB5	CAU	A>G (0.37)	miR-7	BlC	391	391	Risk (OR) Grading (T2–T4)	2.05 (1.06–3.94) 2.25 (1.33–3.79)	0.031 0.003	Gene reporter in vitro assay	^Citation121
rs88422S	EGFR	AS	A>G (0.39)	miR-214	BlC	908	1,239	Risk (OR)	1.40 (1.09–1.80)	0.008	Gene reporter in vitro assay	^Citation122
rs3747238 G allele	SMC1B	CAU	T>C (0.46)	miR-609 miR-124a	HNC	150 with recurrence 300 w/t recurrence		ROR (HR) TTR (months)	1.74 (1.19–2.54) >93 vs 75.8	0.004 0.019	In silico prediction	^Citation125
rs8126	TNFA1P2	CAU	T>C (0.37)	miR-184	HNC	1,077	1,073	Risk (OR)	1.48 (1.06–2.05)	0.02	Gene reporter in vitro assay + mRNA expression on tissue	^Citation127
rs8126	TNFA1P2	CAU	T>C (0.37)	miR-184	GC	301	313	Risk (OR)	2.00 (1.09–3.64)	0.024		^Citation130
rs712	KRAS	AS	T>G (0.18)	let-7	GC	118	674	Risk (OR)	3.05 (1.53–6.08)	0.00153		^Citation131
rs12537	MTMR3	AS	C>T(0.23)	miR-181a	GC	500	502	Risk (OR) OS (HR)	1.72 (1.36–2.16) 1.38 (1.03–1.83)	3.99×10^−5 0.029	Gene reporter in vitro assay	^Citation132
rs6573	RAP1A	AS	C>A (0.11)	miR196a	ESCC	536	608	Risk (OR)	0.43 (0.21–0.91)	0.02	Gene reporter in vitro assay	^Citation135
rs1131445	IL16	AA	T>C (0.25)	miR-135a/b	PC	256		OS (HR)	3.0 (1.23–7.12)	0.014		^Citation137
rs11902171	ITGAv	AS	G>C (0.08)		PC	347	367	Risk (OR)	0.57 (0.35–0.93)	0.024		^Citation141
rs1434536	BMPR1B	AS	C>T (0.34)	miR-125b	PC	247	278	Risk (OR)	1.90 (1.15–3.15)	0.015	Gene reporter in vitro assay	^Citation143

Notes: The results are reported for the less common (underlined) allele, using the most common allele as reference. The table resumes the best associations reported in the cited study.

Abbreviations: ID, identification number; Ref, reference; AS, Asian; T, timeline; miR, microRNA; NSCLC, non-small-cell lung cancer; OS, overall survival; RR, relative risk; IHC, immunohistochemistry; SCLC, small cell lung cancer; BC, breast cancer; AO, age of onset; HCC, hepatocellular carcinoma; OR: odds ratio; NS, statistically nonsignificant; LC, lung cancer; MST, median survival time; mRNA, messenger RNA; CAU, Caucasian; SCC, squamous cell carcinoma; TTR, time to recurrence; HIS, Hispanic; HR, hazard ratio; CRC, colorectal cancer; OC, ovarian cancer; HNC, head and neck cancer; WB, western blot; AA, African American; PFS, progression-free survival; ND, not detected; BlC, bladder cancer; ROR, risk of recurrence; GC, gastric cancer; ESCC, esophageal cancer; PC, prostate cancer ; vs, versus; fam, familiar; In, insertion; Del, deletion; w/t, without.

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