Hereditary breast cancer: ever more pieces to the polygenic puzzle

Bogdanova, Natalia; Helbig, Sonja; Dörk, Thilo

doi:10.1186/1897-4287-11-12

Hereditary Cancer in Clinical Practice

Table 2 Genomic loci harbouring low-penetrance breast cancer susceptibility alleles

From: Hereditary breast cancer: ever more pieces to the polygenic puzzle

Locus	SNP	Reported gene	Nearby genes (selected)	Association with ER status	Reference
1p11	rs2580520, rs11249433	EMBP1	HIST3, HIST2H2BA	ER + ve ~ ER-ve	[99, 101, 119, 120]
1p13	rs11552449	DCLRE1B	PTPN22, HIPK1, BCL2L15	ER + ve > ER-ve	[72]
1p36	rs616488	PEX14	KIF1B, UBE4B, RBP7	ER-ve > ER + ve	[37]
1q32	rs4245739	MDM4	PIK3C2B	ER-ve	[115]
1q32	rs6678914	LGR6	UBE2T, PTPN7	ER-ve	[115]
2p24	rs12710696	intergenic	OSR1	ER-ve	[115]
2q14	rs4849887	intergenic	INHBB, RALB, GLI2	ER + ve ~ ER-ve	[72]
2q31	rs2016394	intergenic	DLX1, DLX2, ITGA6, PDK1	ER + ve	[72]
2q31	rs1550623	intergenic	CDCA7, MLK7-AS1, ZAK	ER + ve ~ ER-ve	[72]
2q33	rs1045485, rs10931936, rs3834129- rs6723097-rs3817578	CASP8	CASP10, ORC2, CDK15	ER + ve ~ ER-ve	[101, 121, 122]
2q34	rs13393577	ERBB4	MIR4776	ER + ve ~ ER-ve	[110]
2q35	rs13387042, rs16857609	DIRC3	PINC, TNS1, IGFBP1, IGFBP5	ER + ve > ER-ve	[72, 97, 103, 123, 124]
3p24	rs4973768	SLC4A7	NEK10	ER + ve > ER-ve	[98, 101, 103]
3p24	rs12493607	TGFBR2	GADL1	ER + ve	[72]
3p26	rs10510333	intergenic	GRM7	ER + ve ~ ER-ve	[113]
3p26	rs6762644	ITPR1	SUMF1, BHLHE40	ER + ve	[72]
3q25	rs6788895	SIAH2	MED12L, SELT, EIF2A	ER + ve	[112]
3q26	rs3806685	intergenic	PIK3CA, ZNF639	ER + ve ~ ER-ve	[110]
4q24	rs9790517	TET2	PPA2	ER + ve	[72]
4q34	rs6828523	ADAM29	GLRA3	ER + ve	[72]
5q11	rs889312, rs16886165	intergenic	MAP3K1, MIER3	ER + ve > ER-ve	[95, 99, 101]
5q11	rs1353747, rs10472076	PDE4D	RAB3C, PDK2	ER + ve ~ ER-ve	[72]
5p12	rs4415084, rs10941679, rs7716600, rs9790879, rs4866929	intergenic	HCN1, MRPS30,FGF10	ER + ve > ER-ve	[96, 97, 101, 103, 124]
5p15	rs1092913	intergenic	MARCH6, DAP	ER + ve > ER-ve	[105, 110]
5p15	rs2736108, rs10069690, rs2242652	TERT	CLPTM1L	variant specific	[104, 114]
5q33	rs1432679	EBF1	RNF145, UBLCP1	ER + ve ~ ER-ve	[72]
6p23	rs204247	intergenic	RANBP9, SIRT5, CCDC90A	ER + ve	[72]
6p24	rs9348512	intergenic	GCNT2, PAK1IP1, TFAP2A	BRCA2 specific	[118]
6p25	rs11242675	intergenic	FOXQ1, FOXF2, FOXC1	ER + ve ~ ER-ve	[72]
6q14	rs17529111, rs17530068	intergenic	FAM46A, IBTK, SSBP2	ER + ve ~ ER-ve	[72, 109]
6q25	rs9498283	TAB2	SUMO4, LATS1	ER + ve ~ ER-ve	[110]
6q25	rs3757318, rs12662670, rs6929137, rs3734804, rs3734805, rs2046210	intergenic	ESR1	variant specific	[100, 101, 103, 106, 125–127]
7q32	rs2048672	FLJ43663	MIR29A, KLF14	not mentioned	[106]
7q35	rs720475	ARHGEF5	NOBOX	ER + ve	[72]
8p12	rs9693444	intergenic	DUSP4, KIF13B	ER + ve ~ ER-ve	[72]
8q21	rs6472903, rs2943559	HNF4G	CRISPLD1, ZFHX4	ER + ve > ER-ve	[72]
8q24	rs672888, rs1562430, rs13281615, rs11780156	intergenic	PVT1, MIR1204-08, MYC	ER + ve ~ ER-ve	[72, 95, 101, 103]
9p21	rs1011970	CDKN2B	CDKN2A, CDKN2B-AS1	ER + ve > ER-ve	[101]
9q31	rs865686, rs10759243	intergenic	RAD23B, KLF4	ER + ve > ER-ve	[72, 103]
10p12	rs7072776, rs11814448	intergenic	DNAJC1, MLLT10	ER + ve ≠ ER-ve	[72]
10p15	rs2380205	intergenic	ANKRD16, FBXO18, GDI2	ER + ve ~ ER-ve	[101]
10q21	rs10822013, rs10995190	ZNF365	EGR2, NRBF2	ER + ve > ER-ve	[101, 106]
10q22	rs704010, rs12355688	ZMIZ1	PPIF, ZCCHC24, EIF5AL1	ER + ve ~ ER-ve	[101, 113]
10q25	rs7904519	TCF7L2	ZDHHC6, CASP7, DCLRE1A	ER + ve ~ ER-ve	[72]
10q26	rs2981582, rs11199914, rs2981579, rs1219648, rs10510102	FGFR2	WDR11, TACC2	ER + ve	[72, 95, 96, 99, 101, 103, 124]
11p15	rs3817198, rs909116	LSP1-TNNT3	CTSD, DUSP8, IGF2	ER + ve ~ ER-ve	[95, 101, 128]
11q13	rs3903072	intergenic	RELA, MAP3K11, MUS81	ER + ve	[72]
11q13	rs614367, rs661204, rs78540526, rs554219, rs657686, rs75915166	intergenic	CCND1, FGF19, FGF4, FGF3	ER + ve > ER-ve	[101, 116]
11q24	rs11820646	intergenic	BARX2, NFRKB, PRDM10	ER + ve ~ ER-ve	[72]
12p11	rs10771399	PTHLH	CCDC81	ER + ve ~ ER-ve	[108]
12p13	rs12422552	intergenic	ATF7IP, GRIN2B, PLBD1	ER + ve ~ ER-ve	[72]
12q22	rs17356907	intergenic	NTN4, USP44, METAP2, NR2C1 VEZT, FGD6, CCDC38	ER + ve ~ ER-ve	[72]
12q24	rs1292011	intergenic	TBX3	ER + ve > ER-ve	[108]
14q13	rs2236007	PAX9	NKX2-8	ER + ve > ER-ve	[72]
14q24	rs999737, rs2588809, rs1314913, rs10483813, rs8009944,	RAD51B	ZFP36, ACTN1, DCAF5	ER + ve	[72, 99, 101, 111, 119]
14q31	rs4322600	GALC	GPR65	ER + ve ~ ER-ve	[113]
14q32	rs941764	CCDC88C	GPR68, SNORA11B, RPS6KA5, SMEK1, CATSPERB, TC2N	ER + ve	[72]
16q12	rs3803662	intergenic	TNRC9/TOX3, MIR548, CHD9	ER + ve > ER-ve	[95, 101, 103, 107, 111, 124]
16q12	rs17817449, rs11075995	FTO	AKTIP, RBL2, CHD9	ER + ve ~ ER-ve	[72, 115]
16q23	rs13329835	CDYL2	CENPN, ATMIN, GCSH, PKD1L2	ER + ve > ER-ve	[72]
17q22	rs6504950, rs1156287	STXBP4	COX11, HLF	ER + ve > ER-ve	[98, 101]
17q24	rs11077488	intergenic	KCNJ2, KCNJ16	Not mentioned	[110]
18q11	rs527616, rs1436904	CHST9	KCTD1, TAF4B	ER + ve > ER-ve	[72]
19p13	rs8170, rs8100241, rs2363956	BABAM1	ANKLE1	ER-ve	[102, 109, 129]
19p13	rs4808801	ELL	SSBP4, FKBP8, PDE4C	ER + ve ~ ER-ve	[72]
19q13	rs3760982	intergenic	ZNF Cluster, KCNN4, SMG9, XRCC1	ER + ve ~ ER-ve	[72]
19q13	rs10411161, rs3848562	ZNF577	MIR125A, ZNF Cluster	Not mentioned	[105]
20q11	rs2284378	RALY	ASIP, EIF2S2, CHMP4B, ZNF341, E2F1	ER-ve	[109]
21q21	rs2823093	intergenic	NRIP1	ER + ve > ER-ve	[108]
22q12	rs132390	EMID1	KREMEN1, CHEK2, EWSR1, NF2	ER + ve ~ ER-ve	[72]
22q13	rs6001930	MKL1	SGSM3, ADSL, MCHR1, XPNPEP3, DNAJB7, RBX1	ER + ve ~ ER-ve	[72]
22q13	CNV2576, tagged by rs12628403	APOBEC3A- APOBEC3B	APOBEC3C	ER + ve ~ ER-ve	[130]

Legend to Table 2:
72 genomic loci that have been found to harbour low-penetrance breast cancer susceptibility alleles. Genes already mentioned in Table 1 have been excluded although long-range effects remain a possibility. All loci except for CASP8 have been derived from genome-wide association studies. Some chromosomal loci that harbour more than one independent risk variant were here combined when there was a strong overlap of candidate genes. If the variant was within a gene, this is listed separately, although this does not necessarily mean it represents the causal gene. Selected candidate genes in the vicinity (< 1 Mb) are listed in the fourth column. Genes were taken from the GRCh37.p10 primary assembly drawn from the NCBI Genbank (http://www.ncbi.nlm.nih.gov/gene). Association with ER status has been drawn from the original references, and a preponderance of one subtype was assumed if p(het) < 0.05. Note that genome-wide significance has been borderline for some results [106, 110, 113] so that additional validation may be needed for those variants.

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ISSN: 1897-4287

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