Dysregulation of the homeobox transcription factor gene HOXB13: role in prostate cancer

Figures & data

Table 1 HOXB13 risk allele studies cited in this review

Study	Study design	Population	Number of subjects	Case carrier frequency	Risk estimate	95% CI	P-value	Comments
Ewing et al^Citation36	Population-based case–control	US	6,484	1.40%	OR =20.1	3.5–803.3	<0.001	Association with family history, early diagnosis
Stott-Miller et al^Citation43	Population-based case–control	US	2,569	1.30%	RR =3.3	1.2–9.0		Association with family history
Lin et al^Citation51	Population-based case–control	People’s Republic of China	2,111	0.35%			0.027	G84e allele not observed; alternate risk variant proposed for Chinese population
Karlsson et al^Citation48	Population-based case–control	Sweden	9,696	4.30%–4.60%	RR =3.4	2.2–5.4	<0.001	Control population had a carrier rate of 1.3%
Witte^Citation44	Aggressive disease case–control	US	1,540	0.81%	OR =4.8*		0.01	Association with early diagnosis
Ewing^Citation36	Family-based case–control	US	1,486	4.70%	OR =68.1		<0.001
Witte^Citation44	Family-based case–control	US	1,134	1.89%	OR =4.8*		0.01	Association with early diagnosis
Breyer et al^Citation45	Family-based case–control	US	1,858	1.90%	OR =7.9	1.8–34.5	0.0062	Association with family history
Xu^Citation46	Family-based case–control	Multiple	2,443 families	4.60% of families	OR =4.4	2.6–7.5	<0.001	51% of cases from carrier families harbored risk allele
Schroeck et al^Citation49	Biopsied subjects cohort	US	948	0.42%				G84E variant has low utility at time of diagnostic biopsy
Chen et al^Citation50	Cohort	Multiple	3,508	0.99%	RR =2.5	1.5–4.1	0.01	Allele detected only in Caucasians
MacInnis^Citation47	Population-based families	Australia	1,384	1.40%	RR =16.4	2.5–107.2		Estimated penetrance of 60% by age 80 years

Note:

* OR for both sibling and case–control arms.

Abbreviations: CI, confidence interval; OR, odds ratio; RR, relative risk.

Figure 1 The genomic architecture of HOX genes and schematic of gene expression in embryonic development.

Notes: (A) Humans have four clusters of HOX genes on different chromosomes, labeled Cluster A through Cluster D. Each cluster comprises a variable subset of the 13 homology-based HOX gene subtypes. The relative order of the subtypes is preserved across clusters. This conserved ordering is attributed to the genomic duplication-based mechanism by which the clusters arose. (B) During embryonic development, HOX genes are expressed sequentially in partially overlapping zones along the anterior-posterior axis, a phenomenon called collinearity. Accordingly, HOX13 paralogs, including HOXB13, are expressed in posterior regions of the embryo and direct development of the spinal cord, digestive tract, and urogenital system.
Abbreviation: HOX, homeobox gene.

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