The association between HLA and non-Hodgkin lymphoma subtypes, among a transplant-indicated population

Figures & data

Table 1. Distribution of hematopoietic malignancies indicated for bone marrow transplant at the City of Hope 1995–2015 and potential donors (controls without cancer) for whom high resolution HLA haplotyping was imputed.

	Caucasian		Hispanic		Asian		African American
	N	Age (median)	N	Age (median)	N	Age (median)	N	Age (median)
B-cell NHL	780	49	172	46	100	50	40	46
DLBCL	229	50	68	47	45	52	12	33
FL	191	47	49	46	18	43	<10	46
CLL/SLL	124	51	12	53	–	–	<10	41
Mantle	120	54	25	57	20	56	<10	55
Other B-cell^a	116	46	18	48	17^c	47	<10	48
T-cell NHL	158	48	64	36	38	50	16	47
PTCL	87	48	32	44	22	51	–	–
Other T-cell^b	71	43	32	29	16	45	16^c	47
Gender	N	%	N	%	N	%	N	%
Male	599	63.9%	153	64.8%	78	57.4%	39	69.6%
Female	339	36.1%	83	35.2%	58	42.6%	17	30.4%
Donors	6801	40	2076	39	1029	39	365	42

a Burkitt's lymphoma, marginal zone lymphoma, lymphoplasmacytic lymphoma, Waldenstrom macroglobulinemia, NHL – not otherwise specified.

b Mycosis Fungoides/Sézary syndrome, pre-T cell, natural killer (NK) T-cell, adult T-cell leukemia/lymphoma, histiocytic T-cell, T-cell not otherwise specified.

c Includes other subtypes listed above for patient confidentiality.

DLBCL: diffuse large B-cell lymphoma; FL: follicular lymphoma; CLL/SLL: chronic lymphocytic leukemia/small lymphocytic lymphoma; PTCL: peripheral T-cell lymphoma.

Table 2. HLA haplotype association with B-cell NHL subtypes (DLBCL, FL, and MCL), in Caucasian patients and donors (analyses adjusted for sex and age, associations significant after multiple testing correcting in bold italics).

	Patient (%)	Donor (%)	OR	95% CI	p value
DLBCL	n = 229	n = 6801
A*01:01∼C*07:01∼B*08:01∼DRB1*03:01∼DQB1*02:01	7.2%	7.2%	1.14	(0.67–1.93)	.63
A*03:01∼C*07:02∼B*07:02∼DRB1*15:01∼DQB1*06:02	4.1%	4.3%	1.01	(0.5–2.05)	.86
A*29:02∼C*16:01∼B*44:03∼DRB1*07:01∼DQB1*02:01	3.2%	2.4%	1.48	(0.67–3.29)	.36
A*30:01∼C*06:02∼B*13:02∼DRB1*07:01∼DQB1*02:01	2.1%	1.6%	1.38	(0.46–4.1)	.29
A*03:01∼C*04:01∼B*35:01∼DRB1*01:01∼DQB1*05:01	3.7%	1.5%	2.70	(1.21–6.01)	.04
A*02:01∼C*07:01∼B*08:01∼DRB1*03:01∼DQB1*02:01	3.1%	1.1%	3.27	(1.46–7.32)	.016
A*26:01∼C*12:03∼B*38:01∼DRB1*04:02∼DQB1*03:02	3.0%	1.1%	3.06	(1.34–6.97)	.01
A*01:01	24.3%	23.5%	1.11	(0.81–1.52)	.5
A*02:01	46.0%	49.0%	0.94	(0.72–1.24)	.7
A*03:01	22.6%	22.8%	0.99	(0.72–1.37)	1
A*26:01	9.7%	7.4%	1.30	(0.83–2.06)	.3
A*29:02	6.6%	5.7%	1.20	(0.7–2.08)	.5
A*30:01	3.1%	2.9%	1.11	(0.51–2.42)	.8
B*07:02	17.5%	21.7%	0.79	(0.56–1.12)	.2
B*08:01	15.0%	15.2%	1.06	(0.73–1.55)	.8
B*13:02	8.3%	4.8%	1.99	(1.21–3.26)	.007
B*35:01	10.5%	11.9%	0.89	(0.57–1.37)	.6
B*38:01	8.3%	5.1%	1.52	(0.92–2.49)	.1
B*44:03	9.6%	8.7%	1.13	(0.72–1.79)	.6
C*04:01	22.9%	22.1%	0.76	(0.54–1.06)	.1
C*06:02	23.5%	14.9%	1.72	(1.24–2.4)	.001
C*07:01	17.4%	23.2%	0.71	(0.49–1.02)	.06
C*07:02	19.7%	24.5%	0.80	(0.57–1.14)	.2
C*12:03	13.6%	10.4%	1.26	(0.84–1.9)	.3
C*16:01	7.5%	5.8%	1.32	(0.77–2.24)	.3
DRB1*01:01	16.0%	13.5%	1.20	(0.82–1.75)	.34
DRB1*03:01	16.0%	17.9%	0.98	(0.67–1.42)	.9
DRB1*04:02	4.6%	3.0%	1.40	(0.72–2.74)	.3
DRB1*07:01	23.3%	22.9%	1.03	(0.75–1.43)	.9
DRB1*15:01	17.8%	23.0%	0.70	(0.49–1)	.05
DQB1*02:01	34.4%	35.0%	1.03	(0.76–1.4)	.9
DQB1*03:02	16.7%	21.1%	0.82	(0.56–1.21)	.3
DQB1*05:01	26.6%	22.0%	1.19	(0.86–1.66)	.3
DQB1*06:02	17.7%	22.2%	0.74	(0.51–1.09)	.1
FL	n = 191	n = 6801
A*01:01∼C*07:01∼B*08:01∼DRB1*03:01∼DQB1*02:01	7.2%	7.2%	1.13	(0.64–1.97)	.68
A*29:02∼C*16:01∼B*44:03∼DRB1*07:01∼DQB1*02:01	4.4%	2.4%	2.01	(0.96–4.22)	.1
A*23:01∼C*04:01∼B*44:03∼DRB1*07:01∼DQB1*02:01	3.0%	1.1%	2.69	(0.95–7.58)	.17
A*02:01∼C*06:02∼B*13:02∼DRB1*07:01∼DQB1*02:01	2.8%	1.1%	2.70	(1.09–6.66)	.04
A*01:01	28.0%	23.5%	1.33	(0.96–1.85)	.09
A*02:01	48.4%	49.0%	1.02	(0.76–1.37)	.9
A*23:01	7.7%	3.9%	1.90	(1.07–3.34)	.03
A*29:02	10.4%	5.7%	1.97	(1.2–3.22)	.007
B*08:01	17.6%	15.2%	1.29	(0.86–1.93)	.2
B*13:02	9.4%	4.8%	2.21	(1.30–3.77)	.004
B*44:03	14.1%	8.7%	1.77	(1.13–2.76)	.01
C*04:01	26.8%	26.9%	0.98	(0.68–1.41)	.9
C*06:02	24.8%	14.9%	1.86	(1.27–2.71)	.001
C*16:01	9.8%	5.8%	1.81	(1.04–3.14)	.04
DRB1*03:01	16.8%	17.9%	1.02	(0.67–1.54)	.9
DRB1*07:01	41.3%	22.9%	2.41	(1.75–3.31)	<.0001
DQB1*02:01	45.3%	35.0%	1.63	(1.16–2.3)	.005
MCL	n = 120	n = 6801
A*01:01∼C*07:01∼B*08:01∼DRB1*03:01∼DQB1*02:01	8.2%	7.2%	1.42	(0.72–2.80)	.37
A*03:01∼C*07:02∼B*07:02∼DRB1*15:01∼DQB1*06:02	4.8%	4.3%	1.10	(0.43–2.79)	.7
A*02:01∼C*03:04∼B*15:01∼DRB1*04:01∼DQB1*03:02	2.1%	2.0%	1.20	(0.30–4.81)	.8
A*26:01∼C*12:03∼B*38:01∼DRB1*04:02∼DQB1*03:02	3.0%	1.1%	3.13	(1.00–9.83)	.06
A*01:01	30.6%	23.5%	1.60	(1.05–2.43)	.03
A*02:01	46.8%	49.0%	1.03	(0.7–1.51)	.9
A*03:01	18.0%	22.8%	0.69	(0.42–1.14)	.2
A*26:01	9.0%	7.4%	1.24	(0.63–2.44)	.5
B*07:02	12.5%	21.7%	0.98	(0.61–1.59)	.9
B*08:01	17.8%	15.2%	1.28	(0.76–2.14)	.4
B*15:01	11.2%	10.6%	1.14	(0.61–2.11)	.7
B*38:01	6.5%	5.1%	1.04	(0.46–2.34)	.9
C*03:04	15.0%	12.5%	1.46	(0.83–2.58)	.19
C*07:01	33.0%	23.2%	1.65	(1.07–2.54)	.02
C*07:02	19.0%	24.5%	0.76	(0.45–1.27)	.3
C*12:03	10.0%	10.4%	0.84	(0.43–1.66)	.6
DRB1*03:01	25.0%	17.9%	1.68	(1.05–2.67)	.03
DRB1*04:01	17.3%	14.3%	1.47	(0.86–2.49)	.2
DRB1*04:02	5.8%	3.0%	1.82	(0.76–4.33)	.2
DRB1*08:01	6.7%	4.3%	1.43	(0.64–3.18)	.4
DQB1*02:01	37.4%	35.0%	1.15	(0.74–1.78)	.5
DQB1*03:02	20.9%	21.1%	1.25	(0.74–2.12)	.4
DQB1*06:02	15.4%	22.2%	0.57	(0.32–1.03)	.06

DLBCL: diffuse large B-cell lymphoma; FL: follicular lymphoma; MCL: mantle cell lymphoma.

Bold-italics indicate alleles significant after false discovery rate correction.

Table 3. Effect of homozygosity at the three HLA class I loci-A, -B, and -C and three HLA class II loci-DRB1, DQB1, and DPB1 on susceptibility to three B-cell NHL subtypes (DLBCL, FL, and MCL) in Caucasian patients and donors (analyses adjusted for sex and age).

		Donors (n = 6801)	DLBCL (n = 229)		FL (n = 191)		MCL (n = 120)
		%	%	OR (95% CI)	%	OR (95% CI)	%	OR (95% CI)
Class I locus
HLA-A	Heterozygote	84.5%	82.5%	1.00 (REF)	86.4%	1.00 (REF)	81.7%	1.00 (REF)
	Homozygote	15.5%	17.5%	1.18 (0.83–1.68)	13.6%	0.87 (0.57–1.33)	18.3%	1.26 (0.78–2.04)
HLA-B	Heterozygote	93.7%	92.1%	1.00 (REF)	90.6%	1.00 (REF)	90.8%	1.00 (REF)
	Homozygote	6.3%	7.9%	1.27 (0.78–2.10)	9.4%	1.54 (0.93–2.53)	9.2%	1.43 (0.75–2.73)
HLA-C	Heterozygote	89.8%	87.3%	1.00 (REF)	87.4%	1.00 (REF)	87.5%	1.00 (REF)
	Homozygote	10.2%	12.7%	1.28 (0.86–1.92)	12.6%	1.26 (0.81–1.95)	12.5%	1.23 (0.70–2.15)
Total # of homozygote loci	0	75.5%	72.5%	1.00 (REF)	75.4%	1.00 (REF)	72.5%	1.00 (REF)
	1	18.6%	20.5%	1.17 (0.84–1.63)	16.2%	0.89 (0.60–1.31)	18.3%	1.06 (0.65–1.71)
	2+	5.9%	7.0%	1.26 (0.75–2.15)	8.4%	1.43 (0.84–2.43)	9.2%	1.62 (0.84–3.11)
	p-trend			.84		.18		.5
Class II locus
HLA-DRB1	Heterozygote	91.9%	85.9%	1.00 (REF)	91.9%	1.00 (REF)	93.3%	1.00 (REF)
	Homozygote	8.1%	14.1%	1.89 (1.28–2.79)	8.1%	2.06 (1.37–3.09)	6.7%	0.80 (0.38–1.66)
HLA-DQB1	Heterozygote	86.0%	76.1%	1.00 (REF)	86.0%	1.00 (REF)	85.0%	1.00 (REF)
	Homozygote	14.0%	23.9%	1.46 (1.04–2.06)	14.0%	1.50 (1.04–2.16)	15.0%	1.09 (0.65–1.83)
HLA-DPB1^a	Heterozygote	75.8%	74.8%	1.00 (REF)	80.3%	1.00 (REF)	80.5%	1.00 (REF)
	Homozygote	24.2%	25.2%	1.03 (0.65–1.62)	19.7%	0.76 (0.42–1.37)	19.5%	0.71 (0.31–1.61)
Total # of homozygote loci^a	0	65.1%	62.6%	1.00 (REF)	73.2%	1.00 (REF)	70.7%	1.00 (REF)
	1	26.3%	26.2%	1.06 (0.67–1.68)	15.5%	0.53 (0.27–1.02)	26.8%	0.97 (0.47–2.03)
	2+	8.6%	11.2%	1.60 (0.84–3.07)	11.3%	1.30 (0.61–2.79)	2.4%	0.33 (0.04–2.48)
	p-trend			.49		.03		.39

a Restricted to those with DPB molecular typing: 4594 Donors, 107 DLBCL, 74 FL, and 41 MCL.

DLBCL: diffuse large B-cell lymphoma; FL: follicular lymphoma; MCL: mantle cell lymphoma.

Values in bold are significant at a p-value of .05.