Homozygous deletions of UGT2B17 modifies effects of smoking on TP53-mutations and relapse of head and neck carcinoma

Table 2 Effects modifiers of smoking on TP53 -mutations in tumors ^*1

Outcome: any type ofTP53-mutations	P _interaction ^*2	Smokers N = 167	Non-smokers N = 65	RR	95% CI	p-value
Primary sites of tumor – no. (%)*6	0.09
Oropharyngeal		26 (76)	4 (80)	0.96	0.59 to 1.54	0.86
Hypopharyngeal		37 (79)	11 (69)	1.15	0.80 to 1.64	0.42
Laryngeal		14 (58)	3 (60)	0.97	0.44 to 2.15	0.95
Oral		15 (48)	16 (67)	0.73	0.46 to 1.15	0.18
Nasal		10 (91)	1 (11)	8.18	1.28 to 52.4	0.0004
Stages – no. (%)	0.0019
I		7 (64)	1 (100)	0.64	0.41 to 0.99	0.46
II		19 (56)	10 (71)	0.78	0.50 to 1.22	0.32
III		21 (75)	9 (45)	1.67	0.98 to 2.83	0.034
IV		60 (69)	17 (49)	1.42	0.98 to 2.05	0.035
UGT2B17 CNVs^*5 – no. (%)	0.0016
UGT2B17-deletion: 0 copy		85 (69)	24 (44)	1.57	1.14 to 2.17	0.0016
UGT2B17-presence: 1 copy or 2 copies		16 (53)	11 (79)	0.68	0.44 to 1.05	0.11
CDKN2A SCNA^36 – no. (%)	0.08
Normal: 2 copies		68 (65)	22 (51)	1.27	0.91 to 1.75	0.12
Heterozygous deletion: 1 copy		21 (78)	7 (70)	1.11	0.71 to 1.75	0.62
Homozygous deletions: 0 copy		6 (75)	4 (100)	0.75	0.50 to 1.12	0.27
p16-ICH in tumor^46 – no. (%)	0.043
p16 (-)		85 (68)	33 (66)	1.03	0.82 to 1.30	0.80
p16 (+)		17 (77)	2 (22)	3.48	1.00 to 12.1	0.0043
UGT2B17-CNVs & p16-ICH – no. (%)^*6	0.0080
UGT2B17-presence & p16 (-)		13 (57)	10 (91)	0.62	0.42 to 0.93	0.045
UGT2B17-deletions & p16 (-)		67 (69)	21 (57)	1.22	0.89 to 1.66	0.18
UGT2B17-presence & p16 (+)		2 (50)	1 (33)	1.50	0.23 to 9.80	0.66
UGT2B17-deletions & p16 (+)		13 (81)	1 (17)	4.88	0.80 to 29.6	0.0050

^*1Any type of TP53-mutations observed in the tumor genome was used as the outcome.
^*2P_interaction was calculated as interaction effect between a factor and smoking on the risk of TP53-mutations in a tumor. With the Bonferroni correction, p < 0.005 was considered as statistically significant.
^*3CDKN2A SCNA: Copy number alterations of CDKN2A, which encodes p16, were determined by CGH array.
^*4p16 overexpression in tumor samples was determined via ICH and classified as positive (+) or negative (-).
^*5UGT2B17 CNV: Copy number variants of UGT2B17 were screened via CGH array and confirmed by real-time PCR and PCR to differentiate between one and two copies of UGT2B17-gene.
^*6Interaction was analyzed except for HPV-positive patients.

ISSN: 1471-2407