Serum gamma-glutamyl transferase level is associated with the risk of pancreatic cystic neoplasms: A nationwide retrospective cohort study

Table 1 Baseline characteristics grouped by gamma-glutamyl transferase level, mean ± SD/n (%)/median (interquartile range)

	Serum GGT level				P value
	Q1 (n = 678027)	Q2 (n = 631006)	Q3 (n = 683678)	Q4 (n = 662954)
Age, years	53.99 ± 11.04	54.34 ± 10.57	54.54 ± 10.3	54.3 ± 9.92	< 0.0001
Sex (male)	330522 (48.75)	326287 (51.71)	335805 (49.12)	336263 (50.72)	< 0.0001
Height, cm	161.72 ± 8.57	161.94 ± 8.75	161.46 ± 8.94	161.51 ± 9.02	< 0.0001
Weight, kg	60.08 ± 9.44	62.32 ± 10.26	63.76 ± 10.8	65.23 ± 11.11	< 0.0001
BMI, kg/m2	22.91 ± 2.68	23.68 ± 2.85	24.37 ± 3.01	24.93 ± 3.2	< 0.0001
Waist circumference, cm	78.19 ± 7.96	80.51 ± 8.32	82.23 ± 8.47	83.94 ± 8.51	< 0.0001
Systolic BP, mmHg	120.82 ± 15.02	123.24 ± 15.11	125.23 ± 15.35	127.69 ± 15.79	< 0.0001
Diastolic BP, mmHg	74.9 ± 9.87	76.57 ± 9.95	77.85 ± 10.12	79.49 ± 10.45	< 0.0001
Income, lowest quartile	139230 (20.53)	126443 (20.04)	137994 (20.18)	135313 (20.41)	< 0.0001
Smoking					< 0.0001
Non-smoker	466617 (68.82)	404113 (64.04)	431045 (63.05)	388541 (58.61)
Ex-smoker	104231 (15.37)	104399 (16.54)	105572 (15.44)	97486 (14.7)
Current	107179 (15.81)	122494 (19.41)	147061 (21.51)	176927 (26.69)
Alcohol consumption					< 0.0001
Non	469136 (69.19)	386982 (61.33)	385451 (56.38)	315205 (47.55)
Mild	192284 (28.36)	214338 (33.97)	244884 (35.82)	243625 (36.75)
Heavy	16607 (2.45)	29686 (4.7)	53343 (7.8)	104124 (15.71)
Regular exercise	141972 (20.94)	129964 (20.6)	135520 (19.82)	123807 (18.68)	< 0.0001
Diabetes mellitus	47748 (7.04)	57860 (9.17)	82847 (12.12)	116527 (17.58)	< 0.0001
Hypertension	159803 (23.57)	187639 (29.74)	245357 (35.89)	284908 (42.98)	< 0.0001
Dyslipidemia	85023 (12.54)	117879 (18.68)	168725 (24.68)	204262 (30.81)	< 0.0001
CKD	50370 (7.43)	50632 (8.02)	59473 (8.7)	57527 (8.68)	< 0.0001
Fasting glucose, mg/dL	95.22 ± 19.82	97.76 ± 22.77	100.74 ± 25.96	106.23 ± 31.61	< 0.0001
Estimated glomerular filtration rate, mL/minute/1.73 m2	85.84 ± 36.4	84.49 ± 38.14	84.33 ± 39.19	84.99 ± 37.51	< 0.0001
Total cholesterol, mg/dL	189.41 ± 33.53	197.61 ± 35.16	202.83 ± 37.04	206.82 ± 40.37	< 0.0001
HDL-C, mg/dL	56.11 ± 29.52	55.6 ± 29.27	55.45 ± 30.01	56.03 ± 29.36	< 0.0001
LDL-C, mg/dL	113.67 ± 35.48	118.38 ± 37.06	119.97 ± 39.03	116.79 ± 42.7	< 0.0001
Triglyceride1, mg/dL	93.37 (93.26-93.48)	109.43 (109.29-109.57)	125.29 (125.13-125.45)	150.01 (149.81-150.22)	< 0.0001
AST1, IU/L	20.97 (20.95-20.98)	22.31 (22.29-22.33)	24 (23.98-24.02)	29.95 (29.92-29.98)	< 0.0001
ALT1, IU/L	16.51 (16.5-16.53)	19.25 (19.23-19.27)	22.47 (22.44-22.49)	30.91 (30.87-30.95)	< 0.0001

¹Variables are presented with geometric mean and 95% confidence interval.

GGT: Gamma-glutamyl transferase; BMI: Body mass index; BP: Blood pressure; HDL-C: High-density lipoprotein cholesterol; CKD: Chronic kidney disease; LDL-C: Low-density lipoprotein cholesterol; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase.

Table 2 Multivariate regression analysis of the risk of pancreatic cystic neoplasm according to quartile

GGT	n	PCN	Duration, years	IR, per 1000 person-years	HR (95%CI)
					Model 11	Model 22	Model 33
Q1	678027	6864	6792685.48	1.01	1 (reference)	1 (reference)	1 (reference)
Q2	631006	6736	6330561.72	1.06	1.053 (1.018-1.089)	1.043 (1.009-1.079)	1.04 (1.005-1.075)
Q3	683678	7649	6860249.12	1.11	1.103 (1.068-1.14)	1.077 (1.043-1.113)	1.065 (1.03-1.102)
Q4	662954	7691	6585301.18	1.17	1.158 (1.121-1.197)	1.148 (1.111-1.185)	1.109 (1.07-1.15)

¹Model 1, not adjusted.

²Model 2, adjusted for age and sex.

³Model 3, adjusted for age, sex, income, body mass index, smoking, drinking, regular exercise, diabetes mellitus, hypertension, dyslipidemia, chronic kidney disease, aspartate aminotransferase, and alanine aminotransferase.

GGT: Gamma-glutamyl transferase; PCN: Pancreatic cystic neoplasm; IR: Incidence rate; HR: Hazard ratio; CI: Confidence interval.

Table 3 Subgroup analysis

Subgroup		GGT	n	PCN	Duration, years	IR, per 1000 person-years	HR (95%CI)
							Univariate	Multivariate
Age	40-64	Q1-Q3	1608646	15427	16422259.06	0.94	1 (reference)	1 (reference)
		Q4	548805	5752	5540769.65	1.04	1.108 (1.075-1.142)	1.046 (1.013-1.081)
	≥ 65	Q1-Q3	384065	5822	3561237.26	1.63	1 (reference)	1 (reference)
		Q4	114149	1939	1044531.53	1.86	1.138 (1.081-1.198)	1.1 (1.044-1.16)
	P value						0.3785	0.0982
Sex	Male	Q1-Q3	992614	9438	9844762.8	0.96	1 (reference)	1 (reference)
		Q4	336263	3081	3304098.27	0.93	0.975 (0.936-1.016)	1.027 (0.984-1.073)
	Female	Q1-Q3	1000097	11811	10138733.52	1.16	1 (reference)	1 (reference)
		Q4	326691	4610	3281202.91	1.40	1.209 (1.168-1.251)	1.091 (1.053-1.131)
	P value						< 0.0001	0.0294
Obesity	No	Q1-Q3	1380869	14468	13822858.61	1.05	1 (reference)	1 (reference)
		Q4	346198	4046	3409592.7	1.19	1.138 (1.099-1.178)	1.091 (1.052-1.131)
	Yes	Q1-Q3	611842	6781	6160637.72	1.10	1 (reference)	1 (reference)
		Q4	316756	3645	3175708.48	1.15	1.044 (1.003-1.087)	1.034 (0.991-1.078)
	P value						0.0016	0.0474
Smoke	Non-ex-smoker	Q1-Q3	1615977	18150	16245614.46	1.12	1 (reference)	1 (reference)
		Q4	486027	6179	4848109.02	1.27	1.143 (1.11-1.176)	1.08 (1.045-1.117)
	Current	Q1-Q3	376734	3099	3737881.86	0.83	1 (reference)	1 (reference)
		Q4	176927	1512	1737192.16	0.87	1.052 (0.99-1.119)	1.035 (0.986-1.087)
	P value						0.0175	0.139
Alcohol consumption	Non	Q1-Q3	1241569	14499	12405702.8	1.17	1 (reference)	1 (reference)
		Q4	315205	4482	3128550.13	1.43	1.227 (1.187-1.269)	1.066 (1.034-1.1)
	Mild	Q1-Q3	651506	5861	6579284.89	0.89	1 (reference)	1 (reference)
		Q4	243625	2243	2430009.54	0.92	1.04 (0.99-1.092)	1.063 (0.998-1.133)
	Heavy	Q1-Q3	99636	889	998508.63	0.89	1 (reference)	0.9352
		Q4	104124	966	1026741.52	0.94	1.061 (0.969-1.163)	1 (reference)
	P value						< 0.0001	1.099 (1.061-1.139)
Regular exercise	No	Q1-Q3	1585255	16599	15878455.3	1.05	1 (reference)	1 (reference)
		Q4	539147	6182	5350376.36	1.16	1.108 (1.076-1.141)	1.007 (0.958-1.059)
	Yes	Q1-Q3	407456	4650	4105041.02	1.13	1 (reference)	1 (reference)
		Q4	123807	1509	1234924.82	1.22	1.081 (1.02-1.146)	1.04 (0.949-1.14)
	P value						0.4652	0.0129
Diabetes mellitus	No	Q1-Q3	1804256	18402	18175069.52	1.01	1 (reference)	1 (reference)
		Q4	546427	6069	5462111.66	1.11	1.1 (1.068-1.132)	1.07 (1.037-1.104)
	Yes	Q1-Q3	188455	2847	1808426.8	1.57	1 (reference)	1 (reference)
		Q4	116527	1622	1123189.52	1.44	0.916 (0.862-0.974)	1.048 (0.988-1.112)
	P value						< 0.0001	0.5253
Hypertension	No	Q1-Q3	1399912	13423	14178760.31	0.95	1 (reference)	1 (reference)
		Q4	378046	3939	3795697.71	1.04	1.099 (1.06-1.138)	1.09 (1.057-1.124)
	Yes	Q1-Q3	592799	7826	5804736.01	1.35	1 (reference)	1 (reference)
		Q4	284908	3752	2789603.47	1.34	0.998 (0.96-1.038)	0.966 (0.907-1.027)
	P value						0.0003	0.0004
Dyslipidemia	No	Q1-Q3	1621084	16422	16279851.44	1.01	1 (reference)	1 (reference)
		Q4	458692	5021	4548820.32	1.10	1.098 (1.063-1.133)	1.08 (1.04-1.121)
	Yes	Q1-Q3	371627	4827	3703644.88	1.30	1 (reference)	1 (reference)
		Q4	204262	2670	2036480.86	1.31	1.006 (0.96-1.055)	1.049 (1.008-1.093)
	P value						0.0027	0.2891
CKD	No	Q1-Q3	1832236	19256	18437941.67	1.04	1 (reference)	1 (reference)
		Q4	605427	6939	6034294.22	1.15	1.104 (1.074-1.134)	1.082 (1.046-1.119)
	Yes	Q1-Q3	160475	1993	1545554.65	1.29	1 (reference)	1 (reference)
		Q4	57527	752	551006.96	1.36	1.06 (0.975-1.153)	1.032 (0.983-1.083)
	P value						0.3681	0.1029
AST	Q1-Q3	Q1-Q3	1650419	17091	16572543.55	1.03	1 (reference)	1 (reference)
		Q4	344868	3883	3457375.59	1.12	1.09 (1.052-1.128)	1.073 (1.041-1.105)
	Q4	Q1-Q3	342292	4158	3410952.77	1.22	1 (reference)	1 (reference)
		Q4	318086	3808	3127925.59	1.22	1.002 (0.959-1.047)	1.006 (0.924-1.094)
	P value						0.0033	0.1532
ALT	Q1-Q3	Q1-Q3	1685780	17657	16887579.08	1.05	1 (reference)	1 (reference)
		Q4	320867	3680	3178308.55	1.16	1.11 (1.072-1.15)	1.087 (1.048-1.127)
	Q4	Q1-Q3	306931	3592	3095917.24	1.16	1 (reference)	1 (reference)
		Q4	342087	4011	3406992.64	1.18	1.017 (0.973-1.064)	1.006 (0.96-1.053)
	P value						0.0028	0.0085

GGT: Gamma-glutamyl transferase; PCN: Pancreatic cystic neoplasm; IR: Incidence rate; HR: Hazard ratio; CI: Confidence interval; CKD: Chronic kidney disease; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase.