Use of phthalate-containing prescription drugs and the risk of gastric cancer: a Danish nationwide case-control study

Figures & data

Figure 1. Flowchart displaying case selection.

Table 1. Characteristics of cases of gastric adenocarcinoma and matched population based controls.

	Cases	Controls
All	(n = 1525)	(n = 15,250)
Male gender	1099 (72.1%)	10,990 (72.1%)
Age
Median (IQR, years)	68 (60–76)	68 (60–76)
<50 years	121 (7.9%)	1210 (7.9%)
50–69 years	700 (45.9%)	7000 (45.9%)
70+ years	704 (46.2%)	7040 (46.2%)
Cancer localization
Cardia	762 (50.0%)	–
Corpus	481 (31.5%)	–
Unknown	282 (18.5%)	–
Ortho-phthalate exposure
Never	1291 (84.7%)	13,101 (85.9%)
0–249 mg	186 (12.2%)	1763 (11.6%)
250–499 mg	13 (0.9%)	133 (0.9%)
≥500 mg	35 (2.3%)	253 (1.7%)
Drug use
Low-dose aspirin	424 (27.8%)	3848 (25.2%)
Non-aspirin NSAID’s	813 (53.3%)	7624 (50.0%)
HRT	155 (10.2%)	1708 (11.2%)
Comorbidities
Diabetes	110 (7.2%)	997 (6.5%)
COPD	81 (5.3%)	637 (4.2%)
Alcohol-related diseases	98 (6.4%)	619 (4.1%)
H. pylori infection	620 (40.7%)	4793 (31.4%)
Chronic atrophic gastritis	26 (1.7%)	149 (1.0%)
Duodenal ulcers	23 (1.5%)	206 (1.4%)
Pernicious anemia	–	–
Education
Short (7–10 years)	619 (40.6%)	4977 (32.6%)
Medium (11–13 years)	579 (38.0%)	5960 (39.1%)
Long (>13 years)	254 (16.7%)	3595 (23.6%)
Unknown	73 (4.8%)	718 (4.7%)

IQR: inter quartile range; NSAID’s: non-steroid anti-inflammatory drugs; HRT: hormonal replacement therapy; COPD: chronic obstructive pulmonary disease.

Table 2. Association between ortho-phthalate exposure or enteric phthalate polymer exposure and the risk of gastric adenocarcinoma within dose strata throughout the period 2004–2015.

	Cases	Controls	Crude OR^a	Adjusted OR^b
Never exposed	1220	12,482	1.0 (ref.)	1.0 (ref.)
Ortho-phthalates
Ever exposed	234	2149	1.12 (0.96–1.30)	1.00 (0.86–1.16)
0–249 mg	186	1763	1.08 (0.92–1.27)	0.97 (0.82–1.15)
250–499 mg	13	133	1.04 (0.58–1.87)	0.91 (0.50–1.64)
>500 mg	35	253	1.44 (1.00–2.08)	1.22 (0.84–1.77)
DEP
0–249 mg	183	1718	1.09 (0.93–1.28)	0.99 (0.83–1.17)
250–499 mg	11	120	0.99 (0.53–1.86)	0.89 (0.47–1.68)
>500 mg	18	142	1.27 (0.77–2.10)	1.06 (0.63–1.76)
DBP
0–249 mg	8	85	1.05 (0.50–2.19)	0.92 (0.44–1.94)
250–499 mg	(n < 5)	13	(−)	(−)
>500 mg	17	117	1.53 (0.91–2.58)	1.32 (0.78–2.23)
Enteric phthalate polymers
Ever exposed	224	2081	1.11 (0.95–1.29)	1.00 (0.85–1.17)
0–4999 mg	174	1563	1.16 (0.98–1.37)	1.04 (0.88–1.24)
5000–9999 mg	17	146	1.12 (0.67–1.88)	1.03 (0.61–1.73)
>10,000 mg	33	372	0.89 (0.61–1.27)	0.79 (0.54–1.16)
CAP
0–1999 mg	121	1176	1.06 (0.87–1.29)	0.96 (0.79–1.18)
2000–3999 mg	19	199	1.01 (0.62–1.64)	0.88 (0.54–1.43)
>4000	43	457	0.93 (0.67–1.29)	0.87 (0.62–1.22)
HPMCP
0–1999 mg	121	1176	1.06 (0.87–1.29)	0.96 (0.79–1.18)
2000–3999 mg	19	199	1.01 (0.62–1.64)	0.88 (0.54–1.43)
>4000	43	457	0.93 (0.67–1.29)	0.87 (0.62–1.22)
PVAP
0–9999 mg	(n < 5)	17	(−)	(−)
10,000–19,999 mg	(n < 5)	(n < 5)	(−)	(−)
>20,000 mg	(n < 5)	21	(−)	(−)

Ortho-phthalate exposure is specified to diethyl phthalate (DEP) and dibutyl phthalate (DBP) exposure. Enteric phthalate polymers are specified to cellulose acetate phthalate (CAP), hydroxypropylmethylcellulose phthalate (HPMCP) and polyvinyl acetate phthalate (PVAP).

^a Adjusted for age, calendar time and gender (by matched design).

^b Fully adjusted model, see section ‘Confounding variables’.

Table 3. Subgroup analysis.

	Cases exposed/unexposed	Controls exposed/unexposed	Crude OR^a	Adjusted OR^b
All	234/1220	2149/12,482	1.12 (0.96–1.30)	1.00 (0.86–1.16)
Age
<50 years	18/102	152/1050	1.21 (0.71–2.07)	1.04 (0.59–1.82)
50–69 years	97/578	917/5882	1.07 (0.85–1.34)	0.93 (0.74–1.18)
>70 years	119/540	1080/5550	1.15 (0.93–1.41)	1.05 (0.84–1.30)
Gender
Male	165/886	1428/9083	1.18 (0.99–1.41)	1.06 (0.88–1.27)
Female	69/334	721/3399	0.98 (0.75–1.29)	0.88 (0.66–1.16)
Stage of disease
Localized	31/148	279/1552	1.18 (0.78–1.78)	1.07 (0.70–1.65)
Non-localized	165/906	1540/9188	1.09 (0.91–1.30)	0.98 (0.82–1.17)
Unknown	38/166	330/1742	1.20 (0.83–1.74)	1.01 (0.68–1.49)
Other subgroups
Excluding those w. lithium exp	228/1198	2087/12,058	1.09 (0.94–1.27)	0.99 (0.85–1.16)
Excluding those w. diabetes	208/1144	1945/11,750	1.10 (0.94–1.29)	0.98 (0.84–1.16)
Excluding those w. alcohol abuse	217/1148	2025/12,044	1.12 (0.96–1.31)	1.02 (0.87–1.20)
Excluding those w. H. pylori	103/765	1203/8902	1.01 (0.81–1.26)	0.92 (0.73–1.15)

^a Adjusted for age, calendar time and gender (by matched design).

^b Fully adjusted model, see section ‘Confounding variables’.