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. 2020 Apr 27;8(5):e649–e660. doi: 10.1016/S2214-109X(20)30059-0

Table 3.

Dose–response associations between different routes of opium use and the risk of developing different cancers

Never used this route First quartile Second quartile Third quartile Fourth quartile Ptrend
All cancers combined (n=1833)
Any route (n=482) 1 (ref) 1·24 (1·01–1·53) 1·22 (0·99–1·51) 1·43 (1·18–1·75) 1·70 (1·42–2·04) <0·0001
Smoking (n=322) 1 (ref) 1·12 (0·88–1·43) 1·00 (0·77–1·30) 1·33 (1·07–1·67) 1·64 (1·33–2·02) <0·0001
Ingestion (n=201) 1 (ref) 1·20 (0·88–1·64) 1·53 (1·16–2·02) 1·41 (1·05–1·91) 1·49 (1·14–1·95) <0·0001
Gastrointestinal cancers combined (n=914)
Any route (n=242) 1 (ref) 1·28 (0·96–1·70) 1·19 (0·89–1·60) 1·28 (0·97–1·70) 1·48 (1·14–1·91) 0·0007
Smoking (n=162) 1 (ref) 1·32 (0·96–1·81) 0·99 (0·68–1·42) 1·22 (0·89–1·69) 1·44 (1·06–1·95) 0·014
Ingestion (n=99) 1 (ref) 1·07 (0·68–1·68) 1·35 (0·90–2·00) 1·33 (0·88–2·01) 1·30 (0·88–1·90) 0·033
Respiratory cancers combined (n=154)
Any route (n=80) 1 (ref) 1·14 (0·54–2·40) 2·38 (1·37–4·11) 2·26 (1·30–3·92) 3·22 (2·02–5·14) <0·0001
Smoking (n=53) 1 (ref) 0·29 (0·07–1·20) 1·42 (0·73–2·76) 1·76 (0·98–3·14) 2·83 (1·77–4·52) 0·0001
Ingestion (n=36) 1 (ref) 2·16 (1·04–4·48) 2·63 (1·39–4·97) 1·19 (0·48–2·96) 1·94 (1·03–3·68) 0·0081
Oesophageal cancer (n=342)
Any route (n=93) 1 (ref) 1·34 (0·84–2·12) 1·18 (0·73–1·91) 1·42 (0·90–2·21) 1·60 (1·06–2·42) 0·0099
Smoking (n=65) 1 (ref) 1·34 (0·78–2·31) 1·00 (0·54–1·85) 1·62 (1·00–2·61) 1·79 (1·12–2·86) 0·0046
Ingestion (n=37) 1 (ref) 1·34 (0·71–2·54) 1·05 (0·51–2·14) 1·53 (0·83–2·84) 0·91 (0·44–1·87) 0·527
Gastric cancer (n=308)
Any route (n=90) 1 (ref) 1·33 (0·83–2·13) 1·57 (1·01–2·43) 1·19 (0·73–1·94) 1·37 (0·88–2·11) 0·067
Smoking (n=62) 1 (ref) 1·53 (0·93–2·53) 1·63 (1·00–2·66) 0·93 (0·50–1·72) 1·27 (0·75–2·16) 0·215
Ingestion (n=34) 1 (ref) 0·75 (0·30–1·83) 1·42 (0·74–2·70) 1·33 (0·67–2·62) 1·16 (0·60–2·23) 0·320
Lung cancer (n=116)
Any route (n=57) 1 (ref) 1·15 (0·49–2·73) 2·34 (1·23–4·43) 2·04 (1·05–3·95) 3·19 (1·85–5·50) <0·0001
Smoking (n=37) 1 (ref) 0·40 (0·09–1·64) 1·16 (0·50–2·72) 1·71 (0·86–3·38) 2·73 (1·57–4·75) 0·0006
Ingestion (n=27) 1 (ref) 2·70 (1·23–5·93) 2·74 (1·30–5·79) 1·35 (0·48–3·74) 1·85 (0·85–4·02) 0·024
Colon cancer (n=95)
Any route (n=15) 1 (ref) 1·58 (0·71–3·51) 0·49 (0·11–2·06) 0·74 (0·22–2·44) 0·66 (0·19–2·25) 0·379
Smoking (n=10) 1 (ref) 1·75 (0·75–4·11) .. 0·92 (0·28–3·00) 0·33 (0·04–2·47) 0·226
Ingestion (n=5) 1 (ref) 0·73 (0·10–5·31) 1·49 (0·35–6·18) .. 1·47 (0·34–6·27) 0·994
Brain cancer (n=80)
Any route (n=17) 1 (ref) 0·28 (0·03–2·05) 2·08 (0·95–4·58) 0·83 (0·25–2·76) 1·33 (0·48–3·63) 0·476
Smoking (n=8) 1 (ref) 0·32 (0·04–2·37) 0·95 (0·29–3·11) 0·59 (0·14–2·49) 0·68 (0·16–2·94) 0·383
Ingestion (n=10) 1 (ref) .. 3·88 (1·51–9·94) 1·89 (0·45–7·97) 2·70 (0·79–9·20) 0·017
Pancreatic cancer (n=78)
Any route (n=22) 1 (ref) 0·91 (0·28–2·97) 1·50 (0·58–3·90) 1·19 (0·41–3·43) 2·66 (1·23–5·74) 0·028
Smoking (n=16) 1 (ref) 0·80 (0·19–3·31) 1·25 (0·38–4·10) 1·52 (0·53–4·31) 2·82 (1·21–6·60) 0·028
Ingestion (n=8) 1 (ref) 0·64 (0·08–4·69) 1·87 (0·57–6·13) .. 2·36 (0·81–6·87) 0·347
Liver cancer (n=73)
Any route (n=20) 1 (ref) 1·08 (0·38–3·04) 0·76 (0·23–2·53) 1·25 (0·48–3·27) 1·76 (0·77–4·01) 0·254
Smoking (n=8) 1 (ref) 0·61 (0·14–2·53) .. 0·81 (0·25–2·65) 0·84 (0·25–2·79) 0·340
Ingestion (n=12) 1 (ref) 2·29 (0·70–7·44) 1·37 (0·32–5·75) 1·54 (0·36–6·50) 3·37 (1·27–8·92) 0·018
Bladder cancer (n=47)
Any route (n=23) 1 (ref) 3·24 (1·28–8·20) 0·55 (0·07–4·21) 3·31 (1·27–8·59) 4·28 (1·81–10·15) 0·0009
Smoking (n=14) 1 (ref) 2·61 (0·99–6·87) .. 1·53 (0·45–5·16) 2·62 (1·01–6·80) 0·107
Ingestion (n=10) 1 (ref) 1·05 (0·14–7·84) 2·83 (0·84–9·52) 2·05 (0·47–8·84) 3·12 (1·01–9·60) 0·018
Laryngeal cancer (n=38)
Any route (n=23) 1 (ref) 1·11 (0·24–5·01) 2·55 (0·87–7·42) 2·98 (1·08–8·22) 3·34 (1·33–8·34) 0·0004
Smoking (n=16) 1 (ref) .. 2·19 (0·73–6·55) 1·99 (0·66–6·01) 3·15 (1·30–7·58) 0·0006
Ingestion (n=9) 1 (ref) 0·87 (0·11–6·52) 2·31 (0·68–7·79) 0·79 (0·10–5·94) 2·08 (0·68–6·38) 0·206

Data are adjusted hazard ratio (95% CI), unless otherwise indicated. This model used age as the timescale and was adjusted for sex (male vs female), ethnicity (Turkman vs non-Turkman), residence (urban vs rural), wealth score quartiles, smoking cigarettes (ever vs never), cumulative pack-years of smoked cigarettes (continuous variable), and regular alcohol drinking (never vs ever). For participants who used opium via both routes, we calculated the amount of opium used through each route separately; therefore, the numbers in each category of smoking and ingestion routes do not sum to the number of any route because these categories also include the few dual-route opium users. The amount of opium was calculated as nokhod-years. In each quartile, the cumulative opium used through the presented routes was as follows: any route, first quartile (≤5), second quartile (5·1–21), third quartile (21·1–60), and fourth quartile (>60); opium smoking, first quartile (≤4), second quartile (4·1–18), third quartile (18·1–60), and fourth quartile (>60); and opium ingestion, first quartile (≤9), second quartile (9·1–30), third quartile (30·1–78), and fourth quartile (>78).