Table 4.

Quantitative dose-response relationships between alcohol consumption and causally impacted disease conditions

Disease	Monotonic relationship	Threshold	Dose-response relationship RR (95% confidence interval)	Differential effect mortality vs. morbidity	RR for ex-drinker compared to lifetime abstainers
Tuberculosis	Not enough data to model dose-response relationship	Yes, modelled at 40g/day or diagnosis of alcoholism	After exclusion of small studies because of suspected publication bias from Lönnroth et al., 2008: 2.94 (1.89-4.59). [34]	Hypothesized [241] but not modelled	Not computed; CRA will use all-cause mortality RRs
Mouth, nasopharynx, other pharynx and oropharynx cancer	Yes	No	From Corrao et al. (2004) (based on 14 case-control & 1 cohort studies): 25 g/day: 1.86 (1.76–1.96); 50 g/day: 3.11 (2.85–3.39); 100 g/day: 6.45 (5.76–7.24). [68]	No data from any of the meta-analyses	Not computed; CRA will use all-cause mortality RRs
Oesophagus cancer	Yes	No	From Corrao et al. (2004) (based on 13 case-control & 1 cohort studies): 25 g/day: 1.39 (1.36–1.42); 50 g/day: 1.93 (1.85–2.00); 100 g/day: 3.59 (3.34–3.87). [68]	No data from any of the meta-analyses	Not computed; CRA will use all-cause mortality RRs
Colon and rectum cancer	Yes	No	From Corrao et al. (2004) colon: (based on 12 case-control & 4 cohort studies): 25 g/day: 1.05 (1.01–1.09); 50 g/day: 1.10 (1.03–1.18); 100 g/day: 1.21 (1.05–1.39); rectum: (based on 4 case-control & 2 cohort): 25 g/day: 1.09 (1.08–1.12); 50 g/day: 1.19 (1.14–1.24); 100 g/day: 1.42 (1.30–1.55). [68]	No data from any of the meta-analyses	Not computed; CRA will use all-cause mortality RRs
Liver cancer	Yes	No	From Corrao et al. (2004) (based on 8 case-control & 2 cohort studies): 25 g/day: 1.19 (1.12–1.27); 50 g/day: 1.40 (1.25–1.56); 100 g/day: 1.81 (1.50–2.19). [68]	No data from any of the meta-analyses	Not computed; CRA will use all-cause mortality RRs
Larynx cancer	Yes	No	From Corrao et al. (2004) (based on 20 case-control studies): 25 g/day: 1.43 (1.38–1.48); 50 g/day: 2.02 (1.89–2.16); 100 g/day: 3.86 (3.42 – 4.35). [68]	No data from any of the meta-analyses	Not computed; CRA will use all-cause mortality RRs
Breast cancer (female)	Yes	No	From Hamajima et al. (2002) (58 515 women with invasive breast cancer and 95 067 controls from 53 studies): 35–44 g/day: 1.32 (1.19 – 1.45); ≥45 g/day: 1.46 (1.33 – 1.61) as compared with abstainers. The RR of breast cancer increased by 7.1% (5.5–8.7%) for each additional 10 g/day intake of alcohol, i.e. for each extra unit or drink of alcohol consumed on a daily basis. [71]	No data from any of the meta-analyses	Not computed; CRA will use all-cause mortality RRs
Diabetes mellitus	No	No	From Baliunas et al. (2009):	No data to establish comparison (almost all risk relations between alcohol consumption and diabetes were based on morbidity)	Men:1.18 (0.89-1.52); Women: 1.14 (0.99-1.31)
			Men: nadir at 22 g/day: 0.87 (0.76-1.00); deleterious > 60 g/day: 1.01 (0.71-1.44);
			Women: nadir at 24 g/day: 0.60 (0.52-0.69); deleterious at>50 g/day: 1.02 (0.83-1.26). [277]
Epilepsy	Yes	No	From Samokhvalov et al. (in press): not enough data to model separate by sex: 25g/day: 1.37 (1.28-1.47); 50 g/day: 1.86 (1.62-2.13); 100 g/day: 3.44 (2.61-4.52). [97]	Not enough data to model	Not enough data to estimate. CRA will use all-cause mortality RRs.
Hypertensive disease	Men: yes, women: no	No	From Taylor et al., (2009):	Insufficient data for mortality, so the relationship was only modelled for hypertension morbidly	Both gender: 0.94 (0.49-1.39)
			Men: 25g/day: 1.25 (1.19-1.32); 50g/day: 1.62 (1.46-1.81); 100g/day: 2.64 (2.14-3.26).
			Women: <5 g/day: 0.82 (0.73-0.93); 25 g/day: 1.24 (0.87-1.77); 50g/day: 1.81 (1.13-2.90), 100g/day: 2.81 (1.56-5.05). [278]
Ischaemic heart disease	No	No	From Corrao et al. (2000): curvilinear relationship for average consumption; based on all 54 studies: nadir at 25 g/day: 0.75 (0.73-0.77); protective effect up to 90 g/day: 0.94 (0.90-1.00); harmful effect at 113 g/day: 1.08 (1.00-1.16); based on 28 high quality cohort studies: nadir at 20 g/day: 0.80 (0.78-0.83); protective effect up to 72 g/day: 0.96 (0.92-1.00); detrimental effect >89 g/day: 1.05 (1.00-1.11). [108]	Yes, stronger relationship with mortality	Men mortality: 1.21 (1.12-1.30); morbidity: 0.98 (0.89 -1.08) Women mortality 1.39 (1.17-1.66); morbidity 1.11 (0.94-1.32).
			Bagnardi et al. (2008) estimated an RR for irregular heavy drinking patterns compared to abstainers of 1.10 (1.03-1.17). [118]
			From Roerecke & Rehm (submitted): Heavy drinking occasions (>60g per occasion) compared to non-heavy drinking occasions: 1.45 (1.24-1.70). [279]
Ischaemic stroke	No	No	From Reynolds et al. (2003): <12 g/day: 0.80 (0.67-0.96); 12-24 g/day: 0.72 (0.57-0.91); 24-60 g/day: 0.96 (0.79-1.18); >60 g/day: 1.69 (1.34-2.15). [155]	Men: no, women: yes	Strokes combined: men 1.33 (0.91-1.96); women 1.15 (0.71-1.92); both 1.22 (0.87-1.76)
Haemorrhagic and other non-ischaemic stroke	Men: yes, women: no (only for morbidity)	No	From Reynolds et al. (2003): <12 g/day: 0.79 (0.60-1.05); 12-24 g/day: 0.98 (0.77-1.25); 24-60 g/day: 1.19 (0.80-1.79); >60 g/day: 2.18 (1.48-3.20). [155]	Men: no, women: yes
Conduction disorders and other dysrhythmias	Yes	Not clear; volumes of average consumption < 36g have RR of about 1, but based on few studies	From own meta-analysis (not enough data to model separate by sex): <24 g/day: 1.02 (0.94-1.12); 24-36 g/day: 1.13 (0.98-1.30); 36-48 g/day: 1.19 (1.03-1.37); 48+ g/day: 1.45 (1.24-1.69).	Not enough data to model	Not enough data to estimate.
Lower respiratory infections: pneumonia	Yes	Not clear, as lower volumes of average consumption have RR of about 1; mechanism similar to TB	From own meta-analyses (not enough data to model separate by sex: 25g/day: 1.13 (1.03-1.24); 50 g/day: 1.27 (1.05-1.53); 100 g/day: 1.61 (1.10-2.35)	Not enough data to model	Not enough data to estimate.
Cirrhosis of the liver	Yes	There are good indications for a threshold for morbidity as endpoint, but not for mortality [170]	From Rehm et al., (in press): mortality	Yes, higher risks for mortality [170]	Morbidity and mortality combined: Women: 6.50 (2.21-19.08); Men: 1.31 (0.67-2.57); Women only based on one study [280]
			Men: 30g/day: 2.8 (2.3-3.4); 54g/day: 7.0 (5.8-8.0); >60 g/day: 14.0 (11.7-16.7);
			Women: 30g/day: 7.7 (6.3-9.5); 54g/day: 14.7 (11.0-19.6); >60 g/day: 22.7 (17.3-30.1); Morbidity
			Men: 30g/day: 0.7 (0.5-1.0); 54g/day: 2.3 (1.7-3.2); >60 g/day: 5.0 (3.9-6.4);
			Women: 30g/day: 2.4 (1.8-3.2); 54g/day: 5.9 (3.7-9.3); 60g/day: 6.1 (4.6-8.0).
			From categorical analysis [170]
Pancreatitis	Yes, but risk for lower doses of average volume of drinking may not be significantly different from risk of abstention	Yes, a threshold effect at about 48 g/day or 4 drinks average volume was found [171]	From Irving et al. (2009): not enough data to model separately by sex:; 25g/day: 1.10 (1.08-1.12); 50g/day: 1.46 (1.34-1.59); 100g/day: 4.50(3.22-6.31). [171]	Not enough data to model	Not enough data to estimate. CRA will use all-cause mortality RRs.
Preterm birth complications	Yes	No	From Rehm et al. (2004):	Not relevant	Not meaningful, as only drinking during pregnancy can affect newborns
			Men <40 g/day: 1.00; 40-60 g/day: 1.40; 60+g/day: 1.40; Women <20 g/day: 1.00; 20-40 g/day: 1.40; 40+ g/day: 1.40. [9]
Injury	Yes	No	From Corrao et al. (1999): 25 g/day: 1.4 (1.2–1.6); 50 g/day: 2.0 (1.5-2.6); 100 g/day: 4.0 (2.4-6.6)	Yes, higher risks for mortality	Not meaningful, as risk is mainly determined by drinking before injury
			Corrao et al. (1999) was based on average volume in g/day. [222]

Abbreviations: CRA - Comparative Risk Assessment; RR – relative risk