Alcohol consumption and cancer incidence in women: interaction with smoking, body mass index and menopausal hormone therapy

Abstract

Background: Alcohol consumption has been associated with increased risks of certain site-specific cancers and decreased risks of some other cancers. There is, however, little reliable evidence as to whether the alcohol-associated risks for specific cancers are modified by smoking, body mass index (BMI) and menopausal hormone therapy (MHT) use.

Methods: In the prospective UK Million Women Study, 1,233,177 postmenopausal women without prior cancer, mean age 56 (SD 5) years, reported their alcohol consumption in median year 1998 (IQR 1998-1999), and were followed by record-linkage for incident cancer. 438,056 women who drank no alcohol or < 1 drink/week were excluded. Cox regression yielded adjusted relative risks (RRs) and 95% confidence intervals (CIs) for 21 cancers by alcohol amount; statistical significance of interactions with smoking, BMI and MHT use was assessed after allowing for multiple testing.

Results: In 795,121 participants, mean consumption was 6.7 (SD 6.4) alcoholic drinks/week. During 17 (SD 5) years of follow-up, 140,203 incident cancers were recorded. There was strong evidence for a substantial association between alcohol intake and risk of upper aero-digestive cancers (oesophageal squamous cell carcinoma, oral cavity, pharynx and larynx; RR per 1 drink/day = 1.38 [95% CI 1.31-1.46]). There was also strong evidence for more moderate positive associations with breast, colorectal and pancreatic cancer (RRs per 1 drink/day = 1.12 [1.10-1.14], 1.10 [1.07-1.13], 1.08 [1.02-1.13] respectively), and moderate negative associations with thyroid cancer, non-Hodgkin's lymphoma, renal cell carcinoma and multiple myeloma (RRs per 1 drink/day = 0.79 [0.70-0.89], 0.91 [0.86-0.95], 0.88 [0.83-0.94], 0.90 [0.84-0.97] respectively). Significant interactions between alcohol and smoking were seen for upper aero-digestive cancers (RRs per 1 drink/day = 1.66 [1.54-1.79], 1.23 [1.11-1.36], 1.12 [1.01-1.25] in current, past, and never smokers respectively). BMI and MHT did not significantly modify any alcohol-associated risks.

Conclusions: These findings provide robust evidence that greater alcohol intake, even within relatively moderate ranges, increases the risk of cancers of the aerodigestive tract, breast, colorectal and pancreatic cancer, and probably decreases the risk of thyroid cancer, non-Hodgkin's lymphoma, renal cell carcinoma and multiple myeloma. Associations of alcohol intake with cancer risk were not modified by MHT use, adiposity or smoking, except in the case of upper aero-digestive cancers, where the alcohol-associated risk was largely confined to smokers.

Keywords: Alcohol; Cancer; Epidemiology.

Fig. 1

Relative risk by cancer site per 1 drink/day increase in alcohol intake * Relative risk and 95% confidence intervals (CI) per 1 drink/day increase in alcohol intake, adjusted for region, body mass index, deprivation index, educational attainment, smoking, strenuous exercise, use of oral contraceptives and menopausal hormones and stratified by year of birth and year completed recruitment questionnaire. For estimation of trends, intake categories 1-2, 3-6, 7-14, 15+ drinks/week were scored according to the mean alcohol intake at reassessment 7.8 years later (2.6, 5.5, 10.0, 17.0 drinks/week respectively). † See methods for histological classification. †† Additional adjustment for age at menarche, age at first birth, parity and family history of breast cancer. § Additional adjustment for age at menarche, age at first birth and parity. Includes only women who answered no to hysterectomy at recruitment. ¶ Additional adjustment for age at menarche, age at first birth and parity. Includes only women who answered no to bilateral oopherectomy at recruitment

Fig. 2

Relative risk by cancer site per 1 drink/day increase in alcohol intake by smoking status * Relative risk and 95% confidence intervals (CI) per 1 drink/day increase in alcohol intake, adjusted by region, body mass index, deprivation index, educational attainment, smoking (and number of cigarettes/day in current smokers), strenuous exercise, use of oral contraceptives and menopausal hormones and stratified by year of birth and year completed recruitment questionnaire. For estimation of trends, intake categories 1-2, 3-6, 7-14, 15+ drinks/week were scored according to the mean alcohol intake at reassessment 7.8 years later (2.6, 5.5, 10.0, 17.0 drinks/week respectively). ** denotes statistically significant at the FDR threshold (0.05). † See methods for histological classification. †† Additional adjustment for age at menarche, age at first birth, parity and family history of breast cancer. § Additional adjustment for age at menarche, age at first birth and parity. Includes only women who answered no to hysterectomy at recruitment. ¶ Additional adjustment for age at menarche, age at first birth and parity. Includes only women who answered no to bilateral oophorectomy at recruitment

Fig. 3

Relative risk of upper aerodigestive cancers by alcohol intake and smoking status * Relative risk and 95% g-s confidence intervals (CI) by amount of alcohol consumed and smoking compared to consumption of 1-2 drinks/week in never smokers (relative risk=1.0), adjusted for region, body mass index, deprivation index, educational attainment, strenuous exercise, use of oral contraceptives and menopausal hormones and stratified by year of birth and year completed recruitment questionnaire. The relative risks are for categories of one to two, three to six, seven-14, ≥ 15 drinks/week at recruitment plotted against the remeasured averages 7.8 years later in each of these categories (never smokers 2.5, 5.3, 9.6, 16.3 drinks/week respectively; past smokers 2.9, 5.8, 10.4, 17.2 drinks/week respectively; current smokers < 10 cigarettes/day 3.0, 6.0, 10.6, 17.6 drinks/week respectively; current smokers ≥ 10 cigarettes/day 2.7, 5.8, 10.6, 17.9 respectively). † Includes oesophageal squamous cell carcinoma, oral cavity and pharynx and larynx cancers

Fig. 4

Relative risk by cancer site per 1 drink/day increase in alcohol intake by body mass index * Relative risk and 95% confidence intervals (CI) per 1 drink/day increase in alcohol intake, adjusted by region, deprivation index, educational attainment, smoking (and number of cigarettes/day in current smokers), strenuous exercise, use of oral contraceptives and menopausal hormones and stratified by year of birth and year completed recruitment questionnaire. For estimation of trends, intake categories 1-2, 3-6, 7-14, 15+ drinks/week were scored according to the mean alcohol intake at reassessment 7.8 years later (2.6, 5.5, 10.0, 17.0 drinks/week respectively). ** denotes statistically significant at the FDR threshold (0.05). † See methods for histological classification. †† Additional adjustment for age at menarche, age at first birth, parity and family history of breast cancer. § Additional adjustment for age at menarche, age at first birth and parity. Includes only women who answered no to hysterectomy at recruitment. ¶ Additional adjustment for age at menarche, age at first birth and parity. Includes only women who answered no to bilateral oophorectomy at recruitment

Fig. 5

Relative risk by cancer site per 1 drink/day increase in alcohol intake by MHT use * Relative risk and 95% confidence intervals (CI) per 1 drink/day increase in alcohol intake, adjusted by region, body mass index, deprivation index, educational attainment, smoking (and number of cigarettes/day in current smokers), strenuous exercise and use of oral contraceptives and stratified by year of birth and year completed recruitment questionnaire. For estimation of trends, intake categories 1-2, 3-6, 7-14, 15+ drinks/week were scored according to the mean alcohol intake at reassessment 7.8 years later (2.6, 5.5, 10.0, 17.0 drinks/week respectively). ** denotes statistically significant at the FDR threshold (0.05). † See methods for histological classification. †† Additional adjustment for age at menarche, age at first birth, parity and family history of breast cancer. § Additional adjustment for age at menarche, age at first birth and parity. Includes only women who answered no to hysterectomy at recruitment. ¶ Additional adjustment for age at menarche, age at first birth and parity. Includes only women who answered no to bilateral oophorectomy at recruitment