Adiposity and risk of oesophageal cancer subtypes in the Million Women Study

Abstract

Background: The strong association of body mass index (BMI) with increased oesophageal adenocarcinoma risk is established, but its relationship with oesophageal squamous cell carcinoma is less clear. There is little evidence regarding the association of abdominal adiposity with either subtype.

Methods: In a large prospective cohort of women in the UK, mean age 56.2 [standard deviation (SD) = 4.9] years, we investigated the risk of oesophageal adenocarcinoma and squamous cell carcinoma in relation to self-reported BMI, waist circumference (WC) and waist-hip ratio (WHR), using Cox regression to estimate adjusted relative risks (RR) and 95% confidence intervals (CIs), taking account of potential reverse causation bias.

Results: During mean follow-up of 17.7 (SD = 4.9) years, 1386 adenocarcinomas and 1799 squamous cell carcinomas of the oesophagus were registered among 1 255 529 women. Compared with women of BMI 22.5 to <25 kg/m2, those with BMI ≥35 kg/m2 had a 2.5-fold risk of adenocarcinoma (adjusted RR = 2.46, 95% CI = 1.99-3.05) and an almost 70% reduction in risk of squamous cell carcinoma (RR = 0.32, 95% CI = 0.22-0.46). These associations were broadly similar in each 5-year follow-up period, and were evident in both never and ever smokers, although somewhat stronger for squamous cell carcinoma among current and past smokers than in never smokers (Pheterogeneity = 0.007). After controlling for BMI, WC and WHR were associated with risk of squamous cell carcinoma but not adenocarcinoma.

Conclusions: In this population of middle-aged women, there was robust evidence that greater BMI is associated with an increased risk of oesophageal adenocarcinoma and a reduced risk of squamous cell carcinoma.

Keywords: Oesophageal cancer; abdominal adiposity; adenocarcinoma; body mass index; squamous cell carcinoma.

Figure 1.

Relative risk of adenocarcinoma and squamous cell carcinoma of the oesophagus by BMI in all women. RR stratified by year of birth and year of recruitment; adjusted for joint smoking and alcohol status, OC use, MHT use, exercise, parity, menopausal status and age, age at menarche, region and socioeconomic status. RR, relative risk; (gs)CI, (group-specific) confidence interval; BMI, body mass index; OC, oral contraceptive; MHT, menopausal hormone therapy

Figure 2.

Relative risk of adenocarcinoma and squamous cell carcinoma of the oesophagus by BMI, in different follow-up periods. RR stratified by year of birth and year of recruitment; adjusted for joint smoking and alcohol status, OC use, MHT use, exercise, parity, menopausal status and age, age at menarche, region and socioeconomic status. RR, relative risk; g(s)CI, (group-specific) confidence interval; BMI, body mass index; OC, oral contraceptive; MHT, menopausal hormone therapy

Figure 3.

Relative risk of adenocarcinoma and squamous cell carcinoma of the oesophagus by BMI, in (a) never, past and current smokers and (b) non-drinkers, and women who drank 1–6 and 7+ drinks per week, excluding the first 5 years of follow-up. RR stratified by year of birth and year of recruitment and adjusted for OC use, MHT use, exercise, parity, menopausal status and age, age at menarche, region and socioeconomic status; results in (a) are additionally adjusted for alcohol intake, and in the case of current smokers for joint number of cigarettes smoked per day and alcohol status; results in (b) are additionally adjusted for smoking status and number of cigarettes smoked in current smokers. RR, relative risk; (gs)CI, (group-specific) confidence interval; BMI, body mass index; OC, oral contraceptive; MHT, menopausal hormone therapy

Figure 4.

Relative risk of adenocarcinoma and squamous cell carcinoma of the oesophagus per 5 kg/m² increase in BMI, in various subgroups, excluding the first 5 years of follow-up. RR stratified by year of birth and year of recruitment; adjusted for (where appropriate) joint smoking and alcohol status, OC use, MHT use, exercise, parity, menopausal status and age, age at menarche, region and socioeconomic status. RR, relative risk; CI, confidence interval; BMI, body mass index; OC, oral contraceptive; MHT, menopausal hormone therapy