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

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)¼4.9] 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 (SD¼4.9) 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 BMI35 kg/m2 had a 2.5-fold risk of
adenocarcinoma (adjusted RR¼2.46, 95% CI¼1.99–3.05) and an almost 70% reduction in risk of squamous cell carcinoma (RR¼0.32,
95% CI¼0.22–0.46). 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 (Pheterogeneity¼0.007). 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.