To the Editor: Esophageal and junctional adenocarcinoma has a 7-to-1 male predominance.1 The main risk factors are obesity and gastroesophageal reflux, which are equally distributed between the sexes.2–4 However, a predominantly abdominal fat distribution (the type more typical for men) is a stronger risk factor than body mass index (BMI).5–8 Abdominal adiposity might facilitate reflux through increased intra-abdominal pressure and has therefore been suggested as an explanation for the male predominance of esophageal adenocarcinoma. If so, the male-to-female sex ratio among cases would be low or absent among lean patients and high among the overweight. We tested this hypothesis using data from a population-based nationwide Swedish case-control study, which has been described in detail elsewhere.3 In brief, participants were enrolled in 1995–1997. Cases were recruited from all 195 Swedish hospital departments treating these patients. Tumor classification was comprehensive and uniform. Controls were randomly selected and frequency matched by age and sex of the cases. Because of the matching on sex, controls were used to estimate person-years by using data from the Swedish Register of the Total Population. At personal interviews, information on BMI was assessed as: (1) 20 years before interview, (2) 20 years of age, (3) maximum adult BMI, and (4) minimum adult BMI. Incidence rate ratio was used to estimate relative risk (RR). Person-years were calculated by age (<60, 60–69, or 70–79 years), sex, and BMI (<22, 22 to <25, or ≥25) derived from the Swedish population. The BMI distribution in controls was used to estimate person-years in the population. Poisson regression was used to calculate RR and 95% confidence intervals (CIs), where log-transformed person-years were included in the model as an offset. To evaluate effect modification of BMI on the association between sex and esophageal adenocarcinoma, we included age, sex, BMI, and an interaction term between sex and BMI in the model. Likelihood ratio χ2 statistics was used to obtain P value for test of effect modification. The study included 451 cases (85% participation) and 820 controls (73%). The male-to-female ratio was 7-to-1. Half of the cases were overweight (BMI ≥ 25) 20 years before interview. There was no increased RR with increasing levels of BMI in any of the BMI assessments (Table). Regarding BMI 20 years before interview, the male predominance in overweight participants (RR 5.8, 95% CI 3.9–8.8) was not higher than in lean (RR 7.4, 3.9–14.1). The corresponding RRs at 20 years of age were the same (RR 7.2, 3.6–14.3 and RR 7.2, 4.8–10.6, respectively). Regarding minimum BMI, there was instead a higher male predominance in lean participants and for maximum BMI the male predominance was at least as strong in lean (Table).TABLE: Age-adjusted RR and 95% CI of Esophageal or Gastroesophageal Junctional Adenocarcinoma for Males Relative to Females by Category of BMIThese results provide no support for the hypothesis that an increased male predominance of esophageal adenocarcinoma correlates with higher BMI. The population-based design with high participation rates and the possibility to estimate person-years from population-based controls were prerequisites for the study. Registry of all Swedish residents enabled assessment of person-years at risk from which the cases were derived, and thus made it possible to adjust for age. Other advantages include the thorough tumor classification, personal interviews, and assessment of BMI at different time points. Among weaknesses is the low incidence of esophageal adenocarcinoma in women, which reduced statistical power. There was possible misclassification of BMI, but any such bias should be similar between cases and controls. Although abdominal adiposity is clearly overrepresented in men and there is a strong male predominance of esophageal adenocarcinoma, we found no evidence of an increased age-adjusted male predominance with higher levels of BMI. This argues against abdominal obesity as a factor in explaining the excess male risk. Katarina Lagergren Fredrik Mattsson Upper Gastrointestinal Research Department of Molecular Medicine and Surgery Karolinska Institutet Stockholm, Sweden Jesper Lagergren Upper Gastrointestinal Research Department of Molecular Medicine and Surgery Karolinska Institutet Stockholm, Sweden Division of Cancer Studies King’s College London London, United Kingdom [email protected]