Obesity Outweighs Reflux Disease as Esophageal Cancer Risk

BRISBANE, Australia, Oct. 11 -- Obesity even without reflux disease is associated with six times the risk of developing esophageal adenocarcinoma compared with those of normal weight, researchers here found.

For those with gastroesophageal reflux disease (GERD) without obesity, the esophageal adenocarcinoma risk was five times greater than for those without GERD, they added.

But obesity combined with GERD was associated with a 16 times greater risk of esophageal adenocarcinoma, David C. Whiteman, MBBS, Ph.D., of the Queensland Institute of Medical Research here, and colleagues, reported online in Gut.

Men and those younger than 50 were especially vulnerable to esophageal adenocarcinoma, they reported.

Rates of esophageal adenocarcinoma have been rising rapidly, the authors wrote, and epidemiological studies strongly implicate GERD as the primary causal factor.

However, obesity has been linked to other cancers and thus "there are plausible grounds for speculating that high levels of body fat may promote carcinogenesis through other pathways," Dr. Whiteman and his colleagues said.

The researchers undertook a population-based case-control study to measure the relative risks of adenocarcinoma of the esophagus and the gastro-esophageal (GE) junction associated with obesity alone, and its interactions with age, sex, GERD, and smoking.

Of almost 800 patients, 367 had adenocarcinomas of the esophagus and 426 had cancer at the GE junction. They were compared with 1,580 controls randomly sampled from a population register for Australia. Patients (ages 18 to 79) were diagnosed from July 2001 through June 2005.

The risks of esophageal adenocarcinoma increased monotonically with body mass index (BMI) (P for the trend 0.001). Highest risks were seen for BMI greater than 40 kg/m² (odds ratio (OR) = 6.1, 95% CI 2.7 to 13.6) compared with a ''healthy'' BMI of 18.5 to 24.9 kg/ m².

Adjustment for GERD and other factors modestly attenuated these risks, the researchers reported.

Risks associated with obesity were substantially higher among men (OR = 2.6, CI 1.8 to 3.9) than women (OR = 1.4, CI 0.5 to 3.5), and among those younger than 50 (OR = 7.5, CI 1.7 to 33.0) than those older than 50 (OR = 2.2, CI 1.5 to 3.1).

Obese patients with frequent symptoms of GERD had significantly higher risks (OR = 16.5, 95% CI 8.9 to 30.6) than people with any level of obesity but no reflux (OR = 2.2, CI 1.1 to 4.3) or reflux but no obesity (OR = 5.6, 2.8 to11.3). This was consistent with a synergistic interaction between these factors, the researchers said

There were similar associations, but of smaller magnitude, for GE junction adenocarcinomas.

These findings held even after taking into account other factors known to be implicated in the disease, such as smoking. High-level smokers had significantly higher risks of esophageal and GE junction cancer than never-smokers.

After reclassifying participants according to BMI and smoking history, the researchers found that the risks increased with BMI among never-smokers. However, there was no evidence that obesity and heavy smoking together led to higher or lower risks than predicted under an additive model, they said

The study's limitations were dealt with in various ways, the researchers explained. They noted, for example, that the lack of a reliable measure of past infection with H. pylori, which has been implicated in suppressing appetite and body weight, may have confounded the association between BMI and the cancer.

Recall bias was another study limitation mentioned, and the less-than-ideal participation rates may have led to selection bias, they said.