Because of the long lag time before risk of these tumors is reduced among ex-smokers, smoking may affect early stage carcinogenesis. The increase in smoking prevalence during the first two thirds of this century may be reflected in the rising incidence of these tumors in the past few decades among older individuals. The recent decrease in smoking may not yet have had an impact.

Background: Incidence rates have risen rapidly for esophageal adenocarcinoma and moderately for gastric cardia adenocarcinoma, while rates have remained stable for esophageal squamous cell carcinoma and have declined steadily for noncardia gastric adenocarcinoma. We examined anthropometric risk factors in a population-based casecontrol study of esophageal and gastric cancers in Connecticut, New Jersey, and western Washington. Methods: Healthy control subjects (n = 695) and case patients with esophageal squamous cell carcinoma or noncardia gastric adenocarcinoma (n = 589) were frequency-matched to case patients with adenocarcinomas of esophagus or gastric cardia (n = 554) by 5-year age groups, sex, and race (New Jersey only). Classification of cases by tumor site of origin and histology was determined by review of pathology materials and hospital records. Data were collected using in-person structured interviews. Associations with obesity, measured by body mass index (BMI), were estimated by odds ratios (ORs). All ORs were adjusted for geographic location, age, sex, race, cigarette smoking, and proxy response status. Results: The ORs for esophageal adenocarcinoma rose with increasing adult BMI. The magnitude of association with BMI was greater among the younger age groups and among nonsmokers. The ORs for gastric cardia adenocarcinoma rose moderately with increasing BMI. Adult BMI was not associated with risk

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Objective: To identify the molecular basis for prenatally suspected cases of megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) (MIM 249210) in 3 independent families with clinical and radiographic evidence of MMIHS. Methods: Whole-exome sequencing (WES) and Sanger sequencing of the ACTG2 gene. Results: We identified a novel heterozygous de novo missense variant in ACTG2 c.770G>A (p.Arg257His) encoding γ-2 smooth muscle actin (ACTG2) in 2 siblings with MMIHS, suggesting gonadal mosaicism of one of the parents. Two additional de novo missense variants (p.Arg257Cys and p.Arg178His) in ACTG2 were identified in 2 additional MMHIS patients. All of our patients had evidence of fetal megacystis and a normal or slightly increased amniotic fluid volume. Additional findings included bilateral renal hydronephrosis, an enlarged fetal stomach, and transient dilated bowel loops. ACTG2 immunostaining of the intestinal tissue showed an altered muscularis propria, a markedly thinned longitudinal muscle layer, and a reduced amount and abnormal distribution of ACTG2. Conclusion: Our study demonstrates that de novo mutations in ACTG2 are a cause of fetal megacystis in MMIHS and that gonadal mosaicism may be present in a subset of cases. These findings have implications for the counseling of families with a diagnosis of fetal megacystis with a preserved amniotic fluid volume and associated gastrointestinal findings.

Carbonated soft drinks (CSDs) have been associated with gastroesophageal reflux, an established risk factor for esophageal adenocarcinoma. As both CSD consumption and esophageal adenocarcinoma incidence have sharply increased in recent decades, we examined CSD as a risk factor for esophageal and gastric cancers in a U.S. multicenter, population-based case-control study. Associations between CSD intake and risk were estimated by adjusted odds ratios (ORs), comparing the highest versus lowest quartiles of intake. All statistical tests were two-sided. Contrary to the proposed hypothesis, CSD consumption was inversely associated with esophageal adenocarcinoma risk (highest versus lowest quartiles, OR = 0.47, 95% confidence interval = 0.29 to 0.76; Ptrend = .005), due primarily to intake of diet CSD. High CSD consumption did not increase risk of any esophageal or gastric cancer subtype in men or women or when analyses were restricted to nonproxy interviews. These findings indicate that CSD consumption (especially diet CSD) is inversely associated with risk of esophageal adenocarcinoma, and thus it is not likely to have contributed to the rising incidence rates.