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A number of hypotheses have been advanced to explain the rapid increase of the incidence of esophageal adenocarcinoma in the US. A major problem in identifying and understanding the nature of this increase is the difficulty in untangling age effects from temporal trends due to cohort and period effects. To address this problem, we have developed multi-stage carcinogenesis models that describe the age-specific incidence of adenocarcinoma of the esophagus and of the gastric cardia with separate adjustments for temporal trends. These models explicitly incorporate important features of the cancers, such as the metaplastic conversion of normal esophagus to Barrett's esophagus (BE). We fit these models separately to the incidence of adenocarcinoma of the esophagus and of the gastric cardia reported in the Surveillance Epidemiology and End Results (SEER) registry over the period 1973-2000. We conclude that the incidence of both cancers is consistent with a sequence that posits a tissue conversion step in the target organ followed by a multi-stage process with three rate-limiting events, the first two leading to an initiated cell that can expand clonally into a premalignant lesion, and the third converting an initiated cell into a malignant cell. Temporal trends in the incidence of both cancers are dominated by dramatically increasing period effects.
A number of hypotheses have been advanced to explain the rapid increase of the incidence of esophageal adenocarcinoma in the US. A major problem in identifying and understanding the nature of this increase is the difficulty in untangling age effects from temporal trends due to cohort and period effects. To address this problem, we have developed multi-stage carcinogenesis models that describe the age-specific incidence of adenocarcinoma of the esophagus and of the gastric cardia with separate adjustments for temporal trends. These models explicitly incorporate important features of the cancers, such as the metaplastic conversion of normal esophagus to Barrett's esophagus (BE). We fit these models separately to the incidence of adenocarcinoma of the esophagus and of the gastric cardia reported in the Surveillance Epidemiology and End Results (SEER) registry over the period 1973-2000. We conclude that the incidence of both cancers is consistent with a sequence that posits a tissue conversion step in the target organ followed by a multi-stage process with three rate-limiting events, the first two leading to an initiated cell that can expand clonally into a premalignant lesion, and the third converting an initiated cell into a malignant cell. Temporal trends in the incidence of both cancers are dominated by dramatically increasing period effects.
Persons diagnosed with Barrett’s esophagus (BE) are at increased risk of developing esophageal adenocarcinoma (EA). Obesity is a major risk factor for both BE and EA. The purpose of this study was to determine the extent to which the adipokines leptin and adiponectin, both of which are deregulated in obese states, mediate the obesity-BE relationship. In this case-control study based in western Washington State, 106 male and 71 female patients newly diagnosed with BE were compared with 112 male and 64 female controls from the general population. Relationships between leptin and adiponectin, obesity, and BE were examined using unconditional logistic regression. Females in the highest tertiles of body mass index and waist circumference were at the greatest risk of BE (adjusted OR=4.3 (95% CI=1.7–10.7), Ptrend= <.01; OR=4.9 (95% CI=1. 9–12.5), Ptrend= <.01, respectively) compared to females in the lowest tertiles. Adjustment for leptin and adiponectin attenuated these associations by 43% and 41%, respectively. Similarly, males in the highest tertiles of waist circumference and waist-to-hip ratio were at the greatest risk of BE (adjusted OR=2.1 (95% CI=1.1–4.2), Ptrend=.08; OR=2.7 (95% CI=1.3–5.7), Ptrend=.01, respectively) compared to males in the lowest tertiles. However, adjustment for leptin and adiponectin attenuated these associations by only 6% and 8%, respectively. Our study results are consistent with the notion that circulating leptin and adiponectin partially mediate the obesity-BE relationship, particularly in women. Leptin and adiponectin’s role in the progression from normal epithelium to BE and on to EA should be further elucidated.
The term “cancer precursor” refers to specific morphologic changes that precede the development of cancer. Knowledge of the etiology of cancer precursors varies considerably by anatomic site. In part, this might reflect the relative inaccessibility of a site to tissue sampling (e.g., ovary and pancreas) and hence the difficulty of detecting and diagnosing precursors at that site. This chapter describes some of the more well studied sites, for which there is substantial knowledge of the histopathology, epidemiology, and natural history.
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