Contribution of H-pylori and Smoking Trends to US Incidence of Intestinal-Type Noncardia Gastric Adenocarcinoma: A Microsimulation Model

Harvard Pilgrim Health Care, Куинси, Massachusetts, United States
PLoS Medicine (Impact Factor: 14.43). 05/2013; 10(5):e1001451. DOI: 10.1371/journal.pmed.1001451
Source: PubMed


Although gastric cancer has declined dramatically in the US, the disease remains the second leading cause of cancer mortality worldwide. A better understanding of reasons for the decline can provide important insights into effective preventive strategies. We sought to estimate the contribution of risk factor trends on past and future intestinal-type noncardia gastric adenocarcinoma (NCGA) incidence.
We developed a population-based microsimulation model of intestinal-type NCGA and calibrated it to US epidemiologic data on precancerous lesions and cancer. The model explicitly incorporated the impact of Helicobacter pylori and smoking on disease natural history, for which birth cohort-specific trends were derived from the National Health and Nutrition Examination Survey (NHANES) and National Health Interview Survey (NHIS). Between 1978 and 2008, the model estimated that intestinal-type NCGA incidence declined 60% from 11.0 to 4.4 per 100,000 men, <3% discrepancy from national statistics. H. pylori and smoking trends combined accounted for 47% (range = 30%-58%) of the observed decline. With no tobacco control, incidence would have declined only 56%, suggesting that lower smoking initiation and higher cessation rates observed after the 1960s accelerated the relative decline in cancer incidence by 7% (range = 0%-21%). With continued risk factor trends, incidence is projected to decline an additional 47% between 2008 and 2040, the majority of which will be attributable to H. pylori and smoking (81%; range = 61%-100%). Limitations include assuming all other risk factors influenced gastric carcinogenesis as one factor and restricting the analysis to men.
Trends in modifiable risk factors explain a significant proportion of the decline of intestinal-type NCGA incidence in the US, and are projected to continue. Although past tobacco control efforts have hastened the decline, full benefits will take decades to be realized, and further discouragement of smoking and reduction of H. pylori should be priorities for gastric cancer control efforts. Please see later in the article for the Editors' Summary.

1 Follower
16 Reads
  • Source
    • "GC is one of the most common malignancies in developing countries, where it ranks second in terms of incidence rate and third in terms of mortality rate among the male population, and ranks fourth in terms of both incidence rate and mortality rate among the female population, according to the most recent global statistics [1,2]. GC is also the third leading cause of cancer mortality in China [3], where over 70% of GC has already become clinically advanced by the time of surgical exploration, thus surgical resection alone is no longer curative [4]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: This work aimed to synthesize a cathepsin B (CTSB)-cleavable tumor-targeting prodrug peptide doxorubicin (PDOX) and study the in vivo efficacy and toxicities on an animal model of gastric peritoneal carcinomatosis (PC). PDOX was synthesized using doxorubicin (DOX) attaching to a CTSB-cleavable dipeptide Ac-Phe-Lys and a para-amino-benzyloxycarbonyl (PABC) spacer. PC model was established by injecting VX2 tumor cells into the gastric sub-mucosa of 40 rabbits, which then were randomized into 4 groups: the Control (n = 10) without treatment, the HIPEC (n = 10) receiving cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC), the PDOX (n = 10) and the DOX (n = 10) receiving systemic chemotherapy with PDOX 50.0 mg/kg or DOX 5.0 mg/kg, respectively, after CRS + HIPEC. The median overall survivals (OS) were 23.0 d (95% CI: 19.9 d - 26.1 d) in the Control, 41.0 d (36.9 d - 45.1 d) in the HIPEC, 65.0 d (44.1 d - 71.9 d) in the PDOX, and 58.0 d (39.6 d - 54.4 d) in the DOX. Compared with the Control, the OS was extended by 70% in the HIPEC (p < 0.001) and further extended by 40% in the DOX (p = 0.029) and by 58% in the PDOX (p = 0.021), and the PC severity was decreased in the HIPEC and further decreased in the PDOX and DOX. Animals receiving DOX treatment showed hematological toxicities with marked reduction of white blood cells and platelets, as well as cardiac toxicities with significant increases in creatine kinase mb isoenzyme, evident myocardium coagulation necrosis, significant nuclear degeneration, peri-nucleus mitochondria deletion, mitochondria-pyknosis, and abnormal intercalated discs. But these toxicities were not evident in the PDOX. PDOX is a newly synthesized tumor-targeting prodrug of DOX. Compared with DOX, PDOX has similar efficacy but reduced hematological and cardiac toxicities in treating rabbit model of gastric PC.
    Molecular Cancer 03/2014; 13(1):44. DOI:10.1186/1476-4598-13-44 · 4.26 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Smoking is a well-established risk factor for atherosclerotic disease, but its role as an independent risk factor for venous thromboembolism (VTE) remains controversial. We conducted a meta-analysis to summarize all published prospective studies and case-control studies to update the risk for VTE in smokers and determine whether a dose-response relationship exists. We performed a literature search using MEDLINE (source PubMed, January 1, 1966 to June 15, 2013) and EMBASE (January 1, 1980 to June 15, 2013) with no restrictions. Pooled effect estimates were obtained by using random-effects meta-analysis. Thirty-two observational studies involving 3,966,184 participants and 35,151 VTE events were identified. Compared with never smokers, the overall combined relative risks (RRs) for developing VTE were 1.17 (95% CI 1.09-1.25) for ever smokers, 1.23 (95% CI 1.14-1.33) for current smokers, and 1.10 (95% CI 1.03-1.17) for former smokers, respectively. The risk increased by 10.2% (95% CI 8.6%-11.8%) for every additional ten cigarettes per day smoked or by 6.1% (95% CI 3.8%-8.5%) for every additional ten pack-years. Analysis of 13 studies adjusted for body mass index (BMI) yielded a relatively higher RR (1.30; 95% CI 1.24-1.37) for current smokers. The population attributable fractions of VTE were 8.7% (95% CI 4.8%-12.3%) for ever smoking, 5.8% (95% CI 3.6%-8.2%) for current smoking, and 2.7% (95% CI 0.8%-4.5%) for former smoking. Smoking was associated with an absolute risk increase of 24.3 (95% CI 15.4-26.7) cases per 100,000 person-years. Cigarette smoking is associated with a slightly increased risk for VTE. BMI appears to be a confounding factor in the risk estimates. The relationship between VTE and smoking has clinical relevance with respect to individual screening, risk factor modification, and the primary and secondary prevention of VTE. Please see later in the article for the Editors' Summary.
    PLoS Medicine 09/2013; 10(9):e1001515. DOI:10.1371/journal.pmed.1001515 · 14.43 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Helicobacter pylori has been causally linked to a number of diseases, including peptic ulcer disease, gastric adenocarcinoma, mucosa-associated lymphoid tissue lymphoma, and dyspepsia. It is the most prevalent bacterial pathogen in humans, and while the overall prevalence in the United States is about 30 %, the distribution is heterogeneous amongst different ethnic groups. Recent immigrants from high prevalence areas such as Korea, Japan, and China bear an increased burden of its disease and complications. There is clear evidence that treatment of H. pylori resolves peptic ulcer disease, and increasing evidence for protection against development of gastric adenocarcinoma. However, H. pylori treatment failure is common and alternative regimens may be necessary. The following case-based review will highlight these issues, including the epidemiology of H. pylori in the immigrant population, an approach to dyspepsia, and the role of H. pylori in gastric adenocarcinoma.
    Journal of General Internal Medicine 09/2013; 29(3). DOI:10.1007/s11606-013-2630-y · 3.42 Impact Factor
Show more

Preview (2 Sources)

16 Reads
Available from