The stomach bacterium Helicobacter pylori has a significant role in the development of gastric cancer. Recently, molecular biologists from the University of Zurich identified a mechanism of H pylori that damages the DNA of cells in the gastric mucosa and sets them up for malignant transformation.6 Chronic infection of the gastric mucosa with H pylori is a primary risk factor for developing gastric cancer. The study demonstrated infection of host cells leads to breaks in both strands of the DNA double helix.6
The researchers found the frequency of the double-strand breaks depends on the intensity and duration of the infection. DNA breaks induced by H pylori trigger the cell’s natural DNA damage signaling and repair mechanisms. If the bacterium is eradicated with antibiotics within a few hours of infection, most of the DNA breaks are successfully repaired. Prolonged infections that imitate the conditions of a chronically infected host, however, exhaust the cell’s repair response, and the dangerous double-strand breaks can no longer be repaired, causing genetic mutations or cell death.
New research also suggests alcohol use may play a role in the development of gastric cancers. Heavy beer drinkers who have a specific genetic variant in the cluster of three genes that metabolize alcohol, known as rs1230025, are at significantly greater risk of developing noncardia gastric cancer.7 Heavy beer drinkers who do not have the variant and nondrinkers who have rs1230025 or rs283411 have the same risk; however, it is not as significantly elevated.
“This is a classic gene-environment interaction,” said Eric Duell, PhD, senior epidemiologist in the Cancer Epidemiology Research Program at the Catalan Institute of Oncology in Barcelona, Spain. “Having both of these risks, heavy beer consumption and rs1230025, appears to be worse in terms of gastric cancer risk than having just one or neither.”
Gastric cancer is the second leading cause of cancer death worldwide, but because some countries, including the United States, have much lower rates of gastric cancer than others, Duell believes this disease has a stronger environmental component than a genetic component.8 Alcohol use has been suspected to contribute to gastric cancer, but numerous studies have shown mixed results. Duell and colleagues conducted a comprehensive analysis of alcohol consumption and gastric cancer risk in more than 521,000 people aged 35 to 70 years who participated in the European Prospective Investigation into Cancer and Nutrition (EPIC) study from 1992 through 1998.8
The researchers evaluated the type of alcohol consumed (wine, beer, or liquor) and the location and grade of cancer.8 Total consumption of 60 g of pure ethanol/alcohol from all beverage types combined carried a 65% increased risk. One 12-ounce beer contains about 13 g of pure alcohol/ethanol. However, this association was confined to beer. Duell’s results linked drinking 30 g or more a day of pure ethanol/alcohol as beer to a 75% increased risk of developing gastric cancer. Wine and liquor were not associated with gastric cancer risk.8
In a further analysis, using the EurGast study nested within EPIC, which included 365 gastric cancer cases and 1,284 controls, the researchers analyzed the effects of known single nucleotide polymorphisms (SNPs) in the gene cluster (ADH1) that produces an enzyme that breaks down alcohol.8 Two variants in the ADH1 locus were statistically significantly associated with gastric cancer risk, and only one variant, rs1230025, interacted with beer consumption to increase the risk.
A NEW APPROACH TO EARLY DIAGNOSIS
Diagnosing GI cancers earlier in the course of the disease can dramatically lower morbidity and mortality. New research suggests that a simple urine test may detect cancers of the gut, stomach, and pancreas much sooner. Researchers at the University of Edinburgh, United Kingdom, have identified key proteins in the urine of patients with advanced cancers.9 The findings may help detect these cancers in people who are asymptomatic, and earlier diagnosis may lead to improved survival rates. Currently, only approximately 10% of patients with these cancers, categorized as cancers of the upper GI tract, are still alive 5 years after diagnosis.
The researchers compared urine samples from patients with upper GI cancers with urine samples from people who were cancer-free. Scientists analyzed the samples and identified thousands of proteins. Then, they identified six proteins that were present in 98% of the samples from patients with cancer but absent in almost 90% of the samples from patients without cancer.9
The researchers then narrowed the field down to two proteins, S100A6 and S1009, most likely to appear in samples from patients with cancer but not in samples from people who are cancer-free. The scientists intend to see whether people with early stage cancers, such as those not yet diagnosed, have the same levels of proteins present. They plan to analyze samples from at least 1,000 volunteers and track the participants for a number of years to identify those who develop upper GI cancers.
“The aim of this work is to enable these cancers to be diagnosed much earlier. This would help us to treat the cancer before it has a chance to spread. The majority of these cancers are currently diagnosed late, where no surgery is possible due to its advanced stage. Earlier diagnosis would mean that curative surgery or chemotherapy would be possible for more patients,” said study investigator Holger Husi, MD, of the University of Edinburgh Tissue Injury and Repair Group. ONA
John Schieszer is an international medical journalist and radio broadcaster of The Medical Minute.
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7. Bad mix: heavy beer drinking and a gene variant increases gastric cancer risk. Paper presented at: 102nd Annual Meeting of the American Association for Cancer Research; April 4, 2011; Orlando, Florida.
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9. Husi H, Stephens N, Cronshaw A, et al. Proteomic analysis of urinary upper gastrointestinal cancer markers. Proteomics Clin Appl. 2011;5(5-6):289-299.