New studies on cancer prevention presented at 101st AACR Annual Meeting 2010

Interest in cancer prevention is increasing as scientists continue to learn new information and confirm what was already suspected.

"At least half of all cancer deaths are preventable by what we already know about healthy eating, exercise, maintaining appropriate weight, avoiding smoking and going for regular screenings," said Ernest T. Hawk, M.D., M.P.H., vice president of the division of cancer prevention & population sciences at The University of Texas M. D. Anderson Cancer Center.

Hawk will host a press conference at the American Association for Cancer Research 101st Annual Meeting 2010 on Tuesday, April 20 at 8:30 a.m. ET in room 142 of the Walter E. Washington Convention Center. Reporters who cannot attend in person, can call in using the following information:

U.S. and Canada: (888) 282-7404
International: (706) 679-5207
Access Code: 59334057

Hawk said the studies presented at this press conference "are helping us to take prevention to the next level. We are developing ways to make our strategies more specific, more tailored and more personal."

The following abstracts will be presented during this press conference:

883. Weight gain is associated with an increased risk of prostate cancer recurrence in the PSA era
Embargo: 2:00 p.m. ET, April 18, 2010

Obesity and weight gain contribute to risk of prostate cancer recurrence after prostatectomy, especially in inactive men, according to results of a retrospective cohort study.

Corinne E. Joshu, M.P.H., Ph.D., a postdoctoral fellow in the department of epidemiology at Johns Hopkins Bloomberg School of Public Health in Baltimore and colleagues followed 1,337 men with clinically-localized prostate cancer who underwent prostatectomy between 1993 and 2006. Participants completed a survey on dietary, lifestyle and medical factors (i.e. weight, height, physical activity and sedentary behavior) five years before surgery and one year after.

By the end of follow-up in 2008, 102 men had prostate cancer recurrence. Men whose cancer had recurred were older, more likely to have poorer pathological tumor characteristics and were less likely to have a family history of prostate cancer than men whose cancer did not recur.

"Weight gain of at least five pounds five years before surgery, to one year after surgery was associated with a nearly two-fold increased of prostate cancer recurrence compared with men who maintained their weight," said Joshu.

At five years prior to prostatectomy, 54 percent of the men were overweight and 9 percent were obese; among men who gained at least five pounds, the average weight gain was about 10 pounds by one year after surgery, according to Joshu. Obesity after surgery was associated with about a 1.7-fold increased risk.

"Our message is consistent with public health messages that are given for chronic conditions and other types of cancer: it is best for men to avoid weight gain or obesity, especially as they age — including men with prostate cancer," said Joshu.

2825. Red meat and heterocyclic amine intake, metabolic pathway genes and bladder cancer risk
Embargo: 2:00 p.m. ET, April 19, 2010

High consumption of red meat or fried meat and a person's genetic makeup are all associated with an increased risk of developing bladder cancer.

"The most interesting finding was that the magnitude of the meat-cancer association depends on a person's genetic background," said first author of the study Jie Lin, Ph.D., assistant professor in the department of epidemiology at the University of Texas M. D. Anderson Cancer Center, Houston.

Using data collected in a large Texas bladder cancer case-control study, Lin and colleagues analyzed the association between meat consumption, cooking methods, genetic predisposition and bladder cancer risk. The study included 884 patients with confirmed bladder cancer and 878 controls. Epidemiologic and dietary data, including meat intake and meat cooking methods, were collected using standard food frequency questionnaires.

Higher consumption of beef steaks, pork chops and bacon were each associated with increased bladder cancer risk, according to Lin. But these results were not limited to just red meat; fried chicken and fried fish conferred an increased bladder cancer risk when consumed in high amounts.

When evaluating the effect of cooking method, Lin and colleagues found meats cooked at the medium-done and well-done level were associated with a 1.46-fold and 1.94-fold increased risk, respectively, when compared to the rare-done level. Lin explained that high temperature-cooking methods generate heterocyclic amines, which are carcinogenic compounds that increase cancer risk.

"Reducing red meat consumption and/or avoiding eating meats cooked at very high temperature, like those pan-fried, grilled or barbecued, may reduce one's risk for developing bladder cancer," said Lin.

Results also indicated that some participants were genetically predisposed to cancer risk; those who carried a high number of unfavorable genotypes in the pathway had a more significant risk of developing bladder cancer. This suggests that red meat intake and genetic variants in the metabolic pathways influence bladder cancer susceptibility.

"Cancer is caused by multiple risk factors — such as environmental exposure, diet and genetic background — and their interactions," Lin said. "The current results highlight the importance of studying gene-diet interactions in cancer risk assessment and have valuable implications in bladder cancer prevention."

901. Prediagnostic body mass index (BMI), plasma C-peptide levels and cigarette smoking predict prostate cancer-specific and overall mortality: A 27-year survival analysis in men with prostate cancer
Embargo: 2:00 p.m. ET, April 18, 2010

Although obesity and smoking are not necessarily risk factors for prostate cancer, they do appear to increase the risk of dying from the cancer once a patient is diagnosed with it, according to a study conducted at the Brigham and Women's Hospital.

"In addition, obesity and smoking are major causes of death in the general population. Because prostate cancer risk increases with age, only a fraction of prostate cancer patients die of the disease. The majority of the patients with localized and low Gleason grade disease die of other causes such as cardiovascular diseases. We, therefore, need to take overweight/obesity and smoking history into account when evaluating clinical prognosis once they are diagnosed," said Jing Ma, M.D., Ph.D., associate professor of medicine at the Brigham and Women's Hospital.

Ma and colleagues extracted prediagnostic body mass index (BMI) and smoking data from the Physicians Health Study, which included 2,715 men diagnosed with prostate cancer between 1982 and 2009.

During the 27 years of follow-up, 882 of these men died, 11 percent of which was due to prostate cancer.

Researchers performed standard statistical analysis to determine the risk factors for mortality and found that for each five point increase in BMI, risk of mortality increased 52 percent. Compared to those who had never smoked, current smokers had a 55 percent increase in mortality from prostate cancer.

1816. Attributable risks for hepatocellular carcinoma in the United States
Embargo: 9:00 a.m. ET, April 19, 2010

Controlling diabetes may lead to decreased risk of hepatocellular carcinoma (HCC), or liver cancer, in the United States.

"In our study, more cases of HCC were attributable to diabetes than to any of the other risk factors we examined," said Katherine A. McGlynn, Ph.D., M.P.H., senior investigator at the National Cancer Institute Division of Cancer Epidemiology and Genetics. "On a population level, the prevention of diabetes in the United States would have a greater effect on decreasing the rate of HCC than would the prevention of alcohol-related conditions or chronic hepatitis C virus (HCV) infection."

In addition to diabetes, alcohol-related disorders and HCV, the researchers examined the risks attributable to chronic hepatitis B virus (HBV) infection, obesity and several rare metabolic disorders. McGlynn and colleagues at the NCI and at Baylor College of Medicine, Houston, investigated these individual risk factors and their association with HCC, and stratified the results based on race/ethnicity and gender.

They analyzed data from the SEER-Medicare linked database. The case population consisted of 5,607 people diagnosed with HCC with at least three pre-diagnostic years of Medicare coverage between 1994 and 2005; the control population was a 5 percent random sample of people residing in SEER-Medicare locations.

Overall, approximately 63 percent of HCC was associated with one or more risk factors mentioned above — a relationship that was highest among Asians (67.9 percent) and lowest among blacks (53.5 percent).

Diabetes was associated with the greatest percentage of cases (33.5 percent), followed by alcohol-related disorders (23.9 percent), HCV infection (20.7 percent), HBV infection (5.7 percent), rare metabolic disorders (3.1 percent) and obesity (2.7 percent), according to McGlynn.

These risk-factor-related percentages varied individually by racial/ethnic group and gender.

"This research suggests that it would be worthwhile to target HCC prevention strategies at persons with diabetes, in addition to persons with other risk factors such as alcohol-related conditions, HCV and HBV infection," McGlynn said.

The researchers are currently expanding on these results by conducting follow-up studies to determine whether the risk of HCC among people with diabetes is affected by their diabetes medications. Ultimately, however, McGlynn and colleagues hope to determine the unidentified risk factors linked to the 37 percent of HCC cases not explainable by the risk factors above.

4699. Environmental tobacco smoke in relation to bladder cancer risk: The Shanghai Bladder Cancer Study

Exposure to environmental tobacco smoke, also called secondhand smoke, increased the risk of bladder cancer among participants of a population-based study conducted in Shanghai, China.

Specifically, lifelong nonsmokers whose mothers smoked more than 10 pack-years had a 3.51-fold increased risk of bladder cancer compared to lifelong nonsmokers who had never been exposed to secondhand smoke. A pack-year is defined as 20 cigarettes smoked every day for one year.

A similar, albeit weak association with bladder cancer risk was observed for those who were exposed to secondhand smoke from other family members living in the same household. People working in an office shared with coworkers who smoked cigarettes five or more hours a day also were at two-fold increased risk of bladder cancer.

"This is the first time there has been a clear demonstration of the effect of secondhand smoke on bladder cancer risk," said Li Tao, M.D., lead author and a research fellow at the Masonic Cancer Center, University of Minnesota.

Previous studies, mostly epidemiological ones, failed to establish a strong association due to inadequate measures of secondhand tobacco exposure and small number of subjects involved. By contrast, Tao's study included more than 200 bladder cancer patients and an equal number of healthy participants who never used tobacco products.

In-person interviews were conducted using a structured questionnaire to ask participants for the smoking history of their mothers, fathers and other family members during subjects' childhood at home. Besides domestic settings where spouses and other family members smoked cigarettes, the questionnaire asked participants about the smoking habits of coworkers at their workplace. This thorough and comprehensive ascertainment for exposure to secondhand smoke made this study unique and stood out from previous studies.

Furthermore, some genetically determined enzymes such as cytochrome P450 1A2 (CYP1A2) and N-acetyltransferase 2 (NAT2), which catalyze the metabolism of potential bladder carcinogens present in tobacco smoke, were measured on all participants. These laboratory measurements provided further clues to the link of the secondhand smoke to bladder cancer.

Overall, those who were exposed to secondhand smoke had a 20 percent to 30 percent increased risk of bladder cancer, but this was what statisticians call a non-significant finding, suggesting it could have resulted by chance.
However, when researchers considered only participants who had an elevated CYP1A2 enzyme activity (which activates more tobacco bladder carcinogens) and a low NAT2 enzyme activity (which slows the detoxification of tobacco bladder carcinogens), secondhand smoke was associated with more than two-fold increased risk of bladder cancer, which was statistically significant.

These findings suggest that the genetic traits may contribute to the overall risk of bladder cancer for a given individual who is exposed to secondhand smoke.

"Given the complexity in genetically determined metabolism of tobacco bladder carcinogens, this genetic analysis will need to be further explored," Tao said.

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