Cancer Prevention: Diet, Lifestyle and Beyond
April 20, 2009
DENVER - The American Association for Cancer Research remains committed to cancer prevention. Peter G. Shields, M.D., deputy director of the Lombardi Comprehensive Cancer Center and interim chair of the department of medicine at Georgetown University Medical Center, will host a press conference at the AACR 100th Annual Meeting 2009 that highlights recent breakthroughs.
The press conference will take place at on Monday, April 20 at 11:00 a.m. MST, in room 108 of the Colorado Convention Center. Reporters who cannot attend in person can call into the teleconference using the following information:
U.S./Canada Dial-In: (888) 282-7404
- International Dial-In: (763) 488-9184
- Access Code: 88612909
Shields is a leader in lifestyle prevention measures and his anti-smoking efforts were recently highlighted on NBC's Today Show.
"To effectively prevent cancer, we need a combination of lifestyle and pharmacologic measures. The science highlighted at the Annual Meeting will help us understand how we can best target our efforts toward the most appropriate populations," said Shields.
2116. Colorectal Polyp Type and the Association with Smoking, Charred Meat Intake and mEH
New research on the relationship between diet, lifestyle, genetics and colorectal cancer reinforces broad screening for adenomas, precursor lesions for colorectal cancer. It also provides rationale for further research evaluating the risk of colorectal cancer associated with certain hyperplastic polyps, common polyps traditionally thought to be clinically unimportant.
"Colorectal cancer is the second leading cause of cancer death among men and women, and you can make great strides towards eliminating it with proper screening," said Andrea N. Burnett-Hartman, M.P.H., a doctoral student at Fred Hutchinson Cancer Research Center in Seattle.
Researchers recruited 529 patients with adenoma, 691 patients with hyperplastic polyps, 227 patients with adenomas and hyperplastic polyps, and 772 healthy control patients. These patients were asked a variety of lifestyle questions using a questionnaire and analyses were performed.
Burnett-Hartman and colleagues studied the risk of hyperplastic polyps and adenomas associated with cigarette smoking, charred red meat intake and variations in the mEH gene; a gene responsible for processing some of the carcinogens found in cigarette smoke and charred meat. Although both adenomas and hyperplastic polyps had elevated risks associated with cigarette smoking, the association for hyperplastic polyps was stronger than for adenomas.
If a patient had smoked at least 22 pack-years (one pack-year is equal to smoking one pack per day for one year), the risk of adenomas increased by 68 percent while the risk of hyperplastic polyps increased 2.38-fold. For current smoking status, the risk increase was also 68 percent for adenomas; while the risk of hyperplastic polyps increased 3.02-fold.
Frequency of charred red meat consumption was consistently associated with slightly elevated risks in all polyp groups, but this association was not significant. Also, there was no link between polyps of any type and variation in the mEH gene.
"Colon cancer has a very strong environmental component, but based on the results of our study, these common gene variants do not significantly protect an individual from the carcinogenic effect of smoking," said Burnett-Hartman.
1680. Evidence of Immune Disruption up to 9.8 Years Prior to Diagnosis of Chronic Lymphocytic Leukemia: A Prospective Study
Researchers at the National Cancer Institute may have uncovered a possible early cause of chronic lymphocytic leukemia (CLL), according to a prospective study that involved more than 77,000 patients.
"Although CLL can be a devastating disease, we know little about what causes it, except that it is linked with family history and aging," said Neil Caporaso, M.D., a section chief of the genetic epidemiology branch at the National Cancer Institute.
Drawing on data from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, which included 77,469 healthy individuals, Caporaso and colleagues may have identified an early immune disruption that could lead to CLL.
Caporaso and colleagues identified 109 patients in the database that had a diagnosis of CLL; the diagnosis occurred at a median age of 70 years and 61 percent of the patients were male. These patients had serum available for analysis collected years prior to the diagnosis of CLL. Researchers assessed for the immune measures found in M-proteins and kappa-lambda free light chains.
Researchers assessed the serum tests conducted two to almost ten years prior to diagnosis of CLL. They found that 31 percent of patients who eventually developed CLL had a skewed kappa-lambda free light chain ratio, which Caporaso said is evidence of an early immune disruption. In one patient, this disruption was noted 9.8 years prior to diagnosis. By contrast, hypogammaglobulinemia-an indication of impaired immune function that is common in CLL-was found in only 13.1 percent of patients and was not present in any patients until three years prior to diagnosis.
"It's possible that these disruptions in the kappa-lambda ratio indicate early abnormal clone (collection of similar cells) that lead to CLL," said Caporaso. "Our aim is to better understand them in order to unravel the cause of this puzzling and common blood cancer."
45. The Effect of In Utero and Postnatal Folic Acid Supplementation on Genomic DNA Methylation in the Offspring
Folic acid supplementation provided at all stages of pregnancy and post-pregnancy significantly affected genomic DNA methylation patterns of offspring, according to research conducted at the University of Toronto.
"Early folate nutrition plays an important role in epigenetic programming in the offspring, and this may have an effect on disease risk later in life," said Karen K. Sie, M.Sc., a research scientist at the University of Toronto.
As scientists continue to work to understand the genetic underpinnings of cancer, epigenetics is an emerging science that studies the changes to DNA, including a process called "methylation" where genes are either silenced or activated.
Scientists know that aberrations in DNA methylation patterns play a role in cancer development, but the exact role depends on the tumor type and is still being investigated in many areas.
Sie's study determined that folic acid - the synthetic form of folate, a B-vitamin complex that is a major part of most American diets - plays a role in DNA methylation.
Based on evidence that supplementing folic acid before and during early pregnancy can reduce the risk of neural tube and other congenital defects, all women planning a pregnancy or capable of becoming pregnant are recommended to take 0.4 - 1.0 mg of folic acid for two to three months before conception, throughout pregnancy, and the postpartum period. Furthermore, blood levels and dietary intake of folate have drastically increased in the North American population because of mandatory folic acid fortification implemented in 1998.
Folate plays an important role in DNA methylation and has also been shown to either increase or decrease the risk of several human cancers depending on the time of intervention. However, the effect of maternal folic acid supplementation on DNA methylation in the offspring, and thus the risk of cancers in adulthood, is largely unknown at present.
Sie placed laboratory rats on either a control diet of 2 mg of folic acid supplementation per kg of dietary consumption (equivalent to the recommended dietary allowance for humans - 400 μg/d) or a supplemented diet of 5 mg per kg (equivalent to 1 mg/d). These diets were administered three weeks prior to breeding and remained throughout pregnancy and lactation.
Sie then examined levels of DNA methylation in the offspring of these rats and found that at 14 weeks of age dietary levels of folic acid significantly changed genomic methylation levels in the target organ of interest. Specifically, DNA methylation in the colon and liver at 14 weeks of age was significantly lower among those who had folic acid supplementation.
Sie will present additional data on methylation status at the Annual Meeting.
2115. (COX1) and (COX2) Polymorphisms, NSAID Use, and Colorectal Cancer Risk in the Colon Cancer Family Registry
Since Merck voluntarily recalled Vioxx in 2004, clinicians have been reluctant to use the remaining COX2 inhibitors on the market due to their risk of cardiovascular side effects.
Nevertheless, COX2 inhibitors, and nonsteroidal drugs in general (including ibuprofen and aspirin), have a proven efficacy against developing colorectal cancer, the number two cause of cancer deaths among men and women. Thus, researchers are working to identify patients whose benefit might be high enough to outweigh the risk of cardiovascular disease.
Cornelia Ulrich, Ph.D., a full member of the Cancer Prevention Program in the Public Health Sciences Division at Fred Hutchinson Cancer Research Center, has identified a single nucleotide polymorphism (SNP) that may predict who is at greater risk for colon cancer. SNPs are small genetic changes unique to individuals.
Ulrich and colleagues analyzed data from 2,465 sibling pairs in the Colon Cancer Family Registry and identified 17 COX1 and 13 COX2 tag SNPs.
They found that the presence of COX2 rs4648261 was linked with a reduction in colorectal cancer risk of between 40 to 68 percent. No other SNP was associated with reduced risk. Furthermore, characterizing patients by two SNPs in COX2 suggested that only a subset of patients would derive benefit from NSAID use.
Ulrich said these findings would need to be replicated in larger studies before making clinical recommendations, but this was an important first step.
"Non-steroidal anti-inflammatory drugs have been clearly shown to reduce colorectal cancer risk, but not without their own side effects," said Ulrich. "If we can identify which patients are going to benefit from these drugs, we can more effectively target prevention."
Data will be presented at the press conference by Ulrich's colleague Anna E. Coghill, M.P.H., a graduate research assistant at the Fred Hutchinson Cancer Research Center.
1909. Estimation of Absolute Risk for Prostate Cancer Using SNPS and Family History
A combination of single nucleotide polymorphisms (SNP) and family history may accurately predict who is at risk for prostate cancer and might benefit from chemoprevention with agents such as finasteride, according to research conducted at Wake Forest University School of Medicine.
"This is the first time that we provided a simple tool for estimating absolute risk based on multiple genetic variants in combination. Up until now, we knew that each of these variants carried a slightly increased risk, but in combination the risk prediction is much more reliable," said Jianfeng Xu, M.D., Dr.PH, professor of epidemiology and cancer biology at the Wake Forest University School of Medicine.
Xu and colleagues studied 14 risk alleles on single nucleotide polymorphisms among 2,893 men with prostate cancer and 1,781 men who did not have prostate cancer. Researchers found that the presence of each additional risk allele increased the risk of prostate cancer by about 14 percent. This effect was strongest among men with a family history of prostate cancer.
The strongest risk prediction was observed among men who had at least 15 of the known risk alleles. These men were found to have a 34 percent increased risk of prostate cancer over a period of 20 years; this risk increased to 45 percent if the men also had a family history of prostate cancer.
"Absent this new genetic information, the risk among these men would have only been estimated at 13 percent," said Xu.
Xu said combining this new genetic knowledge with family history will help oncologists make informed decisions regarding a PSA screening regimen. "In addition, these results may motivate preventive measures such as diet/lifestyle intervention and chemoprevention," said Xu.
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The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 28,000 basic, translational and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and nearly 90 other countries. The AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment and patient care. The AACR publishes six major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; Cancer Epidemiology, Biomarkers & Prevention; and Cancer Prevention Research. The AACR also publishes CR, a magazine for cancer survivors and their families, patient advocates, physicians and scientists. CR provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship and advocacy.
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