Rising lymphoma rates

anjou

Well-known member
LLymphoma Rate Rise Continues to Baffle Researchers
J Natl Cancer Inst -- Ken Garber 93 (7): 194 4apr01
Back in 1991, the National Cancer Institute sponsored a 2-day workshop to ponder the mysterious "emerging epidemic" of non-Hodgkin's lymphoma. A decade later. the mystery persists, and NHL cases continue to rise. "It's been quite dramatic," says pathologist Dennis Weisenburger, M.D.. of the I University of Nebraska. "Something is clearly going on, and we don't understand it."

Since 1950, NHL has increased in frequency by about 4% a year. Overall, between 1973 and 1997, incidence grew 81%. This year 56,200 Americans will be diagnosed with NHL., which is now the fifth most common non-skin cancer in the United States. "It is remarkable how NHL has ;none from being what we would consider a rare disease ... to what we consider in the moderate risk, midrange of cancers." said Sheila Zahm, Sc.D., deputy director of the NCI's Division of Cancer Epidemiology and Genetics. "It's really a phenomenal increase compared to most other cancers."

And while the growth rate has leveled off somewhat in recent years, NHL remains among the deadliest cancers. Five-year survival rates have remained stuck around 51% since 1980. For largely incurable low-grade forms of lymphoma, there has been no real statistical improvement for 3 decades.

Causal Chain'?
Something goes wrong in the immune system to cause NHL, but the causal chain remains unknown. Tumors consist of abnormal, malignant lymphoid cells--either T cells or, more commonly, B cells---originating in the body's lymphatic system. Exactly how genetic and environmental factors interact to turn lymphocytes into cancer cells continues to baffle researchers.

On the genetic level, some things are known. Chromosomal translocations area hallmark of NHL. In follicular lymphoma, for example. gene exchange between chromosomes 14 and 18 takes place, leading to the overexpression of the BCL-2 gene on 18, preventing programmed cell death (apoptosis). This allows the B cell to survive to sustain other genetic damage that eventually makes it cancerous. The breakpoint on 14 is at an immunoglobulin (lg) gene locus, so something apparently goes wrong during lg rearrangement in the bone marrow to cause the translocation. Similar translocations, usually involving oncogenes and antigen receptor loci. take place in other lymphomas.

That sets the stage for inevitable genetic errors. "B cells are sort of built to recombine DNA," noted Dan Longo, M.D., scientific director of the National Institute on Aging. "The follicular center [where B cells are selected for antigen response] is a mutation factors." But why repair fails to take place. and, more generally, which genetic and environmental factors predispose certain individuals to the genetic errors that cause NHL, remain unknown. "We don't know which [susceptibility] genes are mutated, unlike the clean work in colon cancer," said Longo.

Risk Factors?
And no clear risk factors have emerged for NHL in the general population. But severe immunosuppression often leads directly to NHL. Up to 25°o of patients with one of the rare inherited immunodeficiencies will develop B-cell lymphomas during their lifetimes. Organ transplant patients. who receive immunosuppressive drugs, are at high risk. as are bone marrow transplant patients. Patients who receive chemotherapy or radiation for other cancers often develop NHL years later.

Most strikingly, AIDS patients run a 100- to 300-fold higher risk for NHL than the general population. (AIDS, though, accounts for a minor part of the overall rise in incidence.) Epstein-Barr virus (EBV), a ubiquitous herpesvirus that can immortalize B cells, activates in many immunosuppressed patients. leading to NHL. Reduced immune surveillance against abnormal cells, or compensatory proliferation of lymphocytes (making mistakes more likely), probably accounts for other AIDS-related cases.

But are viruses the culprit in the general population? EBV also leads to Burkitt's lymphoma (common in Africa), and human T cell IN lymphotrophic virus-1 is closely associated with adult T-cell lymphoma, widespread in Japan but rare in the United States. But the vast majority of non-AIDS cases in western countries appear to have nothing to do with viruses. "There have been conscientious efforts made to find the footprints of viruses in lymphomas." said Longo. "It seems unlikely that a major fraction of common lymphomas will be explainable by viral activity."

Yet no other risk factor has emerged to explain the surge in NHL cases. Studies have linked NHL to hair dyes, nitrate in drinking water. dietary fat and red meat. autoimmune diseases and especially to occupational exposure to herbicides, pesticides, and organic solvents. But. except tier the herbicide/pesticide connection, the links are tenuous at best. And high chemical exposure on farms cannot account for NM, in the general population.

"Something has changed in the world to lead to the huge, huge increase in lymphoma in the general population," said Patricia Hartge, Sc.D.. deputy director of tire NCI's Epidemiology and Statistics Program. "1'm pretty mystified."

The best lead so far is immune system depression and stimulation. "There could be agents in the environment that are causing some sort of subtle immune deficiency." said Weisenburger. "[And] when you expose the whole population to it you see an increase in cancers that's fairly significant." Similarly, if the immune system is under constant challenge, B-cell and T-cell activity jump, and the likelihood of mutation rises. "The body is desperately trying to make up for the tact that it's under attack," explained Zahm.

AIDS. involving both immune suppression and immune challenge, offers a possible-though extreme-model. "Could it be that a very similar thing is going on, but at a very low level, in the population'?" asked Weisenburger. "That's a possibility. But it's very hard to prove."

That's because low-potency risk factors barely register in epidemiologic studies, if at all. Yet if almost everyone is exposed, such factors could account for the lymphoma epidemic. "Some subtle immune deficiency in conjunction with increased exposure to environmental antigens. or viruses. or other things could increase that risk from, say, zero to maybe twofold," said Weisenburger. "You would double the number of cases" -roughly what's happened with NHL over the last 30 years.

But this theory may he simplistic. A large case-control study in San Francisco recently showed a protective effect associated with allergies, marijuana use. and multiple sexual partners. "A small amount of immune system stimulation may be good," concluded principal investigator Elizabeth Holly, Ph.D., of the University of California at San Francisco.

The NCI is nova completing a large. case-control epidemiologic study aimed at testing the immune depression arid stimulation idea. Specifically. the study is looking at the incidence of NHL among people who are exposed to chemicals at a lower level than farmers because of pesticide use in lawns, gardens. and homes, schools, and other buildings and the presence of pesticides in food, Zahm said. The study will also examine common medical conditions and procedures that could have a subtle effect on the immune system. Meanwhile. Holly's group is embarking on a major new study focusing mainly on diet, autoimmune diseases. and prior medical history. She hopes the two groups can pool their results.

So far, a decade alter the NCI first addressed the NHL epidemic, few answers have emerged. Weisenburger, for one, does not expect a breakthrough anytime soon. Teasing out NHL's subtle risk factors "probably requires either very large epidemiologic [studies], or some special tools we don't have," he said. "We haven't figured out how to look for risk factors in new ways. And so we're continuing to apply the old methods. and I'm not sure that's going to work."
 

bjr229

New member
Interesting stuff. I wonder if these researchers ever thought of looking at airplanes as the factor? Commercial air flights became affordable and common starting in the 70's. Could it be that this allowed viruses to hitchhike around the world as people travelled? This would greatly increase the number of viruses we would be exposed to, and also give the virus more chances to mutate.

When you read about people who live in the remote parts of Alaska and Canada, they are surprisingly healthy. It appears that they don't get exposed to much since no one travels in the winter.

My two cents worth.

Brian
 

Kiersten

New member
I am reminded of the greatest sci-fi show EVER, Star Trek, where the dudes land on an unexplored planet and civilization had apparantly disappeared. And they usually found some cause for disease. And a few of the dudes would catch the disease. But Bones would always have the antidote at the last minute.

Makes me think what our last minute will be like. Will we have a last minute? The "cure" for my cancer could give me another cancer. The "cure" for my e-m-i-l has given her two DIFFERENT cancers, and this time WILL take her life.

There's little way around the pollution and chemicals and "cures", so what can we really do?
 

Mary Kay

New member
Anjou,
I can see the high incidence of NHL in my life, that has to be more then just the fact that I am more aware of NHL. In my small office of 14 people. I have NHL, two new employees have someone in their family with NHL (one person's 14 year old son has NHL, and one person's mother has NHL) In my small country neighborhood, one male neighbor has died of NHL, and my husband's old boss's daughter has NHL. The wife of a man he works with now has NHL. Now that is scary, that in the past 3 years, so many people just in my life alone all have NHL
frown.gif
 

myrnabob

New member
Re: Rising lymphoma rates--from Polio vaccine?

From http://www.eurekalert.org/pub_releases/2002-03/bcom-sfi030702.php :

SV40 found in human lymphoma samples
HOUSTON-- (March 9, 2002) -- Evidence of simian virus 40 (SV40) infection found in 42 percent of non-Hodgkin lymphoma samples could shed new light on the genesis of these blood cancers that have become more common over the past 30 years, said Baylor College of Medicine scientists in a report in the March 9 issue of The Lancet, a British scientific journal. About 55,000 new cases of the disease are diagnosed annually.
"This is an important finding because cancers with a viral cause offer the possibility of developing new and better ways of treating and diagnosing and ultimately preventing the tumor," said Dr. Janet Butel, chairman of the department of molecular virology and microbiology at Baylor and senior author of the report.

"This study further demonstrates that humans can be infected by SV40, an infection that was not suspected in the past," she said. SV40 usually infects rhesus monkeys. However, in the 1950s and early 1960s, some batches of polio vaccine became accidentally infected with the virus. The vaccine was then given to millions of people worldwide. Because some patients with SV40-positive tumors were born after 1963 and would not have been exposed to the contaminated vaccine, it appears that SV40 continues to spread among humans in ways that are not yet clear. Recently, evidence of SV40 infection has also been found in human brain tumors, tumors of the lining of the chest and abdomen (mesothelioma), and osteosarcomas.

In their study, Butel and Dr. Regis Vilchez, an assistant professor of medicine and first author on the report in The Lancet, analyzed samples from 154 patients who had lymphomas and found 42 percent positive for SV40 DNA, whereas many control samples were negative.

Dr. Adi Gazdar, a colleague at the University of Texas Southwestern Medical School in Dallas, performed a similar study that confirmed the presence of SV40 in samples of non-Hodgkin lymphomas. His study also appears in the March 9 issue of The Lancet.
 

Renee46

New member
I am fairly new to this site and it has been VERY helpful to me and I have also meet many friends. I just finished in September 6 cycles of CHOP + Rituxan for Marginal B Cell Lymphoma, Stage IV. Then I was told I have Hep C, Hep C is another cause of B-Cell Lymphoma. I will be starting treatment for the Hep C in a few months, my GI said if we can Cure the Hep C (gentoype 2b, high success of cure) then we will never have to worry about the Lymphoma again. If there are any Heppers out there and you want to chat you can email me at rwsalamon@aol.com
 
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