Too many multipotent progenitor stem cells combined with a decline in tumor suppressing myoepithelial cells likely combine to create conditions favorable for cancer to develop.
Mark LaBarge, a cell and molecular biologist in Berkeley Lab’s Life Sciences Division, led a study in which it was determined that aging causes an increase in multipotent progenitors – a type of adult stem cell believed to be at the root of many breast cancers – and a decrease in the myoepithelial cells that line the breast’s milk-producing luminal cells and are believed to serve as tumor suppressors.
This result reminds me of Aubrey de Grey's argument that rejuvenation therapies are the best way to prevent diseases of old age. A key goal for rejuvenation is to get rid of cells that work poorly or which do harm. Another key goal is to increase the supply of cells that do necessary repair and regulatory functions. Achieve both those goals in breasts and the incidence of breast cancer would drop sharply.
“This is a big step towards understanding the cellular basis for age-related vulnerability to breast cancer,” LaBarge says. “Now that we have defined some of the cell and molecular changes that occur in the epithelium during the aging process and we have the ability to assay them functionally, it should be possible to look for ways to avoid those states and perhaps even reverse them.”
Stem cell therapies and other cell therapies aren't just about doing repairs. If we can replace aged stem cells with youthful stem cells we can reduce the risk of cancer. Stem cells collect mutations as they age. Old mutated cells do a poorer job at tissue repair while at the same time accumulation of dangerous combinations of mutations put stem cells closer to the point where they will start dividing uncontrollably.
The use of stem cell therapies to reduce cancer risk looks challenging because the new stem cells have to displace the existing aged stem cells.
An Associated Press article takes a look at smart bomb drugs and other advances reported on in the recent 2012 annual meeting of the American Society of Clinical Oncology (ASCO).
—New “smart” drugs that deliver powerful poisons directly to cancer cells while leaving healthy ones alone.
—A new tool that helps the immune system attack a broad range of cancer types.
The basic problem with cancer is that cancer cells are your own cells. Their similarities to normal cell make them very hard to target without a lot of "friendly fire" deaths of healthy cell. Biotechnological advances (e.g. DNA sequencing) help in part because they allow identification of many more differences between cancer cells and normal cells. What is still an open question: how many unique (or nearly unique) features of cancer cells will be found? How hard to exploit those differences to kill only cancer cells?
All the abstracts for the 2012 annual meeting of (ASCO) are online. Looking thru the category Immunotherapy and Biologic Therapy I count 103 abstracts.
With populations aging and the incidence of cancer soaring pharmaceutical companies are investing more in cancer therapy development. As a result more of the research presented at ASCO has industry involvement. I see this as a good thing because it indicate an acceleration of the rate at which research will get translated into treatments brought to market.
They found that 48% of research accepted for presentation at the meeting in 2011 came from a group where at least one author had a relationship to industry—up from 39% of research presented in 2006. These ties to industry appeared to increase every year.
Interestingly, in a second related abstract by the same authors, Beverly Moy, M.D., M.P.H., clinical director of the Breast Oncology Program and a medical oncologist at the Massachusetts General Hospital, reported that high profile research—selected to be presented more prominently at the meeting—was more likely to come from scientists with relationships to industry. Studies from authors with ties to industry also tended to receive higher scores from their peers.
Industry is going to get more involved in treatments that show the most promise. With advances being made in underlying biotechnologies (e.g. cheap DNA sequencing, microfluidics, gene chips, biotechnologies for growing immune cells) used to identify targets for cancer therapy and for creating treatments the long war against cancer should start producing more victories in the next 20 years.
Have modern sterile environments and antibiotics boosted the rate of cancer? Do we need to work ourselves into a fevered pitch once or twice a year?
There is an inverse relationship between febrile infection and the risk of malignancies. Interferon gamma (IFN-γ) plays an important role in fever induction and its expression increases with incubation at fever-range temperatures. Therefore, the genetic polymorphism of IFN-γ may modify the association of febrile infection with breast cancer risk.
Why? An immune system turned up to kill off invading bacteria might also react more vigorously to attack aberrant cells in your body that have mutated only part of the way toward becoming cancerous. Cells that have mutated all the way into becoming cancerous often have mutations that cause them to excrete substances that suppress the immune system. So vaccines against well developed cancers have fared poorly. But if the immune system could be stimulated into attacking pre-cancerous cells at much earlier stages then in some cases cancer could be prevented.
It might come down to genetic profiles. If you've got the right version of interferon gamma or other immune modulating molecules then a burning fever might keep the doctor away better than apples.
Chinese women who had at least 1 fever per year at a lower rate of breast cancer.
Information on potential breast cancer risk factors, history of fever during the last 10 years, and blood specimens were collected from 839 incident breast cancer cases and 863 age-matched controls between October 2008 and June 2010 in Guangzhou, China. IFN-γ (rs2069705) was genotyped using a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry platform. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated using multivariate logistic regression. We found that women who had experienced ≥1 fever per year had a decreased risk of breast cancer [ORs and 95% CI: 0.77 (0.61–0.99)] compared to those with less than one fever a year.
The effect of the fever appears to be dependent on which genetic variant of interferon gamma the women carried. Interferons play roles in immune regulation. So this comparison of interferon gamma variants was not randomly chosen.
This association only occurred in women with CT/TT genotypes [0.54 (0.37–0.77)] but not in those with the CC genotype [1.09 (0.77–1.55)]. The association of IFN-γ rs2069705 with the risk of breast cancer was not significant among all participants, while the CT/TT genotypes were significantly related to an elevated risk of breast cancer [1.32 (1.03–1.70)] among the women with <1 fever per year and to a reduced risk of breast cancer [0.63 (0.40–0.99)] among women with ≥1 fever per year compared to the CC genotype. A marked interaction between fever frequencies and the IFN-γ genotypes was observed (P for multiplicative and additive interactions were 0.005 and 0.058, respectively).
The idea that lower infectious disease incidence is associated with higher rates of cancer is not new.
Since the 19th century, it has been repeatedly observed that spontaneous cancer regressions were coincided with acute infections and the cancer patients had a remarkable disease-free history before the onset of cancer –. In the 20th century, an inverse association between infectious diseases, particularly febrile ones, and cancer risk has also been consistently found for malignant melanoma and glioma using modern epidemiological methods , , –.
With the widespread introduction of antibiotics and antipyretics since the beginning of the last century, however, the critical role played by fever has often been overlooked, resulting in considerable changes to the clinical course and magnitude of the immune response that develops following acute infections , . These changes may be part of the reasons for the substantial increase in the age-adjusted incidences or mortalities of malignant diseases during the early part of the last century in western countries  and in the late of the last century in China . It has been observed that every 2% reduction in infectious disease mortality was followed by a 2% increase in cancer mortality over a 10-year interval from 1895 to 1963 in Italy .
It would be handy to have a way to periodically turn up the knob on one's immune system to get it to kill pre-cancerous cells. Genetic engineering might eventually help once we figure out what causes some people to have extremely powerful anti-cancer immune systems. See my previous post. Rare People Have Extreme Anti-Cancer Immune Cells.
University of Haifa researchers found evidence that Light At Night (LAN) has harmful health effects. Bright city lights might boost your risks of cancer by suppressing melatonin production.
The results show once again the clear link between LAN and cancer: the cancerous growths in mice exposed to “short days” were smallest (0.85 cubic cm. average), while those mice exposed to the interval of LAN during dark hours had larger growths (1.84 cubic cm. average) and those exposed to “long days” even larger growths (5.92 cubic cm. average).
The study also discovered that suppression of melatonin definitely influences development of the tumor. The size of tumor in mice exposed to “long days” but treated with melatonin was only 0.62 cubic cm. on average, which is not much different from the size of the growth in mice exposed to “short days”. The study also found that the death rate in mice treated with melatonin was significantly lower than in those not treated.
The researchers say that their study results show that suppression of melatonin due to exposure to LAN is linked to the worrying rise in the number of cancer patients over the past few years. However, it is not yet clear what mechanism causes this.
I'm sitting here in a dark room writing this post with only the monitor light to guide me. I've got a Logitech gamer keyboard because it has lighted keys. Very handy.
You might have a bacteria in your stomach that is upping your cancer risk. This isn't new news. But this latest report underscores the risk.
Helicobacter pylori, a bacterium found in about 50% of humans worldwide, can cause stomach ulcers and, in extreme cases, gastric cancer. In an article for F1000 Medicine Reports, Seiji Shiota and Yoshio Yamaoka discuss the possible eradication of H. pylori infections
Infection by the H. pylori bacterium can approach 100% in developing countries. Most infected people do not have symptoms, but many develop problems including stomach ulcers. H. pylori causes more than 90% of all duodenal ulcers and can also contribute to the development of gastric cancer, which is one of the world's biggest medical problems.
Shiota and Yamaoka, from Oita University, Japan, and Baylor College of Medicine, Texas, respectively, report on a large multicenter trial in Japan. Patients with early gastric cancer were randomly treated with H. pylori antibiotics after surgical resection and were followed up for three years. Patients who received antibiotic treatment had a significantly lower risk of developing gastric cancer, confirming the importance of careful management of H. pylori.
Have any readers gotten themselves tested for H. pylori even though you weren't suffering from an ulcer? Did you test positive and then get treated with antibiotics as a cancer preventative?
Couples should probably get tested and treated together to cut the risks of reinfection.
ATLANTA--A new American Cancer Society study finds progress in reducing cancer death rates is evident whether measured against baseline rates in 1970 or in 1990. The study appears in the open access journal PLos ONE, and finds a downturn in cancer death rates since 1990 results mostly from reductions in tobacco use, increased screening allowing early detection of several cancers, and modest to large improvements in treatment for specific cancers.
Temporal trends in death rates are the most reliable measure of progress against cancer, reflecting improvements in prevention, early detection, and treatment. Although age-standardized cancer death rates in the U.S. have been decreasing since the early 1990s, some reports have cited limited improvement in death rates as evidence that the "war on cancer", which was initiated in 1971, has failed. Many of these analyses fail to account for the dominant and dramatic increase in cancer death rates due to tobacco-related cancers in the latter part of the 20th century.
To investigate further, researchers led by American Cancer Society epidemiologist Ahmedin Jemal, Ph.D., used nationwide cancer mortality data for the years 1970 through 2006 from the SEER*Stat database, which defines major cancer sites consistently over time in order to facilitate reporting of long term mortality trends. They found for all cancers combined, death rates (per 100,000) in men increased from 249.3 in 1970 to 279.8 in 1990, and then decreased to 221.1 in 2006, yielding a relative decline of 21% from 1990 (peak year) and a drop of 11% since 1970 (baseline year). Similarly, the death rate from all-cancers combined in women increased from 163.0 in 1970 to 175.3 in 1991, and then decreased to 153.7 in 2006, a relative decline of 12% and 6% from the 1991 (peak year) and 1970 rates, respectively.
You can get a much better picture of the trends by looking at the slideshow graphs associated with the research report. Colorectal cancer has been in decline since 1970. But other cancers didn't start declining until the mid 1990s.
You can read the full text of the report for more details. Death rates declined for a large assortment of cancers including those of the stomach, bladder, brain, kidney, and Non-Hodgkin lymphoma.
During the most recent time period, death rates decreased for cancers of the oral cavity, stomach, bladder, kidney, brain, and Non-Hodgkin lymphoma, and leukemia in both males and females and for cancers of the esophagus and ovary and melanoma and Hodgkin lymphoma in females. In contrast, rates increased for esophagus cancer and melanoma in men, liver cancer in both men and women, and pancreas cancer in women. Death rates stabilized for pancreatic cancer and Hodgkin lymphoma in men and for cervix and corpus and uterus cancers in women. Notably, the 2006 death rates for Hodgkin lymphoma in men, cervical cancer in women, and stomach cancer in both men and women were less than one-third of the 1970 rates.
Many factors contribute to these trends. Early detection, reduced smoking by men, and better treatments all have worked to lower death rates. Hepatitis C, obesity, and a surge in smoking by women all contributed to delaying declines or causing surges in some cancer types.
Most treatments for cancer are still far too crude. Some of the big advances in the next 20 years will come in the form of delivery methods that much more precisely target just the cancer cells with toxins. Also, pieces of regulatory RNA delivered into cells will instruct cancer cells to either die or at least stop dividing.
Doses of radiation from commonly performed computed tomography (CT) scans vary widely, appear higher than generally believed and may contribute to an estimated tens of thousands of future cancer cases, according to two reports in the December 14/28 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.
CT scans have become increasingly common in the United States—about 70 million were performed in 2007, up from 3 million in 1980, according to background information in one of the articles. "While CT scans can provide great medical benefits, there is concern about potential future cancer risks because they involve much higher radiation doses than conventional diagnostic X-rays," the authors of one report write. For example, a chest CT scan exposes the patient to more than 100 times the radiation dose of a routine chest X-ray. "The risks to individuals are likely to be small, but because of the large number of persons exposed annually, even small risks could translate into a considerable number of future cancers."
I've come across marketing literature promoting CT scans as valuable for early detection screening for cancer and other diseases. For the vast majority of the population CT scans for seemingly healthy people seem like an unnecessary risk.
Here are some odds of cancer from CT scans.
The estimated number of CT scans that would lead to the development of one cancer case also varied by type of CT scan and also by each patient's age and sex. For instance, an estimated one in 270 women and one in 600 men who undergo CT coronary angiography (a heart scan) at age 40 will develop cancer as a result. One cancer case will likely occur among every 8,100 women and 11,080 men who had a routine head CT scan at the same age. "For 20-year-old patients, the risks were approximately doubled, and for 60-year-old patients, they were approximately 50 percent lower," the authors write.
When you are older you have fewer years to live due to other reasons. So radiation can zap some cell and kick it on the long road toward cancer and yet you might die from a heart attack or stroke before abnormal cells can accumulate enough additional mutations to become malignant.
Those 70 million CT scans per year in the United States might cause 29,000 future cancers per year. That's a very high number.
"Overall, we estimated that approximately 29,000 future cancers could be related to CT scans performed in the U.S. in 2007," the authors write. This includes an estimated 14,000 cases resulting from scans of the abdomen and pelvis; 4,100 from chest scans; 4,000 from head scans; and 2,700 from CT angiography. One-third of these projected cancer cases would occur following scans performed on individuals age 35 to 54 years, compared with 15 percent due to scans performed in children and teens. Two-thirds of the cancers would be in women.
To put that in perspective, about 1.4 million people get diagnosed with cancer per year in the United States and about 564 thousand die from cancer. So if this estimate about CT scans causing cancer is correct then CT scans are increasing the rate of cancer by slightly more than 2%.
Grand Rapids, Mich. (Aug. 13, 2009) – The number of cancer deaths has declined steadily in the last three decades. Although younger people have experienced the steepest declines, all age groups have shown some improvement, according to a recent report in Cancer Research, a journal of the American Association for Cancer Research.
“Our efforts against cancer, including prevention, early detection and better treatment, have resulted in profound gains, but these gains are often unappreciated by the public due to the way the data are usually reported,” said Eric Kort, M.D., who completed the study while employed as a research scientist at Van Andel Research Institute (VARI) in Grand Rapids, Mich.
Cancer mortality rates are usually reported as composite age-adjusted rates. These rates have been declining modestly since the 1990's. However, these statistics heavily emphasize the experience of the oldest Americans for whom mortality rates are the highest. As a result, trends emerging in younger Americans can be concealed.
The decline in cancer death rates has been sharpest among children.
As an alternative to age-adjustment, Kort examined cancer mortality rates stratified by age and found that for individuals born since 1925, every age group has experienced a decline in cancer mortality. The youngest age groups have experienced the steepest decline at 25.9 percent per decade, but even the oldest groups have experienced a 6.8 percent per decade decline.
We might expect a general decline in cancer death rates due to the decline in the fraction of the population that smokes cigarettes. But that steep decline in child cancer death rates probably isn't due to less exposure to parental cigarette smoke.
We have lots of ways to cut our cancer death risk. Some studies have found a reduced risk of colorectal cancer from aspirin and non-steroidal anti-inflammatory drugs (NSAIDS). Turns out aspirin will help against some colorectal cancers even after diagnosis.
Regular use of aspirin after colorectal cancer diagnosis may reduce the risk of cancer death, report investigators from Massachusetts General Hospital (MGH), Dana-Farber Cancer Institute and Brigham and Women's Hospital. In the August 12 issue of the Journal of the American Medical Association, the study's authors also find that the aspirin-associated survival advantage was seen primarily in patients with tumors expressing the COX-2 enzyme, a characteristic of two-thirds of colorectal cancers.
Intermittent calorie restriction might cut your cancer risk too. Want more ways to cut your cancer risk? Lots of dietary changes will cut your risk of death from cancer.
Results released today from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial show that six years of aggressive, annual screening for prostate cancer led to more diagnoses of prostate tumors but not to fewer deaths from the disease. The study, led by researchers at Washington University School of Medicine in St. Louis and conducted at 10 sites, will appear online March 18 in the New England Journal of Medicine (and in the journal's print edition on March 26).
"The important message is that for men with a life expectancy of seven to 10 years or less, it is probably not necessary to be screened for prostate cancer," says the study's lead author and principal investigator Gerald Andriole, M.D., chief urologic surgeon at the Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital.
Prostate cancer is a slow killer for most men. So this result isn't entirely surprising. Someone getting a diagnosis of prostate cancer when they have 5 years till their heart gives out is probably going to die from heart failure, not prostate cancer. The researchers of this study think that their younger enrollees might eventually show that early detection will help them live longer.
Screening for prostate cancer can reduce deaths by 20%, according to the results of the European Randomized Study of Screening for Prostate Cancer (ERSPC) published online 1700 hours CET, today 18 March (NEJM, Online First*). ERSPC is the world's largest prostate cancer screening study and provides robust, independently audited evidence, for the first time, of the effect of screening on prostate cancer mortality.
The study commenced in the early 1990s involving eight countries – Belgium, Finland, France, Italy, Netherlands, Spain, Sweden and Switzerland - with an overall follow-up of up to 12 years. Participants totalled 182,000 but then narrowed down to 162,000 men in seven countries, aged 55-69; only those who had not been screened could take part. The findings are being unveiled at the 24th Annual Congress of the European Association of Urology (EAU) in Stockholm, Sweden (17 - 21 March 2009).
By initially screening men 55 to 69 years with the PSA marker and offering regular follow up, this led to an increase in early detection. Deaths due to metastasized disease were then reduced. Exact data showed that on average for every 1,408 men screened, 48 had cancer diagnosed and received treatment, resulting in saving one life. Screening took place on average every four years with a mean follow-up over nine years. The cut-off value was a PSA level of 3.0 ng/ml or more. Men with this reading were then offered a biopsy.
What would extend life expectancy much more assuredly: cures for cancer. In the mean time while we wait for cures eat more mushrooms.
Breast cancer rates increased significantly in four Norwegian counties after women there began undergoing mammography every two years, according to a report in the November 24 issue of Archives of Internal Medicine, one of the JAMA/Archives journals. Rates among regularly screened women remained higher than rates among women of the same age who were screened only once after six years, suggesting that some of the cancers detected by mammography may have spontaneously regressed had they not been discovered and treated.
The idea here is that if the women who were tested less often really had as much lasting breast cancer as that found in the more frequently tested group then the former group really should have had more breast cancer cases found when they were finally tested . But they did not show those "missing" breast cancer occurrences at the end of the trial.
Throughout Europe, the start of screening mammography programs has been associated with increased incidence of breast cancer, according to background information in the article. "If all of these newly detected cancers were destined to progress and become clinically evident as women age, a fall in incidence among older women should soon follow," the authors write. "The fact that this decrease is not evident raises the question: What is the natural history of these additional screen-detected cancers?"
Per-Henrik Zahl, M.D., Ph.D., of the Norwegian Institute of Public Health, Oslo, and colleagues examined breast cancer rates among 119,472 women age 50 to 64 who were all invited to participate in three rounds of screening mammograms between 1996 and 2001 as part of the Norwegian Breast Cancer Screening Program. They compared these to rates among a control group of 109,784 women age 50 to 64 in 1992, who would have been invited for screening if the program had existed at that time. Cancers were tracked for six years using a national registry, and at the end of that time all participants were invited to undergo a one-time screening to assess breast cancer prevalence.
As anticipated, breast cancer rates were higher among screened women than among the control group before the final prevalence screening. "Even after prevalence screening in controls, however, the cumulative incidence of invasive breast cancer remained 22 percent higher in the screened group," the authors write. Of every 100,000 screened women, 1,909 had breast cancer during the six-year period, compared with 1,564 of every 100,000 in the control group. Screened women were more likely to have breast cancer at every age.
An alternative explanation is that each test for breast cancer has false negatives and some of these women who are tested less often are having their breast cancer getting missed. Is that possible?
Suppose this finding holds up. It has some obvious implications. First off, some of the reported claimed progress in curing breast cancer might be a mirage. More frequent testing is turning up earlier stage breast cancer. Some of that earlier stage breast cancer might disappear naturally (perhaps via an immune response) if left alone. Treatment might even impair the immune system and leave it less able to defeat the breast cancer on its own.
This report suggests some women are going thru surgery, chemo, and radiation who would otherwise recover from breast cancer without ever knowing they even had it. Given the ravages of the treatments this is quite unfortunate. But perhaps scientists can discover characteristics of cancers or of patient immune systems that make regression more likely. Then those conditions could be induced in women with breast cancer in order to cause more regressions.
We can expect great advances in early detection. Microfluidic devices will test blood samples with great sensitivity and detect blood markers for cancer (and other diseases as well). The tests will become so sensitive that we are going to hit a problem: we have lots of very small cancers in our bodies (really) that are stuck at the stage of being unable to grow more blood vessels. These very small cancers are going to contribute to a sort of background noise of cancer signals. I expect as the blood assay tests become more sensitive to very low concentrations of cancer markers we will even find that as we age a gradual slow rise in cancer blood markers will be found.
On the bright side, the ability to detect very early stage cancer will lend itself to immune treatments against cancer. Caught early enough a cancer won't have as many mutations that protect it from an immune response. In particular, I'm hopeful that vaccines and monoclonal antibodies will be developed that will rid of cancers without our even having to know the exact location of each cancer. Perhaps as we age we will periodically go in for an anti-cancer immunotherapy that basically kills any early stage cancer cells that have grown up since a previous treatment.