Precancers 3: All Myeloma Preceded by MGUS

Precancers are the lesions from which cancers develop. Precancers can be easily treated, and when we eliminate precancers, we eliminate the cancers that would have developed from the precancers. This is the message in Precancer: The Beginning and the End of Cancer.

One of the most important questions in precancer research is whether all cancers arise from precancers, or whether some cancers can arise ab initio (from the beginning) as fully malignant clones, without first passing through a precancer phase.

There are many different types of cancer, and most cancers of humans have a putative precancer precursor. Multiple myeloma, and its precursor, MGUS (monoclonal gammopathy of undetermined significance) are discussed in some detail in my recently published book, Precancer: The Beginning and the End of Cancer. Briefly, multiple myeloma is a cancer of plasma cells. Plasma cells are the specialized blood cells that produce gamma globulin antobody molecules. Cancerous plasma cells produce a monoclonal spike of gamma globulins that can be detected by looking at samples of blood. MGUS, the precursor of multiple myeloma, produces a similar monoclonal spike in gamma globulins, but it is not associated with clinically detectable masses of cancer cells.

In a recent paper by Langren et al, the authors answered a simple, fundamental question in tumor biology: Are all cases of myeloma preceded by MGUS?

The paper was published in the journal Blood.

Landgren O, Kyle RA, Pfeiffer RM, et al. Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study. Blood 113:5412-5417, 2009.

The paper is available as an open access document at:

http://bloodjournal.hematologylibrary.org/cgi/content/full/113/22/5412

The authors used data and serum samples from enrollees in the large PLCO (prostate lung colon and ovary) trial currently underway through the National Cancer Institute. They looked specifically at enrollees in the trial who developed multiple myeloma during the trial. All enrollees in the PLCO trial have blood drawn during the multi-year trial. When they looked at prior blood samples for newly diagnosed cases of multiple myeloma, they found MGUS in every instance. Therefore, at least for the 71 examined cases in their study, MGUS always preceded the myeloma.

It is extremely important to have studies (such as this study for multiple myeloma) that indicate that precancer is an obligatory step in carcinogenesis. If only a portion of cancers developed from precancers, we would never be able to eradicate all cancers [by treating their precancers]. On the other hand, if every case of cancer is preceded by a precancer, then we can be certain that if we successfully treat all of the precancers, then no cancers will follow.

-© 2009 Jules J. Berman

tags: precancers, precancer, pre-cancerous condition, precancerous condition, preneoplastic lesions, preneoplasia, ien, intra-epithelial neoplasia, intraepithelial neoplasia, intra-epithelial neoplasm, intraepithelial neoplasm, in situ carcinoma, carcinoma in situ, cis, dcis, din, pin, panin, cin, dysplasia, adenoma, preneoplastic, pre-cancer, pre-cancerous, precancerous, rare disease, orphan disease, orphan drugs, complex disease, disease genetics, genetics of disease, common disease, pathology of disease

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In June, 2014, my book, entitled Rare Diseases and Orphan Drugs: Keys to Understanding and Treating the Common Diseases was published by Elsevier. The book builds the argument that our best chance of curing the common diseases will come from studying and curing the rare diseases.

I urge you to read more about my book. There's a generous preview of the book at the Google Books site.

Precancers: counter-arguments

This blog continues a collection of essays on precancer.

The bulk of funding in the cancer field is directed toward the most frequently occurring, most highly recognizable cancers that are responsible for the greatest number of cancer deaths in the U.S. population (e.g., lung, colon, breast, and prostate cancers). Never mind that mortality from these common cancers has scarcely budged since the War on Cancer began (in the 70s).

Precancers are the lesions that precede the development of cancers. If we developed effective treatments for precancers, we would virtually eradicate cancer. I have been a precancer activist for decades. During that time, I've listened to countless arguments in favor of the status quo (developing treatments for advanced-staged common cancers) and against funding for the precancers.

The arguments against precancer research usually boil down to non-existence arguments (precancers don't even exist), irrelevance arguments (not our job), impracticality arguments (it just isn't practical to treat the precancers), or priority arguments (just about everything else is more important).

I thought it might be useful to lay out all the anti-precancer arguments here, and I can respond to them in future blogs.

Non-existence arguments:

1. There is no such thing as a precancer. The lesions that are called precancers are simply early (or small) cancers.

2. The transition from precancer to cancer is characterized by the acquisition of invasiveness. However, there is no practical way to determine the precise moment that invasiveness is acquired by a lesion. Therefore, there is no practical method to reliably distinguish a precancer from a cancer in every instance (i.e., there is no way to be confident that a lesion has not acquired the ability to invade). Therefore, precancers have no validity as biological entities.

3. There are many genetic and morphological disparities among the different recognized precancers. Since these lesions seem to have no common properties, other than the defining property of "cancer precedence", it hardly seems as though they should be assigned any biological class.

Irrelevance arguments:

4. The mission of the National Cancer Institute, the primary funding agency for cancer research in the U.S. is to develop cures for cancer, not precancer. If precancers were as important as you say they are, there would be a National Precancer Institute. But there isn't.

5. Precancers regress spontaneously. Why should we try to develop treatments for a disease that usually resolves without treatment?

6. Precancer research is just one aspect of cancer prevention, because when the precancer is eliminated, you prevent the cancer. Cancer prevention is an adequately funded area of cancer research, so we really do not need to assign any special funding to precancer research.

Low-priority argument:

7. People are dying from malignant tumors every day. Even if we could prevent cancers, we cannot abandon our responsibility to cancer patients by diverting our limited resources to the precancers.

Impracticality argument:

8. Treating precancers is not feasible for the majority of precancerous lesions that occur in humans. Reducing the incidence of cervical cancer by treating cervical precancer was possible only because the cervix can be inspected and sampled. There is no equivalent method to find and excise the precancerous lesions of pancreas, lung, prostate and breast. Therefore, procedures to detect and treat most precancers are not practical.

Rebuttals follow.

- Copyright (C) 2008 Jules J. Berman

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In June, 2014, my book, entitled Rare Diseases and Orphan Drugs: Keys to Understanding and Treating the Common Diseases was published by Elsevier. The book builds the argument that our best chance of curing the common diseases will come from studying and curing the rare diseases.

I urge you to read more about my book. There's a generous preview of the book at the Google Books site.

tags: common disease, orphan disease, orphan drugs, genetics of disease, disease genetics, rules of disease biology, rare disease, pathology, preneoplasia, premalignant, preneoplastic, incipient neoplasia, pre-cancer, dysplasia, metaplasia, intraepithelial neoplasia, premalignancy, premalignancies, precancers, precancerous, pre-cancer, early cancer, developing cancer, carcinogenesis, cancer development, cancer staging, politics of disease, disease funding, disease geneticfs, cancer genetics, tumor biology