The preposterous notion put forth by the title of this editorial is nevertheless surprisingly evident today related to the several growth and differentiation factors currently used in dentistry and medicine. My first experience with this notion came about in the late 1980s when one of my cancer patients was debilitated and dying from runaway squamous cell carcinoma. What began as a poorly differentiated squamous cell carcinoma of the buccal mucosa was now a smelly fungating mass eroded through the skin of his face and neck. The horrific appearance of this man and the knowledge that we treated many osteoradionecrosis patients with hyperbaric oxygen prompted an otorhinolaryngologist (ENT) cancer surgeon to berate me for creating such a mess and that the hyperbaric oxygen obviously fed and caused this cancer to proliferate into this grotesque end point. After at least 5 to 8 minutes of a venomous verbal assault, I calmly informed him that this patient never received hyperbaric oxygen. My ENT colleague stormed off muttering the illogical retort that hyperbaric oxygen would have done the same thing. This was followed by the patient's sympathetic wife who proceeded to inform me that her husband's cancer started to get out of control after his last hair cut and asked if stimulating hair growth by cutting it could have begun the cancer regrowth.
Whereas I can forgive a layperson for leaping to a conclusion, I cannot forgive a Board Certified Cancer Surgeon for the same thing. Simply, cancers are a population of cells that have a mutant genome that began by inherited or acquired mistakes in cell division or by some mutagen (carcinogen). The cancer cell population itself mutates at a much faster rate than normal cells, and left untreated or resistant to treatment, this cell population obeys the laws of natural selection. That is, the most aggressively proliferating cell line and/or the one that secretes its own tumor directed growth factors every minute of everyday takes over the population as it did in this patient unrelated to the oxygen in hyperbaric oxygen or to the atmospheric oxygen he breathed.
Today, dental practitioners practicing dental implantology frequently use such growth factors such as rhPDGF-bb (Gem-21), platelet-rich plasma, plasma rich in growth factors, recombinant human Bone Morphogenetic Protein-2/ACS (rhBMP-2/ACS [INFUSE]). Similarly, physicians are frequently using some of these as well and also rhpTH-34 (Forteo), Salmon Calcitonin (Miacalcin), etc. Each one has been recently accused of causing cancer as much as hyperbaric oxygen was feared to do but never did in the 1980's.
There are several reasons why these growth and differentiation factors cannot, do not, and have not epidemiologically been shown to cause cancers. The first is that they never enter a cell or the cell nucleus. They only work on the external cell membrane surface receptors, which exert their effects through normal gene expressions with feedback controls. Even if used on a cell with a mutant genome or an established cancer, it is only a one-time application with short life duration as contrasted to a cancer that secretes a battery of autocrine growth factors for self-promotion every minute. Second, growth and differentiation factors are not mutagens. It takes a mutagen (eg, cigarette tars, human papilloma virus, radiation, etc.) to start a cancer. Third, and most importantly, is the track record. None of the aforementioned commercially available growth factors has created an epidemic of cancer across many hundreds of thousands of users and none have been shown to be associated with a statistically higher incidence of cancer in any controlled study. Probably, the best example of this is the epidemiological data concerning rhBMP-2/ACS (Infuse), which is the latest growth and differentiation factor to come under a non–evidenced-based assault. That is, in randomized studies comparing Infuse-grafted patients to matched patients grafted without Infuse, the cancer rate was not statistically different at 1.2% versus 1.9%.1 Additionally, such background rates for cancer in aged-matched nongrafted patients is 1.8%2 underscoring that the track record as the final judge of cancer causation does not support the also biologically unsound assertion that these growth and differentiation factors place our patient at greater risk for cancer development. To suggest that these growth and differentiating factors cause cancers is a confusion between coincidence and causality as exampled by the high incidence of haircuts associated with cancer development. Therefore, practitioners can feel assured that if they get a haircut on the way to their office, breath air (20% oxygen) on the way, and then use one of these growth and differentiating factors to gain a better and more predictable outcome for their patients, they do so without placing themselves or their patients at a greater risk for cancer.
1. Just the Facts: Addressing Safety Concerns with INFUSE Bone Graft. Memphis, TN: Medtronic; 2012.
2. National Cancer Institute. Surveillance Epidemiology and End Results. Available at: http//seer.cancer.gov/seerstat/webhelp/standardized_Incidence_Ratio_and_Confidence_Limites.Htm
. Accessed November 14, 2011.