Microchips and cancer: a review

The VETMED email list had a discussion of the potential link between implanted identification microchips and cancer. I did some research to see what has been published on this topic.

A lot of our assessments of risk are based not on evidence, but on general impressions, as in "Everybody says [something commonly held to be true]" or "I've never seen [some rare adverse effect]." But sometimes, what "everybody says" is wrong. I prefer to look for evidence from scholarly studies when figuring out the risks of a specific drug or device.

When you look at scholarly research, you may not find the large-scale studies that would give you an accurate, quantified assessment of risk. Some years back, one of my dogs had his broken hock rebuilt by an orthopedic surgeon. I wanted to know whether we should remove the implanted bone nails and plates after he recovered, because some implantable devices, such as hip replacements in human patients, are associated with an increased rate of cancer.

When I discussed this with his surgeon and with other vets, it turned out that none of them could give me any evidence-based statistics on the incidence of bone cancer or other malignant neoplasms at the site of bone fixation devices. So, being the curious type, I looked at some of the research on that. I never did find any firm numbers, but what I found was the following things were all associated with an increased risk of cancer: Breaking a bone, implanting metal into the body, and implanting many other types of material into the body. Basically, it seems like anything that encourages more bone to grow increases the bone cancer risk (Goldschmidt and Thrall, 1985). (This is probably one reason that early-age spaying and neutering of dogs is associated with a significant increase in bone cancer risk. (Cooley et al, 2002 and Ru et al, 1998) Early desexing is known to produce taller animals. In intact dogs, the sex hormones of puberty help trigger the closure of the growth plates of the bones. If you spay or neuter a young puppy, the bones grow for a longer period and more bone growth increases the risk of bone cancer.

So, there is some risk of cancer from bone fixation devices, and the risk they pose is higher than the risk of simply breaking a bone - but I never did find research that quantified that specific risk. And I'm certain that the benefit of having a sound leg to walk and run on far outweighs the small risk of cancer from implanting bone fixation devices.

Going back to the issue of microchips, I did find multiple studies and some case reports that indicate that implanting a microchip raises the risk of cancer in animals.  Here are some relevant principles that we know from veterinary research on related risks:
  • Malignant tumors in animals have been linked to implantation of foreign bodies (Brand, 1975b and Moizhess, 1989). Even foreign bodies consisting of relatively inert materials such as glass (McCarthy, 1996 and Brand, 1975a) have been found to cause malignant tumors in animals.

  • Vaccinations and injections have been found to lead to sarcomas in cats (Kass, 2003), dogs (Vascellari, 2003), and ferrets (Munday, 2003). In the cat study by Kass, the sarcomas are not linked to one brand or type of vaccine, as was previously thought. (In some older studies, specific brands of vaccines were thought to be implicated, but some researchers now feel that was simply a reflection of the popularity of those brands.)

  • Inflammation, usually transient, occurs at the implantation sites of microchips (Mader, 2002, and Lambooij, 1995).

  • Tissue inflammation has a role in the development of cancer (Cousins, 2002, and Balkwill, 2001).

  • A fibrous capsule is formed around implanted microchips (Ball, et al, 1991, Gruys, 1993, Troyk, 1999) even in the absence of a gross inflammatory reaction (Jansen, 1999). This indicates that there is enough inflammation to cause fibrous tissue growth. Fibrosarcoma, which is the most common sarcoma associated with vaccinations in animals, is also rich in fibrous tissue.

So, if you're wondering how microchips could be harmful, the answer is that they can cause inflammation, fibrous tissue growth, and are implanted via injections, a method that is already known to increase the sarcoma risk. Then, add the fact that implanted foreign bodies are known to increase the risk of cancer. It follows that we have good reason to be cautious about microchip implantation.

When people want to dismiss out of hand the idea that there may be a cancer risk in implanting microchips, they should think about the many years that vaccines were given to cats before the issue of injection-site sarcomas was recognized and understood to be a risk.

I am not saying that the risk of implanting a microchip necessarily outweighs the benefit. I think each pet owner needs to decide that for themself. Vaccines are linked to sarcomas, but I vaccinate all my pets for rabies, because I believe the protection from a fatal disease is worth the small risk. The situation with microchips is different, as there are other identification methods available.

It would be unfortunate if the government mandated microchipping of pets and took this decision out of the hands of pet owners. There have been a few municipalities that have passed laws requiring this. I believe that the decision of whether to microchip an animal should be left to the pet owner, particularly since the owner is the one who will foot the bill for veterinary treatment in the case of any adverse effect.

Looking at the studies and case reports that link implanted microchips (also known as "passive transponders") to the development of tumors in various species of animal, it's interesting to note that most of the studies were not done specifically to find problems with microchips. Rather, the researchers implanted microchips in the animals they were using for some other study, and they noticed that their research subjects were developing tumors at the microchip implantation sites.

Some of these articles refer to specific lines of laboratory animals that may be more prone to cancer than the species as a whole. That's not a reason to dismiss the research. Just as some humans carry certain genes predisposing them to some form of cancer, a similar phenomenon is found in some dogs and cats. With implanted microchip devices becoming common as an identification method for pets, you have to assume that some of the dogs and cats that get them will have health issues, such as a genetic susceptibility to cancer. When deciding if a device or drug is safe, you don't just look at the risk to healthy animals, you have to look at the risk to the most vulnerable animals. too.

If anyone wishes to repost or republish this, please email me and ask for permission. I usually say yes, but I like to be asked.

Copyright 2006, S. Pober.
All rights reserved.
Contact the author.


REFERENCE LIST

Ball DJ, Argentieri G, Krause R, Lipinski M, Robison RL, et al. (1991) "Evaluation of a microchip implant system used for animal identification in rats." Laboratory Animal Science, 1991 Apr; 41:185-86

Balkwill F and Mantovani A. (2001) "Inflammation and cancer: back to Virchow?" The Lancet, 2001 Feb 17; 357(9255):539-45.
<http://www.thelancet.com/journals/lancet/article/PIIS0140673600040460/abstract>

Brand KG, Buoen LC, Brand I. (1975a) "Foreign-body tumorigenesis induced by glass and smooth and rough plastic. Comparative study of preneoplastic events." Journal of the National Cancer Institute, Aug 1975; 55(2):319-22.
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1159820>

Brand KG, Buoen LC, Johnson KH, Brand I. (1975b) "Etiological factors, stages,and the role of the foreign body in foreign body tumorigenesis: a review." Cancer Research, Feb 1975; 35(2):279-86.
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1089044>

Cooley DM, Beranek BC, Schlittler DL, Glickman NW, Glickman LT, and Waters DJ. (2002) "Endogenous gonadal hormone exposure and bone sarcoma risk." Cancer epidemiology, biomarkers & prevention, 2002 Nov; 11(11):1434-40.
Full text available:
<http://cebp.aacrjournals.org/cgi/content/full/11/11/1434>

Cousins, LM and Werb Z. (2002) "Inflammation and Cancer." Nature, 2002 Dec 19; 420, 860-867.
<http://www.nature.com/nature/journal/v420/n6917/abs/nature01322.html>

Gruys E et al. (1993) "Biocompatibility of glass-encapsulated electronic chips (transponders) used for the identification of pigs." Veterinary Record, 1993 Oct 16; 133(16):385-8.
<http://veterinaryrecord.bvapublications.com/cgi/content/abstract/133/16/385>

Jansen JA et al. (1999) "Biological and migrational characteristics of transponders implanted into beagle dogs." Veterinary Record, 1999 Sep 18; 145(12):329-33.
<http://veterinaryrecord.bvapublications.com/cgi/content/abstract/145/12/329>

Kass, PH et al (2003). "Multicenter case-control study of risk factors associated with development of vaccine-associated sarcomas in cats." Journal of the American Veterinary Medical Association, 2003 Nov 1; 223(9):1283-92.
<http://avmajournals.avma.org/doi/abs/10.2460/javma.2003.223.1283>

Lambooij, E. (1995) "Electronic identification with injectable transponders in pig production: results of a field trail on commercial farms and slaughterhouses concerning injectability and retrievability." Veterinary Quarterly, 1995 Dec; 17(4):118-23.
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=8751271>

Mader, C.H. et al. (2002) "Implantation of transponders at the bottom of the ear in equines" Berliner und Münchener Tierärztliche Wochenschrift. 2002 May-Jun; 115(5-6):161-6.
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=12058588>

McCarthy PE et al. (1996) "Liposarcoma associated with a glass foreign body in a dog." Journal of the American Veterinary Medical Association, 1996 Aug 1; 209(3):612-4.
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=8755980>

Moizhess TG and Vasiliev JM. "Early and late stages of foreign-body carcinogenesis can be induced by implants of different shapes." International Journal of Cancer, 1989 Sep 15; 44(3):449-53.
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=2777411>

Munday JS, Stedman NL, and Richey LJ. (2003) "Histology and immunohistochemistry of seven ferret vaccination-site fibrosarcomas." Veterinary Pathology, 2003 May; 40(3):288-93.
Full text available:
<http://www.vetpathology.org/cgi/content/full/40/3/288>

Goldschmidt MH and Thrall De. (1985) "Malignant Bone Tumors in the Dog" in Newton, CD and Nunamaker DM. Textbook of Small Animal Orthopaedics., Lippincott Williams & Wilkins, 1985.
<http://cal.vet.upenn.edu/saortho/chapter_74/74mast.htm>

Ru G, Terracini B, and Glickman LT. (1997) "Host related risk factors for canine osteosarcoma." Veterinary journal, 1998 Jul; 156(1):31-9.
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=9691849>

Troyk, Philip R. (1999) "Injectable Electronic Identification, Monitoring, and Stimulation Systems." Annual Review of Biomedical Engineering, 1999; 1:177-209.
<http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.bioeng.1.1.177>

Vascellari M et al. (2003) "Fibrosarcomas at presumed sites of injection in dogs: characteristics and comparison with non-vaccination site fibrosarcomas and feline post-vaccinal fibrosarcomas." Journal of Veterinary Medicine. A, Physiology, Pathology, Clinical Medicine, 2003 Aug; 50(6):286-91.
<http://www.blackwell-synergy.com/doi/abs/10.1046/j.1439-0442.2003.00544.x>

Articles Linking Microchips (Transponders) AND Tumors

[Where possible, I've quoted an excerpt from the abstracts or articles. Follow the links for the full abstracts or full-text.]

Vascellari M, Melchiotti E, Mutinelli F.
Fibrosarcoma with typical features of postinjection sarcoma at site of microchip implant in a dog: histologic and immunohistochemical study.
Veterinary Pathology. 2006 Jul; 43(4):545-8.
<http://www.vetpathology.org/cgi/content/abstract/43/4/545>
"A 9-year-old, male French Bulldog was examined for a subcutaneous mass located at the site of a microchip implant. [...] A diagnosis of fibrosarcoma morphologically similar to feline postinjection sarcomas was made. Fibrosarcomas at the site of injections have been reported in dogs and ferrets. Furthermore, neoplastic growth at the site of microchip implant in dog and laboratory rodents has been described."

Le Calvez S, Perron-Lepage MF, Burnett R.
Subcutaneous microchip-associated tumours in B6C3F1 mice: a retrospective study to attempt to determine their histogenesis.
Experimental and Toxicologic Pathology. 2006 Mar; 57(4):255-65. Epub 2006 Jan 19.
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=16427258>
" Fifty-two subcutaneous tumours associated with microchip were collected from three carcinogenicity B6C3F1 mice studies. Two of these 52 tumours were adenocarcinoma of the mammary gland located on the dorsal region forming around the chip. All the other 50 were mesenchymal in origin and were difficult to classify on morphological grounds with haematoxylin-eosin."

Vascellari M, Mutinelli F, Cossettini R, Altinier E.
Liposarcoma at the site of an implanted microchip in a dog.
Veterinary Journal. 2004 Sep; 168(2):188-90.
Link to conference presentation on this subject by the authors:
<http://www.aipvet.it/APIVMeetings/2003_ATTI_APIV/vascellarireprint2003.PDF>

European Medicines Agency, CHMP Safety Working Party. CHMP SWP Conclusions and Recommendations on the Use of Genetically Modified Animals Models for Carcinogenicity Assessment. 2004 June 23.
Full text:
<http://www.emea.eu.int/pdfs/human/swp/259202en.pdf>
[From Section 3, "C57BL/6(N5) - TRP53 KNOCKOUT (page 2)]
"3.2.1. Spontaneous Tumour Incidences

The overall spontaneous tumour incidence in studies of 26 weeks duration was low, 2.8% in males (n=283) and 6% in females (n=284) in studies without transponders (microchip implants for identification), and 8% in males (n=150) and 11.3% in females (n=150) in studies with transponders. Lymphomas, subcutaneous sarcomas and osteosarcomas were the three most common tumours. Other tumours had a much lower incidence (0.0-0.2%_).

Implantation of transponders results in particular in higher incidence of spontaneous sarcomas with up to 6.7% in female mice (as compared to 1.4% in females without biochips). The use of this method is therefore not recommended. It has also been suggested that displacement of the transponder can be induced by handling whihc may result in confounding tumours at a site distant from that of the implantation site. "

Floyd E, Mann P, Long G, Ochoa R.
The Trp53 hemizygous mouse in pharmaceutical development: points to consider for pathologists.
Toxicologic Pathology. 2002 Jan-Feb; 30(1):147-56.
Full text available:
<http://www.toxpath.org/stp_journal_archive/VOL%2030,%20NO%201,%20PART%20NA,%202002.PDF>
" Use of implanted electronic transponders can increase the incidence of sarcomas."

Elcock LE, Stuart BP, Wahle BS, Hoss HE, Crabb K, Millard DM, Mueller RE, Hastings TF, Lake SG.
Tumors in long-term rat studies associated with microchip animal identification devices.
Experimental and Toxicologic Pathology. 2001 Feb; 52(6):483-91.
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=11256750>
" Tumors surrounding implanted microchip animal identification devices were noted in two separate chronic toxicity/oncogenicity studies using F344 rats. The tumors occurred at a low incidence rate (approximately 1 percent), but did result in the early sacrifice of most affected animals, due to tumor size and occasional metastases. No sex-related trends were noted. All tumors occurred during the second year of the studies, were located in the subcutaneous dorsal thoracic area (the site of microchip implantation) and contained embedded microchip devices. All were mesenchymal in origin and consisted of the following types, listed in order of frequency: malignant schwannoma, fibrosarcoma, anaplastic sarcoma, and histiocytic sarcoma. The following diagnostic techniques were employed: light microscopy, scanning electron microscopy, and immunohistochemistry. The mechanism of carcinogenicity appeared to be that of foreign-body induced tumorigenesis."

Cohen SM, Robinson D, MacDonald J.
Alternative Models for Carcinogenicity Testing
Toxicological Sciences. 2001; 64:14-19
Full text available:
<http://toxsci.oxfordjournals.org/cgi/content/full/64/1/14>
" With respect to the sarcomas, it is important to distinguish between those occurring at the site of transponder implantation (used for identification) versus those that arise at other sites. Those related to transponders may be more likely related to foreign body sarcomagenesis rather than being chemically related."

European Society of Toxicologic Pathology. (2000) "MICROCHIP-ASSOCIATED TUMOUR IN A C57/BL MOUSE"
GTP [Gesellschaft für Toxikologische Pathologie] Meeting 2000: Case No 15.
<http://212.227.190.64/eurotoxpath/meetings/index.php?id=2000/case15>
" In a long-term study using 2554 mice, the possible influence of parental radiation exposure on tumour development in the descendants was investigated." [...] "In single animals of this ongoing study, circumscribed subcutaneous nodules occurred at the site of implanted microchips. A firm, pale white nodule, up to 30 mm in diameter, completely embedding the microchip completely was found in a 39-weeks-old female C57BL mouse." [...] "Researchers/pathologists must be aware of foreign body tumorigenesis (microchip-induced neoplasms) possibly complicating the interpretation of data from carcinogenicity studies."

Blanchard KT, Barthel C, French JE, Holden HE, Moretz R, Pack FD, Tennant RW, Stoll RE. Transponder-induced sarcoma in the heterozygous p53+/- mouse.
Toxicologic Pathology. 1999 Sep-Oct; 27(5):519-27.
Full text available:
<http://www.toxpath.org/stp_journal_archive/VOL%2027,%20NO%205,%20PART%20NA,%201999.PDF>
" Heterozygous p53+/- transgenic mice are being studied for utility as a short-term alternative model to the 2-yr rodent carcinogenicity bioassay. During a 26-wk study to assess the potential carcinogenicity of oxymetholone using p-cresidine as a positive control, glass/polypropylene microchips (radio transponder identification devices) were subcutaneously implanted into male and female p53+/- mice. During week 15, the first palpable mass was clinically observed at an implant site. This rapidly growing mass virtually quadrupled in size by week 25. Microscopic examination of all implant sites revealed that 18 of 177 animals had a subcutaneous histologically malignant sarcoma. The neoplasms were characterized as undifferentiated sarcomas unrelated to drug treatment, as indicated by the relatively even distribution among dose groups, including controls. An unusual preneoplastic mesenchymal change characterized by the term "mesenchymal dysplasia" was present in most groups and was considered to be a prodromal change to sarcoma development. The tumors were observed to arise from dysplastic mesenchymal tissue that developed within the tissue capsule surrounding the transponder. The preneoplastic changes, including mesenchymal dysplasia, appeared to arise at the transponder's plastic anchoring barb and then progressed as a neoplasm to eventually surround the entire microchip. Capsule membrane endothelialization, inflammation, mesenchymal basophilia and dysplasia, and sarcoma were considered unequivocal preneoplastic/neoplastic responses to the transponder and were not related to treatment with either oxymetholone or p-cresidine."

Tillmann T, Kamino K, Dasenbrock C, Ernst H, Kohler M, Morawietz G, Campo E, Cardesa A, Tomatis L, Mohr U.
Subcutaneous soft tissue tumours at the site of implanted microchips in mice.
Experimental and Toxicologic Pathology. 1997 Aug; 49(3-4):197-200.
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=9314053>
" An experiment using 4279 CBA/J mice of two generations was carried out to investigate the influence of parental preconceptual exposure to X-ray radiation or to chemical carcinogens. Microchips were implanted subcutaneously in the dorsolateral back for unique identification of each animal. The animals were kept for lifespan under standard laboratory conditions. In 36 mice a circumscribed neoplasm occurred in the area of the implanted microchip. Females were significantly more frequently affected than male mice. An influence of age or different treatment on the s.c. tumour incidence in two mice generations could not be observed. Macroscopically, firm, pale white nodules up to 25 mm in diameter with the microchip in its center were found. Microscopically, soft tissue tumours such as fibrosarcoma and malignant fibrous histiocytoma were detected."
Copyright 2006, S. Pober. All rights reserved.
Contact the author.
 The above article originally appeared on the VETMED discussion list in December 2006.
VETMED is a moderated discussion of veterinary and animal health issues.
To subscribe to VETMED, send email to:
      listserv@iupui.edu.
In the body of the message, type:
      SUB VETMED Yourfirstname Yourlastname

Last updated 9 December 2006.