Can flagyl, particularly long term use, cause cancer?
A 1998 study that concludes that short term use does not cause cancer: http://www.journals.uchicago.edu/doi/pdf/10.1086/516306
But then there is this:
Is Metronidazole Carcinogenic?
By: Andres Bendesky ; Daniel Menendez ; Patricia Ostrosky-Wegman ; Daniel Menendez ; Patricia Ostrosky-Wegman
Format: Article Peer Reviewed
Published in: Mutation Research/Reviews in Mutation Research Jun2002, Vol. 511 Issue 2, p133 12p 13835742
Metronidazole (MTZ, 1-[2-hydroxyethyl]-2-methyl-5-nitroimidazole), an antiparasitic and antibacterial compound, is one of the world's most used drugs. MTZ is potentially carcinogenic to humans due to the following facts: it is a proven mutagen in bacterial systems, it is genotoxic to human cells and also, it is carcinogenic to animals. However, due to inadequate epidemiological evidence, it is not considered as a risk factor for cancer in humans. As it will be discussed here, the existing population studies are deficient since they have not included sufficient sample size, the follow-up time has not been long enough, and the individual sensitivity to the drug might have been acting as a confounding factor. Due to the increasing use of this drug, more and improved studies are needed to elucidate its mechanism of genotoxicity and its carcinogenic potential. [Copyright 2002 Elsevier]
And a newer study (2008) is more disturbing, regarding the immunosuppressive role of flagyl:
Evaluation of immunosuppression induced by metronidazole in Balb/c mice and human peripheral blood lymphocytes
Mohammad Fararjeha, 1, Mohammad K. Mohammadb, Corresponding Author Contact Information, E-mail The Corresponding Author, Yasser Bustanjib, Hatim AlKhatibb and Shtaywy Abdallaa
aDepartment of Biological Sciences, faculty of science, The University of Jordan, Amman 11942, Jordan
bFaculty of Pharmacy, The University of Jordan, Amman 11942, Jordan; accepted 16 October 2007.
The immunomodulatory effect of metronidazole (MTZ), a nitroimidazole drug used as an antiprotozoal and antibacterial agent, was investigated using Balb/c mice and human peripheral blood lymphocytes. For in vivo studies, mice were divided into six groups, six animals per group, group I received vehicle alone while the other groups (II–VI) received intraperitoneal injections of MTZ (14, 28, 42, 57, and 114 mg/kg) respectively. For in vitro studies different concentrations of MTZ (5, 10, 50, and 200 μg/ml) were used. MTZ showed a significant decrease in the percentage of circulating neutrophils and monocytes and an increase in the percentage of circulating lymphocytes. The relative weights of spleen as well as the relative body weight gain also decreased. Detectable changes were seen in the histology of spleen and thymus. Splenic plaque-forming cells (PFC), hemagglutination (HA) titer to sheep red blood cells (SRBC), spleenocytes and human peripheral blood lymphocytes proliferation (MLR) were markedly suppressed by MTZ treatment as compared to control group. MTZ also induced a significant decrease in delayed-type hypersensitivity (DTH) reaction, phagocytic activity (assessed by phagocytic capacity and phagocytic index) as well as TNF-α secretion by peritoneal macrophages. These observations indicate that MTZ significantly induced immunosuppression in mice and in human peripheral blood lymphocytes.
And later in the article:
Despite the overt use of MTZ as an antibacterial and antiparasitic antibiotic in humans, there is little information about its potential influence on the immune system cellularity and function. MTZ has been shown to induce suppression in the bone marrow, a primary lymphoid organ, and to affect male fertility . Furthermore, it has been observed that MTZ induces DNA single-strand breaks in the lymphocytes of patients on standard doses of the drug  and , therefore toxicity to the peripheral lymphoid organs is suspected.
Gastrointestinal absorption of MTZ after oral administration is very fast and is comparable to intraperitoneal administration. In the present experiments, MTZ decreased the gain in body weight of MTZ-treated mice in all used doses over 14 mg/kg. Furthermore, all the tested doses of MTZ decreased the relative weight of the spleen, and the doses 42, 57 and 114 mg/kg body weight induced atrophy in the white pulp of the spleen. In addition, the dose 28 mg/kg induced atrophy in the medulla of the thymus, suggesting a possible effect on the activation and differentiation of the T-lymphocytes, an effect that might explain the relative increase in the circulating lymphocytes (Table 1). We have shown that the highest two doses (57 and 114 mg/kg) of MTZ decreased the percentage of neutrophils and at the same time increased the percentage of the lymphocytes at the same level of significance (p < 0.01), suggesting a suppression of the phagocytosis defense mechanism by neutrophils, therefore bactericidal activity inhibition is suspected. The decrease in the spleen relative weight and in the atrophy of spleen white pulp and thymus medulla may be the reason behind relative lymphocytosis because of lymphocyte primary and secondary lymphoid tissue homing suppression, a conclusion which is consistent with the finding that MTZ inhibits leukocyte-endothelial cell adhesion in rat mesenteric venules . Peripheral blood RBCs showed a decrease in number when MTZ was used in the highest dose which may be due to the suppression of the bone marrow . These parameters form, in part, the first level of tests for immunotoxicity screening . Since MTZ induced changes in these parameters, the results of the present work indicate that this drug causes modulation of the immune function.
In conclusion, the present study shows that MTZ has an inhibitory effect on the humoral as well as cell-mediated immune responses. The results demonstrate an immunosuppressive effect of MTZ in mice as well as in human lymphocytes. The effectiveness of MTZ in the treatment of diseases should be counterbalanced by the increasing evidence of its immunotoxicity. Further studies should be considered to study the significance of using MTZ in patients under long-term treatment.