Feed A Fever, Starve A Cancer?

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 [1][4]. 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 [1], [3], [5][7]. 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 [1], [8]. 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 [9] and in the late of the last century in China [10]. 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 [9].

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.