Cancer and altitude. Does intracellular pH regulate cell division?

Tissue culture growth rate is very sensitive to changes in pH of the external medium (H. Eagle), suggesting that the concentration in cells of +H or −OH might be the key factor controlling synthesis and eventual mitosis in normal and cancerous tissue. Since physiological acclimatization to higher altitudes produces changes in alkali-reserve in man and animals remaining at altitude, a possible correlation with statistics on cancer has been investigated. Available data on registrations of cancer (International Committee Against Cancer) and of cancer deaths (World Health Organization) have been analyzed for possible correlation of age-specific rates with a population-weighted mean altitude for each region surveyed. There is no “altitude-effect” below 60 or 65 years, but a statistically significant negative correlation ( r > 0·5. P < 0·05 in 8, < 0·01 in 7) was found for older ages in 15 of 16 sets of independent data. The drug acetazolamide has been used to produce “artificial acclimatization”, producing similar acid-base changes, and is reported (Evans) to have produced relief of intractable pain in terminal cancer patients. Some diseased states, such as achlorhydria and emphysema, in which there are chronic disturbances of acid-base relations, exhibit unexpected cancer rates. Some other possible explanations of the apparent “altitude-effect”, particularly that it is related to inefficiency of collection of data at high altitudes, seem implausible.