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 EXERCISE and CANCER

Abstract:  Eighty nine comparisons from fifty one different research studies now show that the exercise that produces Cardiofitness will produce substantial reductions in the risk of cancer.  The higher intensity exercise that produces Cardiofitness efficiently is much more effective in reducing risk of cancer than is gross Activity Calories of physical activity.  Cancer at each differing body site appears to be reduced near equally by the kind of exercise that improves Cardiofitness.  Cancer risk from exercise probably develops only gradually over time as is true for the effect of cigarettes.  Thus individuals probably must  maintain needed exercise for long durations to obtain effective benefit in reducing risk of cancer.

A Poorly Recognized Fact:  One of day’s best kept health secrets revealed convincingly by Life Ahead is this:  A proper amount and kind of exercise maintained over long periods of time may be the most effective of all known lifestyle ways to reduce risk of cancer. Wide publicity has been given the fact the exercise protects against heart disease. The fact that exercise can reduce cancer risk nearly as effectively as it reduces heart disease risk seems to be less widely known.  

An enormous amount of research has been published relating risk of various types of cancer to exercise, physical activity, and Cardiofitness. Surprisingly, no adequate review the “170 different research studies” cited to have been done could be found here.  All studies found in a Medline search were reviewed in the Life Ahead project.  A problem with some of this research is that exercise often was identified by trivial questions such as “Do you exercise regularly?” or “How many times per week to you exercise” etc.  Answers to such questions do not identify the actual amount, kind, duration, and intensity of exercise needed for any useful quantification of cancer risk vs exercise.  Such studies are useful but only for citing a generality as “Exercise reduces risk.”   The more important question is “What amount and kind of exercise will reduce what kinds of cancer by useful identified amounts.”   

The Actual Research:  A reading of the various papers reveals a wide consensus that physical activity is beneficial, but with the usual statistical confusion of a few studies that found benefits that did not reach the 95% level of significance. Research on physical activity and cancer involves quite high margins of error in part because valuations of the actual physical activity depend on answers to questionnaires that have not always asked the really pertinent questions.

Yet when organized on a consistent basis - perhaps for a first time -  the results of 89 listed different risk comparisons from 51 different studies relating exercise, physical activity, and Cardiofitness to the risk of cancer provide an impressively convincing picture of benefit. These results are shown in Table C following.  Risks of cancer are reduced by more exercise or physical activity in nearly every comparison.  These include all of the studies found useful for obtaining an approximate answer to the above key question.  Risks of cancer shown in the Table C are for differing amounts of occupational physical activity, leisure time exercise, combinations of both occupational and leisure activity, and for actual differing levels of Cardiofitness.

Two key measures of physical activity cited in Table C are differences in Physical Activity calories, and differences in Cardiofitness. Except for the 10 actually measured values of Cardiofitness, all valuations of Activity Calories and other Cardiofitness values are estimates that are only  approximate.  Some estimates of Activity Calories were based on specific questionnaires submitted by participants and provided by study authors. Others were from tables of Activity Calories associated with various kinds of physical activity.

Cardiofitness and Activity Calories:  Activity calories and Cardiofitness differ mainly in their valuation of intensity of exercise.  The Calorie basis assumes that low level and high levels of physical activity contribute similarly to results, as 5 hours at a low 100 calorie level contributes the same as 1 hour at 500 calories level.  The Cardiofitness basis values high levels of activity as much more effective in producing benefit.  Cardiofitness will give little credit for 5 hours at the low 100 calorie level and far more credit for the physical activity at the 500 level.

Cardiofitness is a direct and probable casual factor that explains differences in risk of heart disease.  Its benefit can be reconciled via mechanisms that can explain its effect quantitatively. Cardiofitness also is a directly measurable condition of the human body. In contrast there is no known body measurement that can identify a specific expenditure of Activity Calories, and no identified mechanisms that can explain quantitatively their benefit.  The intensity level of Activity Calories can be more important to reduction of health risk than is their gross amount, and no clearly identified quantification of activity level and activity amount has yet been derived.   

Serious questions become:  “Is the risk of cancer associated best with differing Calorie amounts of exercise, or with levels of Cardiofitness?”   And  "Is higher intensity exercise more effective in reducing cancer risk than low intensity exercise"
 

This question about the type of physical activity that is most effective cannot be answered from results of any individual study.  Individual health studies usually show only statistical associations, and cannot identify which of various associations is the true cause and effect. A most probable answer as to true cause can be derived be determining first from a Global Analysis of all research which basis best explains the results ALL research study results, and second, which basis is most  consistent with other known facts from biochemistry.  The Global Analysis develops an an answer that best fits the very wide range of different kinds of exercise included in the 89 different study comparisons. The answer to the first of these questions was clear:

Correlation coefficient of risk of cancer with Cardiofitness:             0.78          t = 11.5

Correlation coefficient of risk of cancer with Activity calories          0.41          t =  4.2

The correlation with the Activity calorie basis was poor.  In contrast, the 0.78 value of Cardiofitness is not only a quite high value but is confirmed as valid at above 1000 to 1. Best individual comparisons revealing the importance of cardiofitness are those from study #49 that includes very high measured levels of Cardiofitness from what probably was mostly efficient aerobic exercise from relatively modest numbers of Physical Activity Calories.   

This result is somewhat surprising when applied to risk of cancer.  Cardiofitness measures the robustness of the heart and its accompanying cardiovascular system.  It seems near obvious why this measure provides for protection against heart disease.  But cancer proceeds via quite different mechanisms.  The fact that correlation of cancer benefit with Cardiofitness is so much better than that with physical activity calories does not prove that the key protective agent is is same Cardiofitness measure that reduces risk of heart disease.  Rather, this impressively better correlation reveals that cancer is protected better by more intensive levels than by low levels of exercise. Cardiofitness credits the value of more intensive exercise selectively.  Activity calories assumes all calories, low and high intensity act similarly.  Thus Cardiofitness may act only as a useful "marker" of the amount and intensity of exercise that effectively protects against cancer.

Cardiofitness that protects against heart disease develops from increased exercise over a period of 6 months, and can be lost after 6 months of no exercise.  Risk tends to follow this same path.  Cancer tends to develop very slowly, with 20 or more years for precursors to evolve into a first physical evidence of its existence.  Exercise and preferably more intense exercise probably acts to slow the progress of cancer somewhat during the period of its development.  More on this follows later.

Effect of Cardiofitness on Individual Causes of Cancer:  The effect of Cardiofitness on risk of individual causes of cancer is interesting and also is surprising.  Most studies show risks ratios of cancer for those having more exercise in the range of 0.45 to 0.65.  At higher levels of Cardiofitness risk ratios are low as 0.2 are noted.  There is a general pattern of higher risk ratios for those that exercised more and developed higher cardiofitness.  Thus the risk ratio per unit increase in HEF provides a useful measure of benefit.  The results following show the average risk reductions in cancer per unit of HEF in fitness from all useful research found.

Cancer Cause                   Average reduction in Risk       5%-95%       No of Risk  

                                            per unit increase in HEF          Limits       Comparisons

Any Cancer                                         3.7%                             2.9-4.5              11

Colorectal Cancer                              3.3%                             2.3-4.3              12

Prostate Cancer                                  3.9%                             2.3-5.5               8

Breast Cancer                                     4.5%                             3.7-5.4              31

Endometrial +Ovarian Cancer          4.4%                             3.9-4.0              13

All Comparisons                                4.0%                             3.6-4.4              89

The average value from all 89 comparisons of 4% benefit per year per unit increase in HEF is statistically consistent with the individual values for each individual cause of cancer. This implies a risk factor for cancer of about 0.66 for a usual higher value of about 10 HEF for people who are more vs. less active.  Too few risk ratios for Lung and Pancreatic Cancer were available for a statistical analysis, but risks for these cancers also appear similar to the above values.  Overall, it appears that effective exercise benefits all types of cancer near equally.

Because Cardiofitness is a marker of the risk of cancer from physical activity, a further question is:  “Are the present estimates of Cardiofitness valid?”  Taken individually, these estimates are recognized as approximations only.  A test of this question is to compare risk ratios obtained from actually measured values of fitness with those from estimated values.  The average cancer risk from 10 comparisons based on measured values of Cardiofitness is 3.5% (limits 2.7-4.3%) per HEF.  The average cancer risk from 79 other estimated values of Cardiofitness (on somewhat different causes) is 4.2% (limits 3.8-4.9%) per HEF.  Although this suggests a small upward bias in using estimated values, and that estimated values of Cardiofitness may be a bit underestimated, the results remain statistically consistent.   Thus taken overall, the results of all 89 comparisons support that relationship of cancer risk with the exercise that also improves Cardiofitness.

Other Factors Involved in Risks of Cancer from Exercise:   No clear difference was noted between risks of men and women on either colorectal or all causes of cancer.  No significant differences in the effects of occupational or leisure time exercise could be identified when using the Cardiofitness basis for estimating equivalent exercise.  But a given number of the more intensive activity calories from leisure exercise usually would reduce risk substantially more than will the same number of less intensive physical activity calories obtained from occupational physical activity.

A probable effect of exercise timing and duration on risk of cancer emerges from the research. Studies #3, 24 and 36 found that risks measured in earlier years combined with more recent risks to produce best risks. Studies #7, #35, and #38 examined and found lifetime long activity to be of benefit. Although an early report on the Nurses study (J Natl Cancer Inst 90:1155) found no effect of teen age exercise on later breast cancer, study #33 found that women that were athletes in college had lower risks at later ages, and study #23 found a small effect of early exercise on future risk. This pattern found in the research shows that exercise develops its benefits over many years of life, and thus depends on its duration.  Any factor affecting the risk of cancer would be expected as for that of cigarettes to be duration related.  

The actual risk ratios measured via the research in Table C are for unknown durations of difference in physical activity and Cardiofitness.  Occupational physical activity may be fairly consistent over 20-30 years or more.  But leisure time exercise activity of individuals usually is more variable. A usual estimate of factor duration in population research studies is 10 years as is used for antioxidants and diet.  On this basis an improvement in Cardiofitness of 10 HEF will produce after 10 years duration an overall improvement in cancer risk of 4% per HEF or a risk ratio of 0.66.  At 20 years of a Cardiofitness duration the expected risk ratio for a difference of 10 HEF will be 0.44.  For conservatism Life Ahead imposes a limit of 130 HEF for computation of Cardiofitness benefits and 20 years maximum for duration, and a minimum risk factor of 0.30 for any amount and duration of a Cardiofitness advantage.  Six risk actually measured study risk ratios in Table C are at or below this assumed minimum.

Life Ahead now computes risk of exercise on cancer from a profile of HEF by age and from a moving average of a past 20 years of risk ratios for cardiovascular equivalent exercise.  This method can show how high exercise in teen or college years will produce a modest benefit after age 30 and before age 40 even if improved fitness is discontinued after age 22.  This result now has been observed in some research. This basis simulates the actual results found in the research to date for exercise over time and produces after 10 years duration the average risks measured from all 89 research comparisons.  This produces a more conservative valuation of the risk of exercise than would obtained by simply applying the average risk factor at age as is done in statistical type models.

On the debit side, accomplishing a recommended improvement in the exercise that improves Cardiofitness at present age via this model probably will not produce an immediate large reduction in risk of cancer.  A near full reduction in potential risk of cancer probably will not be achieved until after many years of a new exercise is maintained.  This differs from the effect of Cardiofitness on cardiovascular disease that is assumed to operate as more directly casual. The effect of Cardiofitness on the robustness of the heart and cardiovascular system and on probable risk of disease can develop or disappear within a time of 6 months.

The Mechanism for Cancer reduction via Cardiofitness improvement:  No clear mechanism via which Cardiofitness improves cancer risk has been found.  Speculation on possible causes has been bowel transit time for colorectal cancer, testosterone levels, and improvement in the immune system.  The new observation that cancer risk on all sites benefits near equally from Cardiofitness improvement suggests only the immune system as a remaining likely candidate.  But research to date has not shown exercise to be particularly effective in improving the immune system. 

Another possibility may be that the infusion of added oxygen into the blood over time – and this is the clear benefit of the aerobic type exercise that produces Cardiofitness – may be involved.  Oxygen radicals are negative factors, but free oxygen infusion might have beneficial effects.  A useful hypothesis for exercise and risk of cancer requires identification of a causative agent can slow the general process of cancer development that proceeds throughout the entire body over time.