leisure time activity and lower cancer risk

There have been a plethora of articles in the past year on the beneficial effects of exercise. I will use the next several blogs to sample some of these.

One article looked at the beneficial effects of leisure-time physical activity on 26 cancer types (see exercise and cancer jamaintmed2016 in dropbox, or doi:10.1001/jamainternmed.2016).

Details:

-- 1.44 million participants from 12 prospective US and European cohorts had self-reported leisure-time physical activity at baseline (1987 to 2004). Leisure-time physical activity levels were assessed as cohort-specific percentiles on a continuous basis. Hazard ratios are based on high vs lowactivity levels (comparing the 90^th versus 10^th percentiles of activity)

-- median age 59 years, 57% females, BMI 26.

-- 186,932 participants with cancer were included in the analysis

-- moderate activity in general was defined as intensity of >=3 more METS; vigorous activity as >=6 METS (see below for a definition for METS, or Metabolic Equivalents)

Results:

-- there was a lower risk for 13 cancers with higher levels of leisure-time physical activity (the statistical models controlled for age, sex, smoking, alcohol, race/ethnicity, education; as well as specific risk factors for some cancers, such as hormone therapy, age at menarche, age at menopause, and parity for several of the female-only cancers, etc):

    -- esophageal adenocarcinoma, decreased 42%, HR 0.58 (0.37-0.89)

    -- liver, decreased 27%, HR 0.73 (0.55-0.98)

    -- lung, decreased 26%, HR 0.74 (0.71-0.77)

    -- kidney, decreased 23%, HR 0.77 (0.70-0.85)

    -- gastric cardia, decreased 22%, HR 0.78 (0.64-0.95)

    -- endometrial, decreased 21%, HR 0.79 (0.68-0.92)

    -- myeloid leukemia, decreased 20%, HR 0.80 (0.70-0.92)

    -- myeloma, decreased 17%, HR 0.83 (0.72-0.95)

    -- colon, decreased 16%, HR 0.84 (0.77-0.91)

    -- head and neck, decreased 15%, HR 0.85 (0.78-0.93)

    -- rectal, decreased 13%, HR 0.87 (0.80-0.95)

    -- bladder, decreased 13%, HR 0.87 (0.82-0.92)

    -- breast, decreased 10%, HR 0.90 (0.87-0.93)

--but there were higher risks of:

    -- malignant melanoma, increased 27%, HR 1.27 (1.16-1.40)

    -- prostate cancer, increased 5%, HR 1.05 (1.03-1.08): but specifically for non-advanced prostate cancer (HR 1.08), with no association for advanced prostate cancer (HR 0.99)

-- cancers that did not reach statistical significance included non-Hodgkin’s lymphoma (though this was borderline significant at the P=0.05 level,with an 8% decrease with increased leisure-time activity), thyroid, gastric non-cardia, soft-tissue, pancreas, lymphocytic leukemia, ovary, and brain

-- controlling for BMI decreased the statistical significance for esophageal carcinoma, and rendered the associations with endometrial cancer, liver and gastric cardia to be nonsignificant

-- associations were generally similar with overweight/obese versus normal weight individuals

-- smoking status modified  the association for lung cancer but not the other smoking-related cancers

Commentary:

-- this observational study found the quite impressive result that exercise was associated with major decreases in 13 cancers (10, after adjusting for BMI), and the decrease was 20+ % (ie, really large) for 7 of them.

-- There are obvious concerns with such a study, including the fact that they compared only the top 10^th percentile to the lowest 10^th percentile of leisure-time activity, which also likely includes more unaccounted-for biases (e.g., those in the highest percentile group being much more likely to have generally healthy lifestyles, which may not be fully reflected in the multivariate analysis). Also, as with any meta-analyses, there are bound to be significant differences in the methodology of each individual study, making the strict combination of them less rigorous. The measures of physical activity were self-reported, and the cutpoints of high vs low varied between the individual studies. Also, some of the measurements (e.g. BMI) were considered as dichotomous variables (either above or below 25) which could conceal their true contribution (i.e. a BMI of 25.1 may confer a very different risk from a BMI of 35.1; on the other hand a BMI of 24.9 may not be so different from a BMI of 25.1)

-- Another issue is that leisure-time activity reflects only part of the picture. Many of the old studies only looked at leisure-time activity because they could not figure out how to incorporate work-related activity into the metric. Work-related activity requires very detailed analyses of individual workplaces, given that people doing the same job in different workplaces may have amounts of physical exertion, depending on such factors as degree of automation, how large the workplace is and what the division-of-labor is, and, in general, how the specific job was structured, including the role of labor unions requiring employers to decrease the intensity or potential risks of many jobs. Also, since leisure-time activity typically reflects voluntary participation, that would reinforce the above-stated potential bias that these people lead generally healthier lifestyles.

--another recent systematic/meta-analysis (see physical activity and mortality bmj2016​ in dropbox, or http://dx.doi.org/10.1136/bmj.i3857) included 174 world-wide studies, looked at the levels of total physical activity (leisure-time, occupational, domestic, transportation) and the risk of breast cancer, colon cancer, diabetes, ischemic heart disease, and ischemic strokes, finding:

    --overall, major gains for all outcomes occurred at lower levels of physical activity (3000-4000 MET minutes/week)

    --even 600 MET/week (the lowest level in the studies), had a 2% lower risk of diabetes (vs no reported physical activity)

    --but going from 600 to 3600 MET minutes/week reduced the risk additionally by 19%. further increases did not add much (eg, 0.6% if increase from 9000 to 12000 MET minutes/week)

    --at higher levels of physical activity (>8000 MET minutes/week), they found:

        --14% reduction in breast cancer

        --21% reduction in colon cancer

        --28% reduction in diabetes

        --25% reduction in ischemic heart disease

        --26% reduction in ischemic stroke

    --but, looking at the curves: for all endpoints but breast cancer, there was the most dramatic improvement going from about 1500 to 4000 MET minutes/week, with leveling off thereafter. for breast cancer, the curve showed a relatively linear decline with more activity. [remember: this study included all physical activity: ie it is hard to translate the current US recommendation of 75-150 minutes/week of exercise into the above 1500-4000 MET minutes/week.]​

-- Potential mechanisms connecting exercise with decreased cancer include: decreased body fat (body fat could confer various risks, including increased estradiol levels; they did note that BMI did decrease the association with several cancers, however I would add that BMI is not the most specific measurement of body fat, and does not differentiate from the much more metabolically active and less healthy visceral fat from subcutaneous fat); also many/most hormonal systems are changed with exercise, including cortisol levels (which in themselves affect most other hormone levels), male and female sex steroids, insulin and insulin-like growth factors, and adipokines (and many of these hormone systems could be related to carcinogenesis, eg by altering immune function); as well as changes in inflammation, oxidative stress (which are especially related to  visceral fat), and the reduced colonic transit time which could affect colon cancer incidence.

So, a pretty quick and dirty study, but it does really reinforce the potential role of exercise in cancer prevention. This becomes even more of an issue given the predictions that the global cancer burden will increase dramatically (one model suggesting a doubling by the year 2030), especially as unhealthy lifestyles such as smoking and poor diet increase in resource-poor countries: there are increasing obesity trends and less physical activity as more people move to crowded and often quite polluted cities -- these changes are associated with a pretty dramatic shift from mortality associated with infectious diseases to that associated with chronic, western-type diseases).

from blog of 1/3/17 on cardiovascular fitness as a vital sign:

-- as a quick guide to METs:

    --light activity (<3 METs): includes walking 2.5 mph (2.9 METs)

    --moderate activity (3-6 METS): includes walking 3.0 mph (3.3 METs), walking 3.4 mph (3.6 METs), stationary biking (light effort) 5.5 METs

    --vigorous activity (>6 METs):  jogging (7.0 METs), calisthenics/pushups/situps (8.0 METs), rope jumping (10.0 METs)​