SMOKING, CANCER and CARDIOVASCULAR DISEASE
Abstract: Cigarette Smoking increases the risk of heart and other cardiovascular disease, increases the risk of nearly every type of cancer, and increases the risk of nearly every cause of premature death. Risk from smoking develop slowly and can become substantial only after about 30 pack years (as smoking 20 cigarettes per day for 15 years). Health risk is related to the square root of number of cigarettes smoked, and thus the number smoked must be reduced from 40 to 10 per day or from 20 to 5 per day to halve smoking risk. Risk drops about 16% each year after smoking is stopped, but some risk can persist for up to 20 years for former heavy smokers. Cigar and pipe smokers have a much smaller increase in risk than do cigarette smokers. The vast research available on smoking provides basic information on the mechanisms by which carcinogens produce cancer which are often overlooked by researchers.
The #1 Research Study of Smoking: The premier and now classic research data on smoking were obtained by Hammond on more than a million men and women in the 1960’s. This study was published in various papers, and specifically in the National Cancer Institute Monograph #19. This data set appears unique in its scope. It identified all cause deaths, deaths from lung cancer and most other causes of cancer, and deaths from cardiovascular diseases. Further, it related these deaths to amounts of cigarettes and other types of smoking, to length of time cigarettes were smoked, to amount of smoke inhaled, to age of individuals and age smoking started, to time after smoking was stopped and all this for both men and women. No other data obtained since challenges the scope or conclusions obtainable from this massive study. Rather most other studies of smoking confirm or extend its conclusions somewhat.
The Life Ahead Analysis: The Hammond data were a primary basis for the Life Ahead model of cigarette and other smoking. A first analysis was made of the results for all causes of death because the data on this probably was most extensive. Hammond provided a total of 110 different risk ratios on cigarettes vs all causes of death for men and women for different amounts smoked, for various smoking ages of starting, stopping, and durations, for amounts inhaled and at differing ages. Many more risk ratios were included for deaths from Lung Cancer, Coronary Disease, and other causes. These data was first studied using dozens of stepwise multiple regressions to identify the probable causal relationships involved and how these causes operated to cause premature death.
It became clear that the primary cause of death from cigarettes was the product of number of cigarettes smoking and the time they were smoked. This has widely been confirmed as the “Pack-Years” effect of smoking. (A pack is 20 cigarettes). The problem in using a ratio such as this in a BioChemical level model is that this assumes the effect of each percentage increase in amount smoked is duplicated exactly by a similar change in time smoked. (This is not true as example for the widely used HDL/Total Cholesterol ratio). Thus assumption this was verified to be approximately true via the regressions for all and most other key causes death. An exception was noted however as will follow for Lung Cancer.
Risk of death was not found to relate directly to the Pack-Years smoked. Rather, risk related with best significance to the 0.5 power or square root of Pack-Years times the length of time smoked. This means is that reducing cigarettes from 2 packs per day to 1 pack per day does not reduce the risk of smoking in half. It takes a reduction from 2 packs to one-half pack per day to reduce risk in half. Or to halve risk, smoking must be reduced from 20 cigarettes per day to 5 per day.
The Formula for Cigarettes and Death from All Causes: All other factors that affect the risk of smoking must relate as factors to the primary variable of Pack-Years or Cigarette-Years (cigyrs). This becomes obvious because at a zero level of either numbers of cigarettes smoked or number of years smoked the risk ratio of smoking for any other combination of factors must become unity, and risk from smoking per se becomes zero. Thus conventional textbook regression or statistical methods cannot easily value smoking risks vs result variables. Also most of the risk factors for smoking identified in various population research studies have only very narrow validity. True risks of smoking are changing continually with time of smoking and user age. The formula finally developed for relating risk of all death to cigarettes from Hammond is appended as formula (1)
The primary causative factor is cigyrs, the number of cigarettes per day times years smoked. This formula satisfies the requirement of unity factor at either zero cigarettes or zero years. Risk is increased significantly by amount of ciginh, or amount inhaled. Even though this is a highly subjective estimate for different individuals, the effect of the inhale factor was found to be quite significant in Hammond’s research.
The risk of smoking as a ratio declines as men and women become older. Two cautions are noted here. First, observed risks usually are higher for those older, but this is mainly because older people smoke for more years, and this is included more properly in the cigyrs factor. Second, the overall risks of nearly all causes of death increase substantially with age. Thus a lower risk factor times the higher actual risk at higher age can produce a net overall risk that can become higher as individual become older despite a somewhat lower percentage risk. The sexf factor is noted as 1 for women, zero for men. This shows a slightly lower risk for women at all other similar conditions.
The Risk for Lung Cancer from Cigarettes: By far the highest risk for smoking is for Lung Cancer. For this cause of death the risks associated with cigarettes per day and time in years do not appear equal. Rather risk appear more directly proportional to time, but still are in proportional to cigarettes per day to the 0.5 power. Thus the “Pack years” effect is Cig/day ^ 0.5 * Yrs. The Life Ahead formula for risk is appended as (2). Increased risk of lung cancer from cigarettes can exceed 20 fold for heavy smoking for long periods of years.
The Risk for Breast Cancer from Cigarettes: There long has been controversy about the effect of cigarettes on breast cancer. Most studies published prior to about 1990 showed little or no effect of smoking on the risk of breast cancer. Other more recent studies (Palmer, Am J Epidemiol 134:1-13 and Calle, Am J Epidemiology 139:1001) found significant risks for smoking in the range of 1.7-1.8 times. A Swiss study (Morabia, J Epidemiology 143:918) found even larger risks. A brief review of 15 studies of smoking and breast cancer identified a probable reason for this discrepancy.
Cigarette smoking requires a long duration of time before cancer develops. And the risk of smoking develops as a function of pack years of smoking. For example, only a limited fraction of smokers develop lung cancer before 40 pack years of smoking. (See sections on Cancer and Smoking). This is particularly true for the development of breast cancer that develops even more more slowly than does lung cancer. Most breast cancer patients studied in research on smoking were in the age range of 30-50 years of age, and smoked about 15 cigarettes per day. Assuming an average starting age of 17-20, this will give only about 15 pack years of exposure, a far from adequate exposure for a development of breast cancer. It hardly is surprising that such studies would find little or no effect of smoking within their usual margin of error. Further, some researchers failed even to recognize the key importance of pack years of smoking. Attempting to relate risk separately to years smoked and to numbers of cigarettes smoked lowers even further the statistical power of the relationships for limited numbers of cigarettes and years smoked.
Calle found a breast cancer risk ratio of 1.74 for the smoking of 40+ cigarettes per day for a probable 40 pack years of exposure. Palmer found from each of two studies, one in the US and another in Canada, that smokers of more than 25 cigarettes per day that started before age 16 developed breast cancer risk ratios of 1.7(1.0-2.9) and 1.8(1.0-3.4) respectively. The large Nurse’s study (London J Natl Cancer Inst 18:1625) found no effect on breast cancer for an exposure of perhaps 30 pack years, but found a development at this time of tumors with a risk ratio of 1.38(1.04-1.84). A formula for breast cancer used in Life Ahead of appended formula (3) explains the risk ratios of the 15 studies reviewed on breast cancer reasonably well within their margins of error. Times and amounts of smoking are only roughly estimated by some of the research used in this analysis, and a more detailed and complete global analysis of smoking and breast cancer is needed. This formula produces a conservative risk ratio of just 1.5 for 40 pack years of smoking, and is used only to a maximum risk ratio of 2.0. The majority of women that experience breast cancer during their years before age 50 would not acquire a sufficient pack years of smoking for it to be a substantial contributor to their cancer. But as they smoke for much longer times this can become a significant additional contributor to breast cancer risk in their later years and significantly reduce their potential Well Days of life
Risks for Other Causes of Disease from Smoking: Most formulas for Life Ahead were derived initially from Hammond as modifications of formula (1) above. Differing effects for other diseases included those for Coronary Heart Disease, Other Heart Disease, Stroke, Breast Cancer, Prostrate Cancer, Female Genital Cancer, Colon Cancer, All Other Cancer, All Other Disease Death, Motor Vehicle Deaths, and Non-Disease Deaths.
The formula for the effect of smoking on Coronary Heart disease was also was checked vs results of the Report of the Pooling Project, American Heart Association Monograph #60. This study pooled the results of five major US studies of Heart Disease. Other smoking related causes of other disease were reviewed vs. other research studies published in the intervening years. Effects of smoking on genital, prostate, and colorectal cancer from Hammond and other research appear to be from nil to small.
A summary of effect of smoking on risk ratios of various disease causes of death for a man of age 50 that has smoked a usual 30 cigarettes per day from youth as included now in Life Ahead formulas follows. These assume average inhaling:
Years of Smoking 10 20 35
Disease:
Death from All Causes 1.57 1.84 2.19
Coronary Heart Disease 1.54 1.85 2.25
Stroke 1.31 1.47 1.67
Lung Cancer 1.70 2.91 6.47
Breast Cancer 1.13 1.28 1.53
Prostate Cancer 1.06 1.10 1.15
Genital Cancer (Women) 1.00 1.00 1.00
Colorectal Cancer 1.06 1.10 1.15
Other Cancer 1.46 1.72 2.05
Motor Vehicle 1.06 1.10 1.14
Lesser than average inhale factor reduces risk by about 10%, and the higher inhale factor increases risk about 10%. These effects for inhale level can increase for long periods of heavy smoking. The coronary risk ratio value for women at 35 years is 1.74 vs. the 2.19 for men.
Risks for Pipes or Cigar Smoking: Hammond showed that smoking of pipes and cigars did create risks of both Cancer and CVD, but at a much lesser level than that from cigarettes. This probably is due to the much lower amounts of such smoke that is inhaled. Life Ahead uses a simple factor of general pipe and/or cigar smoking as an added equivalent of 2.5 cigarettes per day. Although this is a rough approximation only, the risk level here does not deserve much refinement. The other factors as age and time of smoking apply similarly as for cigarettes. Keep in mind that the computed risk of 2.5 cigarettes per day is about half the risk of 10 cigarettes per day.
The Risk after Smoking is Stopped: The risk of most diseases from smoking declines at about 16% per year after smoking is stopped. After 1 year, the risk is 84% of that previous. After 5 years the risk drops below half to 42% of that when smoking. After 10 years only 18% of prior risk remains. This risk from Lung Cancer drops slightly faster at 18% per year. But because risk from this cause can become so high, some appreciable excess risk of Lung Cancer can remain 10 years after smoking is stopped.
The Research on Smoking Provides Basic Information about Carcinogens: The most extensive research data yet obtained relating the development of human cancer from carcinogens are from studies of men and women that smoked cigarettes over long periods of time. Surprisingly, there appears to have been little global study of this important data beyond its use in verifying the health debits of smoking. The research on cigarettes can tell us much more about cancer than the just the statistical risks of smoking. This research provides quantitative insights on how cancer develops, how cancer develops over time from exposure to carcinogenic agents, and how its risk declines after a major carcinogen is eliminated. These insights most probably will apply to the development of and regression of cancer from diet and other causative agents.
Perhaps most important is the long induction period usually needed to produce human cancer. This means that the 3 to 5 year clinical studies revered for obtaining health information on medicines and other health factors can be useless for measuring the effect of a factor on cancer. Such studies probably would fail to find any effect of cigarettes on either cancer or heart disease during this time period. Life Ahead shows that duration of exposure can be a factor a key importance to risk level of most health factors that can affect the duration of healthy human life.
Smoking produces tars that include carcinogens that contact directly the mouth, throat, and lungs, and digestive system. The section on Cancer notes that the effect of carcinogens is reduced by frequent washing that does occur in the digestive tract. But this washing is largely absent in the lungs, and the carcinogens gradually coat lung tissue and create the greatest increase in risk at this site. The breast and genital organs are not so directly contacted, and smoking produces a lower risk at these sites.
Smoking increases risk of Cardiovascular Diseases (CVD) by increasing the rate at which atherosclerosis builds up. (See the section on Atherosclerosis). This clogs arteries faster. This in turn appears due to the fact that smoking creates a pro-oxidant environment that increases the harm of LDL cholesterol.. Also, smoking may increase the clotting tendency of blood that can be involved in heart attacks.
The slow decline of risk after smoking is stopped is important from the standpoint of basic science. This demonstrates that even after a complete removal of a specific carcinogen - or after removal of an agent that increases atherosclerosis – the risk to health of this agent does not immediately disappear. Conventional risk factors and most health risk models assume risk to be immediately associated with a factor. Rather, risk of both cancer and cardiovascular diseases gradually builds up over long periods of time and then gradually moves down during the decade or two following removal of this factor. This behavior is specifically and perhaps uniquely quantified in Life Ahead via its Life Cycle mechanism for both cardiovascular diseases and cancer. _____________________________________________________________________________________
Sample Formulas:
(1) Risk of All Death = Exp ((cigyrs ^ 0.5) * (0.0249 + 0.00379 * ciginh - 0.00025 * age - 0.00874 * sexf))
(2) Risk of Lung Cancer Death = Exp ((cig/day ^ 0.5 * yrs)* (0.00989 + 0.00175 * ciginh - 0.00005 * age - 0.00337 * sexf))
(3) Risk of Breast Cancer from Smoking = Exp (0.010137 * pack years of smoking)
Note that risk must approach zero for either zero cigarettes or zero years of smoking. These formulas accomplish this.