FAMILY HISTORY, CARDIOVASCULAR DISEASE and CANCER
Abstract: The knowledge that our parents or siblings experienced major disease - and especially if they experienced disease at a fairly young age - warns us that we also can have a much higher genetic risk of this major disease than average. Family history risk may be the largest of all known risk factors for cancer. Although we may not be able to change our genetic susceptibility, it becomes of far greater importance to reduce our actionable risks if a family history of disease is known. Life Ahead quantification of the risks of family history together with other elevated risks can provide a much more very serious warning about the need for improved health habits than has previously been available.
The Largest Potential Risk: An important health risk – and it can be the largest of all of our risks - is that related to our basic genetics. The Life Ahead program now identifies the health risks of an average US population having specific life habits. These risks may be computed with reasonable accuracy for the average population, perhaps within 10-15% for various diseases at different ages. But for any combination of these risks, individuals within this population can have much higher or lower that average risk. Consider a major disease or death from it that will develop from a given set of Life Ahead risks and habits at age 60 in the average population. Some in the population will get it at age 50 and others not until age 70. A tiny few might get it as early as age 40, and a tiny few others will live past 80 without ever experiencing it. These differences in actual risk and experience are due to our differing genetics.
Hopefully, more knowledge about our DNA and what it can mean about our risk of disease may help identify these genetic differences in our risk in the future. But today the main clue you have may be the disease history of your family members.
The Life Ahead Analysis: Results of about 50 different research values of family risk were used in developing the Family Health Risk module in the Life Ahead program. Some studies provided several different individual risks for different family combinations and factors. A most important factor was the age at which a family member first contracted a disease. For example, a mother having breast cancer at age 40 revealed a far more serious risk than that of a mother that had breast cancer first at age 75. If two parents contracted a disease the risk of an offspring was higher than if one parent had the disease. And interestingly, if a sibling as brother or sister contracted a disease this identified a still higher risk than if a parent had the disease. All of these other risks were age-related. For example a mother contracting a disease at age 35 would confer a higher risk than a sibling that had it at 60.
The risk factors from this research were analyzed via statistical regression to identify how these various family relationships developed overall risks for differing diseases. The statistically based formula derived is appended here as formula (1). Some risk ratios from this formula are as follows:
Age of Family Member at First Disease 35 50 60 75
Risk if one Parent had Disease 4.5 2.5 1.7 1.1
Risk if two Parents had Disease 7.1 3.9 2.6 1.8
Risk if Sibling contracted Disease 9.7 5.3 3.6 2.0
These risks are for all diseases, as heart disease, stroke, and various types of cancer. It was not possible within the scope of the analysis to identify differing factors for different diseases. For example the family history factors were roughly similar for cardiovascular diseases and cancer within the margin of error of studies reviewed and for the very large effects of relationship and age at disease. Also, it was not possible to identify different family risks for different types of cancer. A family member disease of one type of cancer increased risk of any type of cancer for a user. It seems likely that breast cancer of a parent would increase selectively the breast cancer risk of a child vs. risks of other cancers. Although this probably is true, it was not possible to identify this added specific risk quantitatively in this analysis. An effort will be made in the future to refine family risk further.
These family related risks become very high when a family member and especially a brother or sister obtained a disease at age 50 or lower, or two parents have a disease. The higher risk associated with disease of a sibling suggests that there are combined genetic components of risk obtained from both parents that apply to any of their children.
Problems with Family Risk: There are at least three problems with using these family risk values directly in Life Ahead. First, they are gross risks. A person’s risk is measured vs. that of the average population. If parents had high risk factors as for example smoking, diet, and exercise their earlier disease could be due partly to risks from their habits rather than from genetics. Smoking rates have come down sharply in the past few decades, and thus part of our reduction in health risk in recent years is due to people smoking less than did their parents. There is some small correlation between cholesterol of parents and that of their children, and other habits probably are similarly correlated to some extent. A seriously missing factor in studies of family risk was the absence of unusual health risk factors for parents that could have been carried over to their descendants.
A second problem is that Life Ahead now includes an extensive valuation of multiple risks for habits that was not previously available that should explain a portion of the risk difference between parents and children. Three new included risks are Total Cholesterol genetic factor, HDL genetic factor, and Cardiofitness genetic factor. These risks identify part of an individual’s genetic risk vs. the average population and these almost certainly will be partly family related. This combination of identified individual risks and genetic risks should reduce the portion of still unknown family risks for cardiovascular diseases. But the remaining family risk for cancer still remains substantial, and is less well accounted for now via Life Ahead factors than is the risk of cardiovascular diseases. The risk of breast cancer that often develops at ages before 50 is very strongly family related.
A third problem is that limits must be imposed on any statistical formula such as the one appended as their values cannot extrapolated. These limits as others in Life Ahead are imposed at the higher values actually measured in research. Gross family risks of up to 6 to 7 times were measured, and thus the limiting value of gross risk is 7. A lowest value of risk of 1.1 is taken for any identified family disease history at any age.
Use of Family History Risk in Life Ahead: The present Life Ahead program assigns 50% of gross family related risks as defined in the table above and in formulas below to a user's risk of cardiovascular diseases, and 2/3rds of gross family related risks to a user's risk of all causes of cancer. This reduces the remaining component of genetic risk somewhat by allowing for some inter-family related risk factors and to recognize the above and other factors included in Life Ahead that were not considered in family history research. If the family member that had the disease was a cigarette smoker and the user is a non-smoker, only one third of the gross risks family related risk was assigned for coronary disease and one half to cancer. Such allowances are obviously only rough estimates. But even allowing for this, our genetic risks still may comprise the largest unknown in forecasting our future risk of major disease and length of healthy life. And Life Ahead estimates of these risks probably are conservative.
Family Risk is a "Non Actionable" Factor that Shows a Key Need for ACTION: We probably cannot do anything to change a basic genetic risk identified from the experience of other family members. But recognition of a family risk raises a large red flag about the need for serious health action. Life Ahead can forecast a likely termination of healthful life at before age 50 for 30 year old individuals with high family history risks and two or more other important health risk factors. With this warning there are important things people CAN do about it. This is to reduce the risks that can be controlled. Better life habits can make an even more important than the usual difference in the length of healthful life for those that have family history risks. Life Ahead can provide specific estimates of the extraordinary risks that can accompanying high combinations of family and other risks, and can suggest how these risks probably can be lowered substantially. .
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(1) Formula for gross family history risk of disease:
sibling = 0 if no sibling contracted disease; = 1 if 1 or more had disease. Parents then = 0
Parents= 0 if 1 contracted disease; = 1 if 2 or more contracted disease
disease-age is age at which family member contracted disease
Minimum risk accepted = 1.1
Maximum risk accepted = 7.0
Family risk ratio = exp (2.89 + 0.77 * sibling + 0.463 * parents - 0.0397 * disease-age)