on the basis of Knudson's 'two-hit' hypothesis ..
The multi-stage hypothesis was first suggested over 50 years ago based upon an analysis of the age-specific incidence data , . This data consists of a histogram of the age at which a population develops cancer. It has long been interpreted to suggest that four to six rate-limiting events are required for the formation of cancer.
This is the "first hit," according to Knudson's hypothesis.
I tested the validity of the parallel routes hypothesis with the most powerful dataset available, the Surveillance Epidemiology and End Results 17 registries (SEER-17) data collected in the year 2000 for the age-specific incidence of colon carcinoma. The year 2000 data monitored 73 million people in the United States and recorded over 22,000 cases of colon carcinoma. The population under surveillance, an important factor, was directly measured by the 2000 US Census data. Thus, this is the best data to use to test this hypothesis.
For example, there are 55 clockwise and 89 counterclockwisespiralslying on the surface of the sunflower; thus sunflowers are said to have55, 89 phyllotaxis.
Two hit hypothesis: Knudson Loss of heterozygosity ..
Prostate carcinoma age-specific incidence data was consistent with the parallel route hypothesis until 1991, see . The 1991 time period corresponds to the widespread adoption of the PSA serum test for prostate cancer screening. The PSA test was first approved in 1986, but it was initially used only to monitor the progress of prostate cancer patients. In 1991 a study showed that the best method of screening for prostate cancers is measurement of serum PSA levels combined with digital rectal exams. This radically changed the diagnosis procedure for prostate carcinoma.
An Example of a Confidence Interval and a Hypothesis Test ..
However, as a comprehensive analysis and synthesis by Neher (1996) argues, the concept is unscientific because (1) it is based on the discredited notion of the inheritance of acquired characteristics; (2) it does not allow for the variation in specific archetypes that is a basic aspect of genetics; and (3) it is not grounded in a convincing elimination of the possible influence of socialization and culture in the personal, therapeutic, and cross-cultural examples on which it is based.
( Knudson’s two hit hypothesis) ..
The parallel routes hypothesis was consistent with the age-specific incidence date for lung and colon carcinomas for all 32 years. However, the results for prostate and breast carcinoma were more complicated. See . Detailed graphs of the data, along with the parallel routes hypothesis, are shown for 2003 in . A table presenting the fraction of the population that is susceptible to the disease is shown in .
Knudson called this the two-hit hypothesis of cancer.
Finally, I applied this hypothesis to better understand the racial disparity in breast cancer. This striking disparity exists in the prognosis for breast cancer patients in the United States. Although African-Americans are less likely to contract the disease, a significantly larger percentage of these patients die from it, compared to white patients. Furthermore this gap has been increasing over the past few decades . While the obvious cause, unequal treatment, may be responsible for some of this disparity, it is not responsible for all. A detailed study of over 20,000 breast cancer patients treated in the equal access Department of Defense Health care system between 1980 and 1999 also revealed a consistent and growing disparity .
Hypothesis Definition, Checklist, and Examples
For the next test of the hypothesis, I used the SEER-9 data to perform 31 similar tests (one for each year from 1973 to 2003) on the four most common types of carcinoma: lung, colon, breast, and prostate carcinoma. The SEER-9 data monitors fewer people than the SEER-17 data, but has been collected since 1973. Using this data allows more independent tests of the hypothesis.