Cancer and the Environment Gene-Environment Interaction (2002) / Chapter Skim
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5. Gene-Environment Interaction in Site-specific Cancers
5. Gene-Environment Interaction in Site-specific Cancers
Pages 46-59
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From page 46... ...
This is reflected in the high incidence rates observed for many racial-ethnic groups, both internationally and nationally. In the past 15-20 years, researchers have shed light on the etiology and risk factors involved in breast cancer, including reproductive hormones, genetic factors, and environmental factors.
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From page 47... ...
How this risk factor accounts for increased risk of breast cancer is a subject of intense research. 47 A very important and reliable predictor of breast cancer risk is the amount of estradiol in the blood of both pro- and postmenopausal women Brian Henderson Henderson described a long-standing focus on the role of sex steroids in the etiology of breast cancer, especially related to stimulation of the breast by estrogen and, more recently, progestin.
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From page 48... ...
BRCA2 was identified and cloned in 1995. Germline mutations in the BRCA1 or BRCA2 susceptibility genes result in breast cancers characterized by young age of onset, bilaterality, association with ovarian cancer and other tumor types, vertical transmission, and distinct tumor phenotypes.
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From page 49... ...
These examples illustrate the clinical value of addressing the genetic basis of cancer and the importance of understanding genetic mechanisms in developing methods of cancer prevention, early detection, and targeted therapies. Other genetic factors have been examined in addition to BRCA1 and 2.
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From page 50... ...
There are about 47 million current smokers and 44 million former smokers in the United States. Both groups are at increased risk of developing lung cancer, although current smokers have the higher risk.
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From page 51... ...
Lung cancer risk from smoking is dependent on the dose of tobacco carcinogens, which is modulated by genetic polymorphisms in the enzymes responsible for carcinogen activation and detoxification, as well as by the efficiency of the host cells in monitoring and repairing DNA damage due to tobacco carcinogens. Individuals with susceptible genotypes (or adverse phenotypes)
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From page 52... ...
We know that DNA repair capacity declines with advancing age, however, the youngest cases seem to have the poorest DNA repair capacity. Margaret Spitz Molecular Pathogenesis of Lung Cancer John Minna of the University of Texas Southwestern Medical Center and other investigators have hypothesized that clinically evident lung cancers have accumulated 10-20 different genetic abnormalities in dominant oncogenes, or tumor suppressor genes.
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From page 53... ...
Minna called for studies to identify the specific genes involved at these multiple sites and to determine whether these provide new tools for early molecular detection, monitoring of chemoprevention efforts, and identification of specific targets for developing new therapies. COLORECTAL CANCER Risks for Colorectal Cancer Colorectal cancer remains the third leading cause of cancer deaths in each sex and the second leading cause overall in the United States.
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From page 54... ...
The genetic basis for the development of colorectal cancer involves the accumulation of specific somatic mutations in proto-oncogenes and tumor suppressor genes with increasing age, said Raymond DuBois of the Vanderbilt University Medical Center (Figure 5-2~. However, only a small proportion of colorectal cancers are attributable to inheritance of these rare, highly penetrant mutated genes.
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From page 55... ...
Environmental factors may interact with metabolic genetic polymorphisms via a model in which the exposure alone, but not the variant genotype alone, increases disease risk, and exposure interacts with the variant genotype to further increase risk in exposed individuals. The same interaction can also modulate disease pathogenesis, in that exposure and susceptibility factors may alter the effects of other risk factors.
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From page 56... ...
PROSTATE CANCER Prostate Cancer: Epidemiology, Hormones, and Diet Prostate cancer is the second leading cause of cancer deaths in men in the United States today. Currently, researchers have identified age as being one of the two most important risk factors for prostate cancer.
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From page 57... ...
In addition, not all mammals have high rates of cancers. Only man and dog have been shown thus far to have a high naturally occuring incident rate of prostate cancer (Coffey, 1993~.
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From page 58... ...
In the men with prostate cancer, PC-SPES decreased serum testosterone concentrations, and in those and other patients, it decreased serum concentrations of PSA. The batches of PC-SPES studied contained estrogenic compounds that were distinct from diethylstilbestrol, estrone, and estradiol.
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From page 59... ...
Not long ago, the role of inherited susceptibility in human cancer was considered to be quite small. However, recent progress in identifying and characterizing highly penetrant, but relatively rare, susceptibility genes has furthered our understanding of genetic mechanisms and their role in cancer etiology.
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