Highlight HEALTH

The Washington Post published a story yesterday stating that Personal Health Beliefs are Largely Hit and Myth. The story discusses the results of an American Cancer Society (ACS) study released last week, which will be published in the September 1st issue of the journal Cancer. The study assessed the prevalence and sociodemographic correlates of scientifically unsubstantiated beliefs about cancer risk, finding that [1]:

… beliefs in several scientifically unsubstantiated cancer risk statements are relatively common among the participants in this study, and that the prevalence of such beliefs varies by certain sociodemographic characteristics.

Men were more likely to endorse scientifically unsubstantiated cancer risk beliefs than women. Other characteristics associated with lower health literacy included non-white race, Hispanic ethnicity, income below $30,000 and less than a high school education. Surprisingly, those people who considered themselves “somewhat informed” or “not very informed” about cancer, compared to those who considered themselves “very informed”, were less likely to agree with unsubstantiated cancer risk beliefs. The authors state that this result is consistent with previous research [2], demonstrating that people tend to overrate their own abilities and reach judgements with too much confidence. Remarkably, over two-thirds of those people surveyed believe that the risk of dying from cancer in the U.S. is increasing.

This simply is not true.

Back in January I wrote about the decrease in annual U.S. cancer deaths when the 2007 cancer statistics were published. The age-standardized cancer death rate has been decreasing since the early 1990s [3-4].

The ACS study reminded me of anther investigation published in May of this year that examined the sociodemographic correlates of fatalistic beliefs regarding cancer prevention [5]. Said another way, “what personal characteristics correlate with the belief that cancer is predetermined and inevitable?”

The study found the following with respect to fatalistic beliefs about cancer prevention:

• Nearly half of respondents agreed that “It seems like almost everything causes cancer.”
• Over one-quarter of respondents agreed that “There’s not much people can do to lower their chances of getting cancer.”
• A whopping 72% of respondents agreed that “There are so many recommendations about preventing cancer, it’s hard to know which ones to follow.”

The results were similar to the ACS study mentioned above, that is, that fatalistic beliefs about cancer are stronger among less educated Americans. A notable difference however in the results is that, when controlling for socioeconomic status (with the exception of Spanish-speaking Hispanics), the beliefs are either weaker or equivalent among African Americans and Hispanics compared with Whites. I must point out that these results are inconsistent with earlier investigations as well as the recent ACS study. The study’s relatively low response rate (34.5%) may be responsible for this inconsistency.

Family cancer history was linked to a stronger belief that “everything causes cancer”, which suggests a proximal cancer experience that raises perceived risk. Unexplainably, being married or living as married was associated with greater agreement of two of the three fatalistic beliefs.

These results are a cause for concern as fatalistic beliefs are associated with people NOT engaging in cancer prevention behaviors, including regular exercise, not smoking, and fruit and vegetable consumption. Individual beliefs in several scientifically unsubstantiated cancer risk statements may influence actual health-related behaviors and adherence to cancer screening guidelines. Indeed, although a few years ago the ACS estimated that half of all men and one third of women may develop some type of cancer in their lifetime [6], as much as 70% of all cancers are preventable through diet and lifestyle.

The take-home message? There is a great deal of misinformation and scientifically unsubstantiated health beliefs in the world today. Be extremely critical of what you read and hear. Demand to see the scientific data and base your beliefs on the evidence.

References

1. Stein et al. Prevalence and sociodemographic correlates of beliefs regarding cancer risks. Cancer. 2007 Jul 26; [Epub ahead of print].
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2. Dunning et al. Flawed self-assessment. Implications for health, education, and the workplace. PsycholSci Public Interest. 2004; 5: 69-106.
3. Jemal et al. Cancer statistics, 2007. CA Cancer J Clin. 2007 Jan-Feb;57(1):43-66.
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4. Ries et al. SEER Cancer Statistics Review, 1975-2003. National Cancer Institute, Bethesda, Md. Updated 2006.
5. Niederdeppe and Levy. Fatalistic beliefs about cancer prevention and three prevention behaviors. Cancer Epidemiol Biomarkers Prev. 2007 May;16(5):998-1003.
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6. Cancer Facts & Figures 2005. American Cancer Society. Atlanta, Ga. 2004.

The cell cycle is a series of ordered events that occur in a cell between it’s initial formation and eventual duplication and division into two daughter cells. Cells in the human body normally reproduce up to ~50 times [1], doubling their number with each cell cycle. Stem cells provide a pool of dividing cells to replace those that have died.

Interphase, the period between cell divisions, is where most cells remain for at least 90% of the cell cycle. Interphase consists of three phases: G1 (for gap 1), S phase (for synthesis) and G2 (for gap 2). During G1, the cell undergoes rapid growth and metabolic activity, including production of RNA and synthesis of protein. For the cell to divide and produce an identical copy of itself, its genome must be duplicated. DNA replication occurs in S phase. During G2, cell growth continues and the cell prepares for division. Cell division or mitosis occurs in M phase.

In normal cells, during G1 there are specific genes that control the speed of the cell cycle. These genes, called tumor suppressors and oncogenes, are mutated (meaning damaged) in cancer cells and can result in uncontrolled reproduction. Additionally, unlike normal cells, cancer cells do not stop reproducing after ~50 divisions. Thus, a cancer is an uncontrolled proliferation of cells.

Tumor suppressors

Tumor suppressors are genes that either slow down cell division, DNA repair or cell death (a process known as apoptosis or programmed cell death). These processes are all interconnected. Throughout the cell cycle there are DNA damage checkpoints; if there is damage, DNA replication is paused while the damage is repaired. In the event that the damage cannot be repaired, the cell initiates apoptosis. When a tumor suppressor gene is mutated (increasing either their expression or function) and inactivated (meaning turned off; also referred to as “loss of function”), cells can grow out of control and lead to cancer. As of 2003, 174 tumor suppressor genes were identified [2], including:

• Tumor protein p53 (p53)
• Adenomatosis polyposis coli (APC)
• Breast cancer 1, early onset (BRCA1)
• Breast cancer 2, early onset (BRCA2)
• Retinoblastoma 1 (RB1)

The analogy is often made between tumor suppressors and the brakes on a car. Just as the brakes keep a car from going too fast, tumor suppressors keep the cell from dividing too quickly.

Oncogenes

In contrast to tumor suppressors that are inactivated, oncogenes are permanently activated. Oncogenes are mutated forms of genes called proto-oncogenes that normally control cell division and the degree of differentiation (a process by which cells acquire “a type”). When a proto-oncogene is permanently activated (meaning turned on; also referred to as “gain of function”) through mutation, it is called an oncogene. When this occurs, cell division happens too quickly and cells can grow out of control and lead to cancer.

Some classic examples of proto-oncogenes are:

• Neuroblastoma RAS viral oncogene homolog (NRAS)
• v-Myc myelocytomatosis viral oncogene homolog (MYC)
• Epidermal growth factor receptor (EGFR)

Oncogenes are analogous to the accelerator on a car. Oncogenes “drive” the cell cycle, speeding up cell growth and division.

Two-hit hypothesis

In 1971, Alfred Knudson proposed the two-hit hypothesis for tumorigenesis [3]. While studying children with retinoblastoma (a cancer of the eye), Knudson noted differences between patients with inherited tumors and patients that appeared to have no susceptibility to the disease. Statistical analysis revealed that the fraction of cases not yet diagnosed in patients with the hereditary form of the disease decreased exponentially with age, suggesting that one mutational event caused the cancer.

His findings demonstrated that multiple mutational events or “hits” were necessary to cause cancer. Everyone has two copies of most genes, one from their mother and one from their father. Normally, one mutation is not enough for cancer to develop, unless you were born with it. This occurs with people who have familial cancer (meaning occurs in families). People who were born with a mutation in a tumor suppressor are predisposed to cancer and only need damage in the other copy for cancer to develop. Those born without the mutation require two mutational events to occur, statistically much less likely. However, there are cases where a single mutation is sufficient to cause an effect, notably the p53 gene.

The current view of cancer has built upon the two-hit hypothesis. Today, cancer is modeled as an accumulation of mutations in both tumor suppressors and oncogenes. Additionally, epigenetic changes (meaning something that affects a cell without changing its DNA sequence) [4] and microRNAs [5] play a role. Thus, a number of genetic and epigenetic alterations are thought to be required for tumor progression and the development of cancer.

The scope of this article is limited to a basic overview of the two general classes of genes that contribute to cancer. For a more information, Nature Milestones in Cancer highlights achievements made in cancer research since the end of the nineteenth century and provides historical perspective on how given concepts evolved.

References

1. L Hayflick. The limited in vitro lifetime of human diploid cell strains. Exp Cell Res. 1965 Mar;37:614-36.
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2. Yang and Fu. TSGDB: a database system for tumor suppressor genes. Bioinformatics. 2003 Nov 22;19(17):2311-2.
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3. AG Knudson. Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U S A. 1971 Apr;68(4):820-3.
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4. AP Feinberg. The epigenetics of cancer etiology. Semin Cancer Biol. 2004 Dec;14(6):427-32.
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5. Calin and Croce. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006 Nov;6(11):857-66.
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In 2003, cancer deaths in the United States decreased by 369 deaths compared to 2002, the first drop seen since 1930. In 2004, the decrease in cancer deaths was eight times greater - 3,014 deaths - than in 2003, according to a report published in the latest issue of the American Cancer Society (ACS) journal CA: A Cancer Journal for Clinicians [1].

Experts are attributing the decreases to declines in smoking, earlier detection and more effective treatment of tumors. The three most common cancers - breast, prostate and colorectal cancer - show a decrease in death rates, with the largest change from colorectal cancer. Experts attribute much of the credit for the reduction in colorectal cancer to screening exams and the early detection of polyps that can be removed before they become cancerous.

The cancers with the greatest decline in death rates from 1990 to 2003 for men were lung cancer (down 38.4%), prostate cancer (down 24.8%) and colorectal cancer (down 16.1%). The greatest decline in death rates from cancer for women were breast cancer (down 39.4%) and colorectal cancer (down 22.3%). However, primary cancers of the esophagus, liver and bile ducts are increasing in men, and lung cancer in women.

The CA article and its companion piece, Cancer Facts & Figures 2007, are yearly ACS reports that estimate the number of cancer cases and deaths for the coming year. In 2007, an estimated 1,444,920 new cases of cancer are expected, with 559,650 cancer deaths. For men, new cancer cases will include prostate cancer (29%), lung cancer (15%) and colorectal cancer (10%). For women, new cancer cases will include breast cancer (26%), lung cancer (15%) and colorectal cancer (11%).

Although inherited genes do influence the risk of cancer, heredity alone explains only a fraction of all cancer cases. The most important changeable determinants of cancer risk are not using tobacco, dietary choices and physical acitivty. The following recommendations by the ACS are suggested to reduce the risk of cancer, heart disease and diabetes:

1. Maintain a healthy weight throughout life.
2. Adopt a physically active lifestyle.
3. Consume a healthy diet with an emphasis on plant food sources.
4. Limit alcoholic beverage consumption.

References

1. Jemal et al. Cancer statistics, 2007. CA Cancer J Clin. 2007 Jan-Feb;57(1):43-66.
   View abstract