Advances & Insights: Cancer
What the news means for you
John J. Rinehart, MD
Hematology and Oncology
Further research needed to understand differences
This study is based on epidemiological studies, which are often very difficult to verify and repeat. So until another study confirms the findings of the Multiethnic Cohort Study and the mechanism underlying the possible racial and ethnic differences is understood, we have to treat this report as preliminary. Problems with these kinds of data are related to the retrospective nature of the evaluations and bias of both the investigators and the subjects.
"The most useful outcome of this study would be investigations into why African-Americans may have a higher incidence of lung cancer."
The most useful outcome of this study would be investigations into why African-Americans may have a higher incidence of lung cancer even if they smoke a relatively small number of cigarettes. For example, there could be a gene that encodes for an enzyme that inactivates one of the carcinogens in cigarette smoke. This gene may occur less frequently in African-Americans than in Caucasians.
Thus, the importance of this study is that it points scientists in the direction of trying to discover a disease mechanism. Another advantage is that it could alert certain subsets of the population to greater dangers, such as smoking. At the same time, the results shouldn't be misinterpreted to mean it's safe for Caucasians to smoke.
There is a definite genetic predisposition to developing lung cancer, but so far the mechanisms are not well understood. Research has demonstrated an increase in lung cancer among family members when there is an absence of mitochondrial oxidase, a detoxification gene. At the same time, there are other families that have an increased incidence of lung cancer not associated with this, or any other known gene.
Lung cancer is one of the more genetically complicated cancers. It is likely lung cancer patients have been exposed to such a high dose of cancer-causing agents for so long that they have a very large number of genetic abnormalities in the tumor cells. There are at least 50 abnormal genes involved in lung cancer.
So many genetic changes are induced by lung cancer, it's a challenge to sort out which will be useful targets for treatment. We do know certain genes are key. For example:
- Gene p53, which is a tumor suppressor in many cancers, may be underexpressed in those who develop lung cancer, while
- Genes such as EGFR and VEGF, which are known to promote cancer, may be over expressed.
We already have drugs that target EGFR and VEGF genes, but they don't cure the cancer. It may be that we'll have to target multiple genes.
"We could eliminate 90 percent of [lung cancers] if cigarette smoking were eliminated."
Cure rates low
Our success at treating patients with lung cancer is not great. Of the 170,000 people who develop this disease each year, 90 percent will die. Survivability of lung cancer for the earliest stage of the disease (stage 1), when there is just the tumor but no clinically detectable spread to other parts of the body, is 60 percent. In stage 2, when the cancer is spread to local lymph nodes, the curability is 40 percent. If the tumor spreads further to regional lymph nodes (stage 3) only 20 percent of the patients are cured.
These disappointing clinical outcomes are the result of undetectable, microscopic spread of cancer cells at the time of diagnosis. Once the cancer has spread past the lymph nodes to the liver, bones or other distant sites, the overall cure rate is zero (stage 4). Unfortunately, lung cancer is not usually discovered until symptoms are present and patients have stage 3 or 4 disease. That's why the development of successful screening for early stage lung cancer is such a high priority in lung cancer research.
Studies now are focusing on CAT scans of the chest as the best method of screening for high-risk patients. The first question is, will this be effective in improving the cure rate, and second, will it be cost-effective?
One sure cure
We know the cure for most lung cancers. We could eliminate 90 percent of them if cigarette smoking were eliminated. Unfortunately, nicotine is a powerfully addictive drug. Once a person starts smoking as a teenager, the chances of stopping are small. The greatest hope for the cure of lung cancer is effective international governmental action to eliminate use of tobacco.
Dr. Rinehart is a hematologist/oncologist at the UK Markey Cancer Center and a professor of internal medicine at the UK College of Medicine.
Ethnic, racial differences may affect lung cancer risk
Cigarette smoking, which accounts for 80 to 90 percent of all lung cancer cases, poses varying degrees of risk among people from different racial and ethnic backgrounds. The American Lung Association reports that African-Americans develop and die from the disease more frequently than those in any other group, although the reasons have remained unclear.
African-Americans develop and die from lung cancer more frequently than those in any other racial or ethnic group.
Now, a new study presenting more convincing evidence of this racial disparity suggests genetics may be a factor. The Multiethnic Cohort Study, reported in the Jan. 26, 2006, issue of The New England Journal of Medicine, is one of the largest, most sophisticated to date supporting the existence of ethnic and racial differences in the smoking-related risk of lung cancer.
Researchers at the University of Southern California at Los Angeles and the University of Hawaii examined these differences in a study involving 183,813 African-American, Japanese-American, Latino, Native Hawaiian and white men and women. They analyzed 1,979 cases of lung cancer identified over an eight-year period, between baseline (1993-1996) and 2001, examining the effect of smoking history and habits on the risk of lung cancer.
Participants in the study were 45 to 75 years old. They were selected from a pool of 215,000 people who completed a questionnaire about their diet, education, demographics, occupation, personal behavior, prior medical conditions and family history of cancers. Respondents with a history of lung cancer or other smoking-related cancers were excluded. A follow-up questionnaire was administered in 2003.
The incidence rates for lung cancer were broken down according to smoking history:
- those who never smoked
- former smokers and
- current smokers.
The rate of current smoking among men was highest among African-Americans (28.5 percent) and Native Hawaiians (20.1 percent) and lowest among Japanese-Americans (15.5 percent).
Among those who smoked 10 or fewer cigarettes a day and those who smoked 11 to 20 cigarettes per day, the relative risk of smoking-related lung cancer was greatest among African-Americans and Native Hawaiians. Adjusting for diet, education and socioeconomic factors, researchers found that whites who smoked up to a pack a day had a 43 percent to 55 percent lower risk of lung cancer than blacks who smoked the same amount. Hispanics and Japanese-Americans were 60 to 80 percent less likely than blacks to develop the disease. At smoking levels of 30 cigarettes or more, the risks were similar among the five groups.
Genetics may play a part in making African-Americans more susceptible to tobacco carcinogens.
Suspected risk factors
Lung cancer is the leading cause of cancer-related deaths for all races and sexes in the United States. But according to the American Lung Association, black men are 50 percent more likely to develop the disease than white men and 36 percent more likely to die.
Other studies have pointed to a variety of possible reasons for these differences, including a tendency for black smokers to favor menthol cigarettes and inhale more deeply, along with diet, occupation and access to health care. Researchers in the Multiethnic Cohort Study do not directly address reasons, but they do suggest that genetics may play a part in making African-Americans more susceptible to tobacco carcinogens.
"Variation in the metabolism of nicotine among different ethnic and racial populations may underlie differences in smoking behavior (i.e., the depth and frequency of inhalation) and, thus, the uptake of carcinogens," they wrote. More research is needed, they noted, in assessing these differences in metabolism.
In an editorial accompanying the study findings, Neil Risch, PhD, of the University of California at San Francisco, wrote, "The explanation for the observed racial or ethnic variation remains to be determined. Unmeasured environmental variations, genetic differences, or both may be involved."
He also acknowledges that the concept of race affecting disease could be a controversial one since it has led to discrimination in the past. However, he notes, "Denying the existence of racial or ethnic differences in gene frequencies, some of which may contribute to the disease or treatment response, is unlikely to benefit minority populations."
For more information, see:
- Ethnic and racial differences in the smoking-related risk of lung cancer, The New England Journal of Medicine, v. 354, no. 4, January 26, 2006
- Lung cancer, Health Information, UK HealthCare
- Facts about lung cancer, American Lung Association
- Marty Driesler Cancer Project, Markey Cancer Center, UK HealthCare
- Kentucky Lung Cancer Research Program, Markey Cancer Center, UK HealthCare
UK HealthCare Cancer Services - Markey Cancer Center
For more information, or to make an appointment with a UK HealthCare physician, please call UK Health Connection at 1-800-333-8874.