© 2000 by Oxford University Press
Journal of the National Cancer Institute, Vol. 92, No. 1, 1A-1a,
January 5, 2000
© 2000 Oxford University Press
MEMORANDUM FOR: Science Writers and Editors on the Journal Press List
Genetics May Explain Women's Higher Risk of Smoking-Related Lung Cancer
December 29, 1999 (EMBARGOED FOR RELEASE 4 P.M. EST January 4)
More frequent expression of the gastrin-releasing peptide receptor (GRPR) gene in women than in men may help explain women's greater risk of smoking-related lung cancer, according to an article in the January 5 issue of the Journal of the National Cancer Institute.
Data from other studies suggest that the risks for all major types of lung cancer, at every level of exposure to tobacco smoke, are from 20% to 70% higher in women than in men. Gastrin-releasing peptide and its receptor—GRPR—are known to play a role in the promotion of lung cancer. The gene encoding GRPR is located on the X chromosome, and women have two X chromosomes and men have one. Ordinarily, the genes on one copy of the X chromosome in women remain inactive, but the GRPR gene has been shown to be functional on both X chromosomes in women. Thus, Sharon Shriver, Ph.D., at the University of Pittsburgh Cancer Institute, and colleagues, tested the hypothesis that women have more frequent airway expression of GRPR.
The authors worked with mainstream bronchus and peripheral biopsy specimens from 38 women and 40 men, including 58 patients with lung cancer. Primary cultures of bronchial epithelial cells and lung fibroblasts were established from these biopsy specimens. GRPR messenger RNA expression was determined for each of the cultures.
Among nonsmokers, no men and 55% of the women were positive for GRPR messenger RNA. For smokers with less than 25 pack-years of exposure (a pack-year is one package of 20 cigarettes smoked daily for one year), 20% of the men were positive, compared with 75% of the women. At exposures above 25 pack-years, the differences between male and female smokers disappeared. The authors say that these results indicate that the GRPR gene is expressed more frequently in women who do not smoke than in men who do not smoke, and that the expression is present or activated at an earlier time in women smokers.
Another experiment involved exposure of cultured lung fibroblasts to levels of nicotine found in the bloodstream of smokers. Such exposure increased GRPR messenger RNA by about 12-fold, suggesting that nicotine may be an important modulator of GRPR gene expression, the authors say.
The authors conclude that molecular markers such as GRPR expression may help to identify individuals at risk for developing lung cancer, especially women.
Contact: Barbara Kennedy, Penn State, College of Science Public Information Office, (814) 863-4682; fax (814) 863-2246.
Note: This memo to reporters is from the Journal staff and is not an official release of the National Cancer Institute (NCI) or Oxford University Press (OUP) nor does it reflect NCI or OUP policy. In addition, unless otherwise stated, all articles and items published in the Journal reflect the individual views of the authors and not necessarily the official points of view held by NCI, any other component of the U.S. government, OUP, or the organizations with which the authors are affiliated. Neither NCI nor any other component of the U.S. government nor OUP assumes any responsibility for the completeness of the articles or other items or the accuracy of the conclusions reached therein.
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