The gene is known as transforming growth factor beta-1 (TGF-beta-1).

Growth factors are gene products that help regulate cell division and tissue proliferation. The TGF-beta family has widespread effects on many aspects of growth and development, including the wound healing process.

TGF-beta is synthesized in many different tissues. According to information cited in the article, there is evidence that abnormalities in the TGF-beta pathway may be involved in the production of tumors (oncogenesis).

Animal experiments suggest that increased expression of the TGF-beta-1 gene is protective against early tumor development, particularly in breast cancer.

Elad Ziv, M.D., of the San Francisco Veterans Affairs Medical Center and the University of California, San Francisco, and colleagues analyzed data from 3,075 white women aged 65 and older to determine if there is an association between breast cancer risk and a variation of TGF-beta-1.

The women were recruited from four medical centers in the United States between 1986 and 1988 to take part in the study.

To determine if there is an association between variations in the TGF-beta-1 gene and the risk of breast cancer, the authors measured the frequency of three specific genotypes (C/C, T/T, and T/C) among the women who took part in the study.

The frequency of the C/C genotype was 14.9 percent; 48.6 percent of the women had the T/C genotype; and 36.7 percent of the women had the T/T genotype.

The authors then looked at breast cancer cases during an average follow-up of 9.3 years, verified by medical chart review, and compared genotype to the occurrence of cancer. Over the 9.3 years of follow-up, 146 women developed breast cancer.

"Risk of breast cancer was similar in the 1,124 women with the T/T genotype (56 cases; 5.4 per 1,000 person-years) and the 1,493 women with the T/C genotype (80 cases; 5.8 per 1,000 person-years), but was significantly lower in the 458 women with the C/C genotype (10 cases; 2.3 per 1,000 person-years)," the authors report.

"In analyses that adjusted for age, age at menarche (first menstrual period), age at menopause, estrogen use, parity, body mass index, and bone mineral density, women with the C/C genotype had a significantly lower risk of developing breast cancer compared with women with the T/T or T/C genotype [64 percent decreased risk]" the authors write. "There was no significant difference between the risk for women with the T/C genotype compared with women with the T/T genotype."

"About 85 percent of the women in our study had at least one T allele [T/T or T/C] for the TGF-beta-1 gene, which was associated with a 2.5- to 3-fold increased risk of breast cancer in comparison with women who had the C/C genotype," the authors report.

"If the T allele is regarded as a risk factor for breast cancer, then the population-attributable risk associated with this allele is approximately 60 percent."

"Thus, if this association is real and causal, this allele is associated with a substantial fraction of cancers among older white women in the United States," they conclude.

The authors note that an important limitation of the study was that women in the study group were all older than 65 years. As a result, the study did not address the relation between TGF-beta-1 genotypes and breast cancer in younger women. (JAMA. 2001; 285:2859-2863)

(Editor's Note: This work was supported by grants from the Public Health Service. Co-author Jane Cauley, Dr.P.H., receives research support from Merck & Co., Wyeth-Ayerst Research, Eli Lilly & Co., and Roche Pharmaceuticals and has received honoraria from Eli Lilly & Co., Merck & Co., and Procter & Gamble.)

In an accompanying editorial, Katrina Armstrong, M.D., M.Sc., of the University of Pennsylvania School of Medicine, writes:

"Larger studies are needed to provide more power to measure even small associations and reduce the rate of false-negative results. "Pooling data from smaller studies should be done to provide both a more precise estimate of the effect and some insight into the factors that may have led the effect size to differ between studies."

"Given the tremendous potential of genetic epidemiology to elucidate the complex and multi-factorial nature of breast cancer," she adds, "it is important to continue to improve the ability to both conduct and interpret genetic epidemiological studies of cancer risk.

"Only then will it be possible to see clearly the cards women were dealt and to understand how those combinations affect their risk of developing breast cancer." (JAMA. 2001; 285:2907-2909)

13-Jun-2001