Older White Women With Specific Genetic Variation Are At Increased Risk.(variation in gene for transforming growth factor beta-1 increases risk of breast cancer)

2001 JUL 5 - (NewsRx Network) -- Variations in a gene known as transforming growth factor [beta]-1 (TGF-[beta]-1) appear to be associated with risk of breast cancer among older white women, according to an article in the June 13. 2001. issue of the Journal of the American Medical Association.

Elad Ziv. MD. 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.

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 a wide variety of tissues. According to background information cited in the article, evidence suggests 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.

To determine if there is an association between variations in the TGF-[beta]-1 gene and the risk of breast cancer. Ziv's team 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%; 48.6% of the women had the T/C genotype; and 36.7% 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 reported.

"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 TIC ...