fitness news
Font size Women’s Health
Glutamyl transferase and breast cancer risk in Guernsey women
– Reported, January 23, 2012
In the Guernsey Breast Cancer Cohort Study, GGT was measured in sera from 1803 normal women. Among these women, 251 subsequently developed cancer, of whom 96 developed breast cancer.
After adjustment for age at entry, height, weight, age at menarche and first birth with nulliparity, there was a highly significant relationship between elevated GGT and breast cancer risk. In the highest quartile, the hazard ratio (HR) was 2.17 (95% confidence interval (CI): 1.19, 3.93). When subdivided by menopausal status, there was a reduced non-significant effect in postmenopausal women, whereas for premenopausal women in the highest quartile, HR was 3.81 (95% CI: 1.37, 10.59). Premenopausal women with serum GGT levels above the normal range had a significantly elevated HR of 4.90 (95% CI: 1.86, 12.94).
These results suggest that premenopausal women with high normal (above median) serum GGT or elevated levels (40IUl-1) are at increased risk of breast cancer and might benefit from close surveillance, possibly with breast magnetic resonance imaging scans. Serum GGT may mark previous exposure to carcinogens and lead to the identification of DNA adducts involved in mammary carcinogenesis.
The Guernsey Cohort Study has been underway since 1961 with the aim of identifying risk factors for breast cancer in a normal population (Wang et al, 2000). In the fourth phase of the study, which recruited volunteers between 1986 and 1990, 4714 women participated, all of whom were aged >32 years and were residents of Guernsey. They attended the Imperial Cancer Research Fund (now Cancer Research, UK) Laboratory in Guernsey and completed a detailed questionnaire with regard to their previous medical and reproductive history.
Follow-up of the cohort is still active and information on cancer incidence is obtained regularly through pathology reports from the only pathology laboratory in Guernsey, as well as from death certificates and data from the South West Cancer Registry. The study was approved by all relevant ethics committees and the women provided written consent.
Postmenopausal women had slightly but significantly higher values than premenopausal women. Thus, in the analyses by menopausal status, the quartiles used are appropriate for each group. GGT was also found to be positively and significantly associated with body mass index and weight in premenopausal women, and with weight in postmenopausal women. It was not found to be significantly associated with parity or age at first birth in either menopausal group.
To determine whether GGT level was related to overall risk of cancer in this cohort, an analysis was conducted on all incident cancers. There were 251 cancers (breast 96, colorectal 21, lung 17, ovary 15, melanoma 14, endometrium 12, lymphoma 8, pancreas 8, oesophagus 7, stomach 4, bladder 4, cervix 4 and kidney 2). Results indicate that, overall, there was a significant increase in risk among those with GGT levels above the normal range. However, when the breast cancer cases were removed from the analysis, no significant relationship was observed between GGT and cancer risk.
his study found a significant relationship between GGT and overall risk of cancer, which disappeared when breast cancer cases were removed from the analysis. After adjustment for known risk factors, including weight, there was an independent significant relationship between elevated GGT and subsequent risk of breast cancer. However, no effect was seen in postmenopausal women, whereas for premenopausal women, HR was 3.82 for the highest quartile. Those premenopausal women with serum GGT levels above the normal range had a significantly elevated HR of 4.90.
A limitation of the study is that we do not have information of alcohol intake among the participants. However, the blood samples were collected between 1986 and 1990 before there was a major increase in alcohol use in women.
Because this was a prospective study, with samples being taken before development of breast cancer, it is likely that GGT elevation was not a result of malignant transformation, but possibly had a role in this process. Although GGT has been implicated in malignancy, this is the first study to show the specific effect in terms of breast cancer risk.
?-Glutamyl transferase catalyses hydrolysis and transpeptidation of extracellular GSH, thereby having a central role in maintaining glutathione homeostasis. GSH is an antioxidant, protecting cells against oxidative stress. Generation of the more reactive glycyl-cysteine reduces ferrous to ferric iron, thereby starting an iron redox cycling process.
It is of particular interest that GGT is associated with increased risk when the woman is premenopausal. In addition, GGT did not seem to be associated with an increased risk for other cancers in this cohort. This raises the possibility of identifying those women with high normal or elevated serum levels. In the absence of evidence of alcohol abuse, these could be selected for closer surveillance. The method of surveillance is still uncertain. Routine clinical examination has not been shown to reduce mortality from breast cancer, nor has mammography in younger women. A recent Consensus Conference on high-risk women, mostly because of their family history, advised that breast magnetic resonance imaging should be performed annually but not before the age of 25 years . If these findings can be replicated in a larger study, they may afford a new and inexpensive opportunity to delineate women who are at high risk of breast cancer with the hope of targeting surveillance, allowing an earlier diagnosis and thereby reducing the mortality accruing from this disease.
Credits:I S Fentiman and D S Allen
More Information: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2905293/?tool=pubmed
– WF Team