Enhanced Susceptibility to Breast Cancer in Korean Women With Elevated Serum Gamma-Glutamyltransferase Levels: A Nationwide Population-Based Cohort Study

Abstract

BackgroundThe incidence of breast cancer has been gradually increasing in Korea. Recently, the elevated level of serum gamma-glutamyltransferase (GGT) has emerged to be associated with the development and progression of some malignancies. This study aimed to determine the effect of serum GGT levels on the risk of developing breast cancer in Korean women.MethodsWe used National Health Insurance Service Health Checkup data to examine the association between serum GGT levels and breast cancer development in Korean women. Women aged 40 years or older who participated in the Korean National Health Screening Examination between January 2009 and December 2009 and who did not develop any cancer within 1-year post examination were included in this analysis (n = 3,109,506). Cox proportional hazard regression analysis was conducted to calculate hazard ratios (HRs) with 95% confidence intervals (CIs).ResultsOverall, an elevated serum GGT level was associated with the increased risk of developing breast cancer; compared to the Q1 group, the Q4 group showed a significantly increased breast cancer risk (HR: 1.120,95% CI: 1.08–1.162). Such a relationship was stronger in post-menopausal women than pre-menopausal women (HR: 1.173, 95% CI: 1.107–1.243; HR: 1.070, 95% CI:1.019–1.124). Women with a high GGT level (Q4) were also at an increased risk of developing carcinoma in situ (CIS) (HR: 1.114, 95% CI: 1.04–1.192). In post-menopausal women, the Q4 group also exhibited higher CIS risk (HR: 1.266, 95% CI: 1.132–1.416). However, no significant difference in the risk of developing CIS was observed between the Q1 and Q4 groups in pre-menopausal women. Further analysis revealed that obese, post-menopausal women with a high GGT level (Q4) were associated with an increased risk of developing breast cancer (HR: 1.214, 95% CI: 1.125–1.31) and CIS (HR: 1.348, 95% CI: 1.159–1.569).ConclusionsOur study results demonstrate that increased serum GGT level is a risk factor for developing breast cancer. The post-menopausal women group with obesity and elevated serum GGT level showed the highest incidence of breast cancer. Thus, serum GGT concentration could be a novel and potential risk factor for breast cancer. Further validation in different ethnic groups would be warranted.

Higher gamma-glutamyl transferase levels are associated with an increased risk of incident systemic sclerosis: a nationwide population-based study

“…The upper normal limit of GGT level in Korea is 63 IU/L for males, and 35 IU/L for females 29 , 30 . In our study, the cut-off of Q4 levels of GGT was ≥ 49 IU/L for males, and ≥ 22 IU/L for females, which are lower than the upper normal limits.…”

Gamma-glutamyl transferase and risk of all-cause and disease-specific mortality: a nationwide cohort study

“…Although studies have reported that GGT expression is increased in various cancers 2 , 22 and its pro-oxidant activity might promote tumor progression by modulating cell proliferation and apoptosis 23 , it is uncertain whether GGT has causal roles in tumor biology or is merely an epiphenomenon associated with carcinogenesis. However, several studies have demonstrated that GGT positively correlated with the development of various cancers including breast, lung, endometrium, gastrointestinal tract, and liver 24 – 28 . Similarly, our analyses showed GGT to be positively associated with overall cancer mortality.…”

Gamma-glutamyl transferase and risk of all-cause and disease-specific mortality: a nationwide cohort study

“…However, several studies have demonstrated that GGT positively correlated with the development of various cancers including breast, lung, endometrium, gastrointestinal tract, and liver [22][23][24][25][26] . Similarly, our analyses showed GGT to be positively associated with overall cancer mortality.…”