Association of endometrial cancer risk with a functional polymorphism (Asp327Asn) in the sex hormone‐binding globulin gene

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Abstract
BACKGROUND: Sex steroid hormones play a central role in the development of endometrial cancer. Sex hormone‐binding globulin (SHBG) modulates the bioavailability of circulating sex hormones and regulates their signaling systems in target cells. Epidemiologic studies have demonstrated that blood SHBG levels are associated inversely with the risk of endometrial cancer. A functional polymorphism, an amino acid substitution of asparagine (Asp) for aspartic acid (Asn) at residue 327 (Asp327Asn) (reference sequence 6259), in the SHBG gene recently was identified and has been associated with an increased half‐life and elevated blood levels of SHBG. The authors tested the hypothesis that this genetic variance is associated with a reduced risk of endometrial cancer in the Shanghai Endometrial Cancer Study, a population‐based, case‐control study that was conducted in urban Shanghai, China between 1997 and 2003.METHODS: This study included 1037 women with newly diagnosed endometrial cancer ages 30 years and 69 years and 1031 age‐matched controls from the community who had completed an in‐person interview and donated a blood and/or buccal cell sample to the study. Genotyping for the Asp327Asn polymorphism was performed by using the TaqMan method. Odds ratio (ORs) and 95% confidence intervals (95% CIs) derived from logistic regression models were used to evaluate the association between the genetic variation and endometrial cancer risk.RESULTS: The allele frequencies of Asn were 15.0% in cases and 17.1% in controls (P = .06). The variant Asn327 allele was associated with a reduced risk of endometrial cancer in postmenopausal women (OR, 0.72; 95% CI, 0.55–0.93) but not in premenopausal women (OR, 1.02; 95% CI, 0.74–1.42). The inverse association was more pronounced among postmenopausal women who had a low body mass index (OR, 0.48; 95% CI, 0.31–0.76) or longer years of menstruation (OR, 0.64; 95% CI, 0.46–0.89), although the results from tests for multiplicative interaction were not statistically significant.CONCLUSIONS: The current results suggested that the codon 327 Asn allele in the SHBG gene may be related to a reduced risk of endometrial cancer among postmenopausal women. Cancer 2007. © 2007 American Cancer Society.

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