Polymorphism of HSD17B1 Ser312Gly with Cancer Risk: Evidence from 66,147 Subjects

Abstract

Hydroxysteroid (17-beta)dehydrogenase 1(HSD17B1) plays a central role in sex steroid hormone metabolism. HSD17B1 polymorphic variants may contribute to cancer susceptibility. Numerous investigations have been conducted to assess the association between HSD17B1 Ser312Gly polymorphism and cancer risk in multiple ethnicities, yet these have produced inconsistent results. We therefore performed this comprehensive meta-analysis to attempt to provide a quality assessment of the association of interest. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of associations. After a systematic literature search of several major public databases, 20 studies involving 29,460 cases and 36,687 controls were included in this meta-analysis. No significant association was found between HSD17B1 Ser312Gly polymorphism and cancer risk. However, Ser312Gly polymorphism showed a significantly decreased risk for Caucasians (there were 44,284 Caucasians for analysis, comprising 19,889 cases and 24,395 controls) in the subgroup analysis by ethnicity (dominant: OR = 0.958, 95% CI = 0.919-0.998; and allele comparing: OR = 0.973, 95% CI = 0.947-0.999). And there was the same trend towards risk in the population-based (PB) controls (homozygous: OR = 0.951, 95% CI = 0.908-0.997 and allele comparing: OR = 0.976, 95% CI = 0.954-0.999), but not among Asians or hospital-based (HB) controls. In addition, no association was observed in the stratified analysis for breast cancer studies by source of control, ethnicity and quality score. These findings suggested that the HSD17B1 Ser312Gly polymorphism might confer genetic cancer susceptibility in an ethnic-dependent manner, especially among Caucasians. Well-designed, large-scale studies are warranted to validate these findings.

Involvement of 17β-hydroxysteroid dehydrogenase type gene 1 937 A>G polymorphism in infertility in Polish Caucasian women with endometriosis

“…They include development of the risk of endometrial and breast cancer [31, 33–35]. The meta-analysis did not show significant association between HSD17B1 rs605059 gene polymorphisms and risks of endometrial cancer [31].…”

“…The meta-analysis did not show significant association between HSD17B1 rs605059 gene polymorphisms and risks of endometrial cancer [31]. Additionally, the recent meta-analysis conducted by Shi et al (2016) suggested that the HSD17B1 937 G allele may protect from breast cancer development in Caucasians, but not among Asians [35]. …”

Estrogen and androgen-converting enzymes 17β-hydroxysteroid dehydrogenase and their involvement in cancer: with a special focus on 17β-hydroxysteroid dehydrogenase type 1, 2, and breast cancer

“…The impact of HSD17B polymorphisms appears limited. A recent meta-analysis on the impact of HSD17B1 polymorphism rs605059 shows that it might confer genetic cancer susceptibility in Caucasians, but authors propose more studies are needed [77]. On the other hand, the SNP rs4445895_T was shown to be associated with lower intratumoral HSD17B2 mRNA levels and inversely correlated with E2 levels [78], indicating that HSD17B2 polymorphisms may have clinical relevance.…”

Macronutrient intakes and serum oestrogen, and interaction with polymorphisms in CYP19A1 and HSD17B1 genes: a cross-sectional study in postmenopausal Japanese women

“…Polymorphisms in the CYP19A1 gene that encodes aromatase, an enzyme that converts androgens to oestrogens, were shown to be associated with serum sex hormone levels in Japanese people (11)(12)(13) . The rs605059 polymorphism in the HSD17B1 gene that encodes 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1), which catalyses the synthesis of E2 from oestrone (E1), has been investigated regarding its association with multiethnic breast cancer risk (14,15) .…”