CYP17 genetic polymorphism in endometrial cancer: are only steroids involved?

Berstein, Lev M.; Imyanitov, Evgeny N.; Gamajunova, V. B.; Kovalevskij, A. J.; Kuligina, Ekatherina Sh.; Belogubova, Evgeniya V.; Buslov, Konstantin G.; Karpova, Maria B.; Togo, Alexandr V.; Volkov, O N; Коваленко, И. Г.

doi:10.1016/s0304-3835(02)00019-8

Cited by 38 publications

(24 citation statements)

References 24 publications

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“…Of these two enzymes, CYP17 T to C polymorphic variant is implicated in osteoporotic predisposition. Most studies, however, could not establish a relationship between CYP17 TC polymorphism and circulating estrogen-androgen levels (Berstein et al, 2002;Feigelson et al, 2002;Kado et al, 2002;Ye and Parry, 2002;Somner et al, 2004). We also did not observe a statistically significant association between CYP17 TC polymorphism and sex steroid levels; however, there was a tendency of higher testosterone levels in osteoporotic patients compared to controls in the CYP17 TC genotype.…”

Section: Discussioncontrasting

confidence: 83%

Association of serum sex steroid levels and bone mineral density with CYP17 and CYP19 gene polymorphisms in postmenopausal women in Turkey

Yılmaz

Pazarbaşı²,

Güzel³

et al. 2011

Genet. Mol. Res.

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ABSTRACT. Many clinical conditions, including osteoporosis, are associated with serum levels of sex steroids. Enzymes that regulate ratelimiting steps of steroidogenic pathways, such as CYP17 and CYP19, are also regarded as significant factors that may cause the development of these conditions. We investigated the association of two common polymorphisms, in the promoter region (T→C substitution) of CYP17 and exon 3 (G→A) of CYP19, with bone mineral density (BMD) in the lumbar spine and femoral neck and serum androgen/estradiol, in a case-control study of 172 postmenopausal women aged 62.3 ± 9.6 years (mean ± SD). The CYP17 TC genotype was significantly overrepresented in patients compared to controls, and TC genotype neck T-score and lumbar T-score values were significantly higher in patients compared to controls. CYP17 TC and TT genotype testosterone and DHEA-SO 4 levels were lower in patients compared to controls. All three genotypes of CYP19 had almost the same distribution among patients. The CYP19 AG genotype, however, was most frequent among controls. CYP19 lumbar BMD levels were close to each other among the different genotypes; however, AA and AG genotypes were significantly lower in patients. Testosterone and DHEA-SO 4 levels in the CYP19 GG genotype were higher compared to those of the other genotypes in patients but not in controls. CYP19 GA individuals had lower E 2 levels and lower BMD in controls and patients. Femoral neck BMD and lumbar T-score were also diminished with GA transition. In conclusion, CYP17 and CYP19 gene polymorphisms were found to be associated with osteoporosis in postmenopausal women in Turkey.

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Section: Discussioncontrasting

confidence: 83%

Association of serum sex steroid levels and bone mineral density with CYP17 and CYP19 gene polymorphisms in postmenopausal women in Turkey

Yılmaz

Pazarbaşı²,

Güzel³

et al. 2011

Genet. Mol. Res.

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“…Epidemiologic studies of the CYP17 polymorphism in relation to hormonally-related cancers (e.g., breast, endometrium, prostate) have yielded inconsistent results, with reports showing either the A1 or A2 allele being associated with an increased risk. 8,9,[13][14][15][16][17][18][19][20][29][30][31][32][33][34][35] Our observation that A1 is the risk allele for biliary tract cancer in Chinese is not totally unexpected. Some studies conducted in Asia have also reported the A1 allele as the risk allele.…”

Section: Discussionmentioning

confidence: 98%

CYP17 MspA1 polymorphism and risk of biliary tract cancers and gallstones: A population‐based study in Shanghai, China

Hou

Gao

et al. 2006

Intl Journal of Cancer

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Biliary tract cancers, encompassing cancers of the gallbladder, extrahepatic bile duct and ampulla of Vater, are rare but highly fatal malignancies. Other than gallstones, little is known about the risk factors for biliary tract cancers. Endogenous estrogens are thought to play a role in the etiology of gallstones and gallbladder cancer, since both conditions predominate in females and are associated with parity and obesity. In view of reports linking the CYP17 MspA1 polymorphism to high circulating levels of estrogens and a predisposition to other hormonally related cancers, we examined the relationship between CYP17 MspA1 variants and risk of biliary disease in a population-based case-control study in Shanghai. The study included 446 cancer cases (254 gallbladder, 139 extrahepatic bile duct, 53 ampullary cancers), 929 biliary stone cases (691 gallbladder, 238 bile duct) and 818 population controls. Genomic DNA from peripheral blood lymphocytes was used for genotyping. Relative to those with the A2/A2 genotype, A1 carriers (A1/A1 and A1/A2 genotypes) had an increased risk of gallbladder cancer (odds ratio (OR) 5 1.5, 95% confidence interval (CI) 5 1.1-2.1). In addition, women with the A1 allele and high parity (≥3) had a 3-fold risk of gallbladder cancer (OR 5 3.3, 95% CI 5 1.6-6.9), compared to those with the A2/A2 genotype and lower parity, with the highest risk seen for those also having biliary stones (OR 5 4.6, 95% CI 5 1.8-11.7, P interaction 5 0.04). The A1 allele was not associated with a higher risk of gallstones except among those with body mass index (BMI) greater than 25 kg/m 2 (OR 5 3.1, 95% CI 5 2.0-4.8, P interaction 5 0.02) and among those with a history of diabetes (OR 5 2.5, 95% CI 5 1.4-4.3, P interaction 5 0.09). No clear relation was seen between the CYP17 polymorphism and cancers of the bile duct or ampulla of Vater. The association of the CYP17 MspA1 polymorphism with an increased risk of gallbladder cancer, as well as biliary stones among overweight and diabetic individuals, suggests an interplay between genetic and hormonal risk factors in gallbladder disease. ' 2005 Wiley-Liss, Inc.Key words: biliary tract cancers; gallstones; polymorphisms; epidemiology; China Biliary tract cancers, consisting of tumors arising in the gallbladder, extrahepatic bile ducts and ampulla of Vater, are relatively uncommon in most parts of the world, although elevated rates have been reported in certain population groups.1,2 In Shanghai, China, there has been a rapid increase in the incidence of biliary tract cancers, 3 providing a special opportunity for epidemiologic study of these tumors.Cholesterol gallstones represent the main predisposing factor in gallbladder cancer. Although the mechanism underlying this association is unclear, both gallstones and gallbladder cancer predominate in females and are associated with obesity and multiple pregnancies, conditions related to higher levels of estrogens, suggesting that endogenous estrogens are involved in the pathogenesis of these conditions by altering bile...

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“…Although results for these studies were in opposite directions for estrone and estradiol, both studies suggested only small alterations in estrogen levels by genotype that would translate into undetectable changes in endometrial cancer risk, based on observations of the association between endometrial cancer risk and hormones (Kaaks et al 2002;Potischman et al 1996;Zeleniuch-Jacquotte et al 2001). However, other hormonal mechanisms may play a role; for instance, fasting insulin levels were found to be lower for the CC, compared to TT, genotype (P = 0.07) among 114 endometrial cancer cases (Berstein et al 2002).…”

Section: Discussionmentioning

confidence: 99%

“…Three articles were excluded from analysis, as one (Berstein et al 2002) was updated in a later publication (Berstein et al 2004), one (Szyllo et al 2006a) was a duplicate of an included publication (Szyllo et al 2006b), and one (McKean-Cowdin et al 2001) did not provide frequencies for individual genotypes. Study-speciWc crude ORs (95%CI) were calculated from published genotype frequencies of four studies as well as our own.…”

Section: Meta-analysismentioning

confidence: 99%

Genetic variation in CYP17 and endometrial cancer risk

et al. 2008

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Genetic variation in CYP17 is suspected to be related to endometrial cancer risk based on its role in the regulation of steroid and non-steroid hormone biosynthesis. Reported associations between CYP17 and higher levels of estradiol in some studies suggest that the C allele of a T-to-C single nucleotide polymorphism (SNP) in the 5'UTR of CYP17 (rs743572) may be associated with an increased risk of hormone-related cancers. However, five relatively small epidemiologic studies of endometrial cancer have reported that women with the rs743572 C allele have a decreased risk of endometrial cancer. To examine this association, we genotyped rs743572 and eight other haplotype-tagging SNPs (htSNPs), which are estimated to capture >80% of the variation in CYP17 in a population-based study of 497 endometrial cancer cases and 1,024 controls in Poland. Significant associations were not found for rs743572 (per C allele: OR = 1.12, 95%CI 0.96-1.30; P-trend = 0.15), for individual htSNPs, or for extended haplotypes (global P-value = 0.60). When we pooled data from previously published studies with our own (a total of 1,004 endometrial cases and 1,907 controls), we observed significant study heterogeneity in summary estimates of the association between rs743572 and endometrial cancer, as well as evidence of publication bias. In conclusion, our data are not consistent with a decreased endometrial cancer risk associated with rs743572, as previously reported, or with other haplotype-tagging polymorphisms. Further evaluation in consortia is necessary to confirm potential weak associations between common variation in CYP17 and endometrial cancer risk and to address the concern of publication bias.

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CYP17 genetic polymorphism in endometrial cancer: are only steroids involved?

Cited by 38 publications

References 24 publications

Association of serum sex steroid levels and bone mineral density with CYP17 and CYP19 gene polymorphisms in postmenopausal women in Turkey

Association of serum sex steroid levels and bone mineral density with CYP17 and CYP19 gene polymorphisms in postmenopausal women in Turkey

CYP17 MspA1 polymorphism and risk of biliary tract cancers and gallstones: A population‐based study in Shanghai, China

Genetic variation in CYP17 and endometrial cancer risk

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