Risk-Association of CYP11A1 Polymorphisms and Breast Cancer Among Han Chinese Women in Southern China

Sun, Ming; Yang, Xu; Ye, Changsheng; Xu, Weiwen; Yao, Guangyu; Li, Ming

doi:10.3390/ijms13044896

Cited by 10 publications

(12 citation statements)

References 28 publications

(29 reference statements)

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“…Genetic variants may alter CYP11A1 expression or activity, determining sex steroid hormone levels responsible for quantitative phenotypes that include hormone-related disorders. Supporting these hypotheses, other polymorphic variants in this gene have been previously associated with breast and endometrial (Terry et al 2010) cancer susceptibility (Zheng et al 2004, Sun et al 2012 and polycystic ovary syndrome (Gao et al 2010).…”

Section: Discussionmentioning

confidence: 62%

CYP11A1 expression in bone is associated with aromatase inhibitor-related bone loss

Rodríguez-Sanz

Garcia-Giralt

Prieto-Alhambra

et al. 2015

Journal of Molecular Endocrinology

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Aromatase inhibitors (AIs) used as adjuvant therapy in postmenopausal women with hormone receptor-positive breast cancer cause diverse musculoskeletal side effects that include bone loss and its associated fracture. About half of the 391 patients treated with AIs in the Barcelona-Aromatase induced bone loss in early breast cancer cohort suffered a significant bone loss at lumbar spine (LS) and/or femoral neck (FN) after 2 years on AI-treatment. In contrast, up to one-third (19.6% LS, 38.6% FN) showed no decline or even increased bone density. The present study aimed to determine the genetic basis for this variability. SNPs in candidate genes involved in vitamin D and estrogen hormone-response pathways (CYP11A1, CYP17A1, HSD3B2, HSD17B3, CYP19A1, CYP2C19, CYP2C9, ESR1, DHCR7, GC, CYP2R1, CYP27B1, VDR and CYP24A1) were genotyped for association analysis with AI-related bone loss (AIBL). After multiple testing correction, 3 tag-SNPs (rs4077581, s11632698 and rs900798) located in the CYP11A1 gene were significantly associated (P!0.005) with FN AIBL at 2 years of treatment. Next, CYP11A1 expression in human fresh bone tissue and primary osteoblasts was demonstrated by RT-PCR. Both common isoforms of human cholesterol side-chain cleavage enzyme (encoded by CYP11A1 gene) were detected in osteoblasts by western blot. In conclusion, the genetic association of CYP11A1 gene with AIBL and its expression in bone tissue reveals a potential local function of this enzyme in bone metabolism regulation, offering a new vision of the steroidogenic ability of this tissue and new understanding of AI-induced bone loss. Journal of Molecular EndocrinologyResearch M RODRI´GUEZ-SANZ and others CYP11A1 is associated with AI-related bone loss 55:1 69-79http://jme.endocrinology-journals.org Ñ 2015 Society for Endocrinology DOI: 10.1530/JME-15-0079Printed in Great BritainPublished by Bioscientifica Ltd. IntroductionAromatase inhibitors (AIs) are commonly used as adjuvant therapy in postmenopausal women with hormone receptor-positive breast cancer. Although AIs are generally well tolerated with few serious adverse events, a number of musculoskeletal side effects affecting quality of life have been noted and often lead to discontinuation of therapy (Eastell et al. 2006, Henry et al. 2008.The most common side effects reported with AIs are exacerbation of menopausal symptoms as a result of low estrogen levels; these include pain syndromes, bone loss and associated fracture , Laroche et al. 2014. Several prospective studies and clinical trials have noted the need for assessment and treatment of these musculoskeletal adverse events (Reid et al. 2008, Brufsky et al. 2009, Servitja et al. 2012. In particular, bone mineral density (BMD) reduction and fracture incidence associated with AI therapy can be significantly reduced by oral bisphosphonates (BP) treatment (Bouvard et al. 2014).We are currently conducting a prospective, nonselected, observational, clinical cohort study (BarcelonaAromatase induced bone loss in early breast cancer (B-ABLE...

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Section: Discussionmentioning

confidence: 62%

CYP11A1 expression in bone is associated with aromatase inhibitor-related bone loss

Rodríguez-Sanz

Garcia-Giralt

Prieto-Alhambra

et al. 2015

Journal of Molecular Endocrinology

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“…Both CYP11A1 SNPs are in the intronic region of the gene and there is no information available about their functionality. The variant allele of rs2959008 was associated with a decreased breast cancer risk in Han Chinese [ 30 ]. There is no literature on rs7173655 and breast cancer risk but the variant allele was associated with an increased endometrial cancer risk [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Interaction between dietary acrylamide intake and genetic variants for estrogen receptor-positive breast cancer risk

et al. 2018

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Purpose The association between dietary acrylamide intake and estrogen receptor-positive (ER+) breast cancer risk in epidemiological studies is inconsistent. By analyzing gene-acrylamide interactions for ER+ breast cancer risk, we aimed to clarify the role of acrylamide intake in ER+ breast cancer etiology. Methods The prospective Netherlands Cohort Study on diet and cancer includes 62,573 women, aged 55-69 years. At baseline, a random subcohort of 2589 women was sampled from the total cohort for a case-cohort analysis approach. Dietary acrylamide intake of subcohort members (n = 1449) and ER+ breast cancer cases (n = 844) was assessed with a food frequency questionnaire. We genotyped single nucleotide polymorphisms (SNPs) in genes in acrylamide metabolism, sex steroid systems, oxidative stress and DNA repair. Multiplicative interaction between acrylamide intake and SNPs was assessed with Cox proportional hazards analysis, based on 20.3 years of follow-up. Results Unexpectedly, there was a statistically non-significant inverse association between acrylamide and ER+ breast cancer risk among all women but with no clear dose-response relationship, and no association among never smokers. Among the results for 57 SNPs and 2 gene deletions, rs1056827 in CYP1B1, rs2959008 and rs7173655 in CYP11A1, the GSTT1 gene deletion, and rs1052133 in hOGG1 showed a statistically significant interaction with acrylamide intake for ER+ breast cancer risk. Conclusions This study did not provide evidence for a positive association between acrylamide intake and ER+ breast cancer risk. If anything, acrylamide was associated with a decreased ER+ breast cancer risk. The interaction with SNPs in CYP1B1 and CYP11A1 suggests that acrylamide may influence ER+ breast cancer risk through sex hormone pathways.

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“…Laboratory protocols for the DNA extraction and genotyping methods used by the SCBCGS have been previously described in detail [ 18 , 19 ]. Briefly, genomic DNA was extracted from whole blood using TIANamp Genomic DNA Purification Kit according to the manufacturer's protocol and stored at −80°C until used for further analysis.…”

Section: Methodsmentioning

confidence: 99%

“…Thus, only 5 SNPs (rs1078806, rs1219648, rs2420946, rs2981579, and rs2981582) were selected for analysis in this study. The genotyping of SNPs was done using the SEQUENOM MassARRAY matrix-assisted laser desorption ionization time of flight mass spectrometry platform [ 18 , 19 ].…”

Section: Methodsmentioning

confidence: 99%

Heterogeneity of Breast Cancer Associations with Common Genetic Variants inFGFR2according to the Intrinsic Subtypes in Southern Han Chinese Women

Lee

Yang

Chen

et al. 2015

BioMed Research International

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GWAS have identified variation in the FGFR2 locus as risk factors for breast cancer. Validation studies, however, have shown inconsistent results by ethnics and pathological characteristics. To further explore this inconsistency and investigate the associations of FGFR2 variants with breast cancer according to intrinsic subtype (Luminal-A, Luminal-B, ER−&PR−&HER2+, and triple negative) among Southern Han Chinese women, we genotyped rs1078806, rs1219648, rs2420946, rs2981579, and rs2981582 polymorphisms in 609 patients and 882 controls. Significant associations with breast cancer risk were observed for rs2420946, rs2981579, and rs2981582 with OR (95% CI) per risk allele of 1.19 (1.03–1.39), 1.24 (1.07–1.43), and 1.17 (1.01–1.36), respectively. In subtype specific analysis, above three SNPs were significantly associated with increased Luminal-A risk in a dose-dependent manner (P trend < 0.01); however, only rs2981579 was associated with Luminal-B, and none were linked to ER−&PR− subtypes (ER−&PR−&HER2+ and triple negative). Haplotype analyses also identified common haplotypes significantly associated with luminal-like subtypes (Luminal-A and Luminal-B), but not with ER−&PR− subtypes. Our results suggest that associations of FGFR2 SNPs with breast cancer were heterogeneous according to intrinsic subtype. Future studies stratifying patients by their intrinsic subtypes will provide new insights into the complex genetic mechanisms underlying breast cancer.

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Risk-Association of CYP11A1 Polymorphisms and Breast Cancer Among Han Chinese Women in Southern China

Cited by 10 publications

References 28 publications

CYP11A1 expression in bone is associated with aromatase inhibitor-related bone loss

CYP11A1 expression in bone is associated with aromatase inhibitor-related bone loss

Interaction between dietary acrylamide intake and genetic variants for estrogen receptor-positive breast cancer risk

Heterogeneity of Breast Cancer Associations with Common Genetic Variants inFGFR2according to the Intrinsic Subtypes in Southern Han Chinese Women

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