Special Issue “Gynaecological Cancers Risk: Breast Cancer, Ovarian Cancer and Endometrial Cancer”

Over the last decade there have been significant advances and developments in our understanding of factors affecting women’s cancer risk, our ability to identify individuals at increased risk and risk stratify populations, as well as implement and evaluate strategies for screening and prevention [...]

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The association between XRCC3 rs1799794 polymorphism and cancer risk: a meta-analysis of 34 case–control studies

BMC Medical Genomics ◽

10.1186/s12920-021-00965-4 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Weiqing Liu ◽

Shumin Ma ◽

Lei Liang ◽

Zhiyong Kou ◽

Hongbin Zhang ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Thyroid Cancer ◽

Cancer Risk ◽

Large Scale ◽

Meta Analysis ◽

Cochrane Library ◽

Cancer Type ◽

Increased Risk ◽

Risk Of Cancer

Abstract Background Studies on the XRCC3 rs1799794 polymorphism show that this polymorphism is involved in a variety of cancers, but its specific relationships or effects are not consistent. The purpose of this meta-analysis was to investigate the association between rs1799794 polymorphism and susceptibility to cancer. Methods PubMed, Embase, the Cochrane Library, Web of Science, and Scopus were searched for eligible studies through June 11, 2019. All analyses were performed with Stata 14.0. Subgroup analyses were performed by cancer type, ethnicity, source of control, and detection method. A total of 37 studies with 23,537 cases and 30,649 controls were included in this meta-analysis. Results XRCC3 rs1799794 increased cancer risk in the dominant model and heterozygous model (GG + AG vs. AA: odds ratio [OR] = 1.04, 95% confidence interval [CI] = 1.00–1.08, P = 0.051; AG vs. AA: OR = 1.05, 95% CI = 1.00–1.01, P = 0.015). The existence of rs1799794 increased the risk of breast cancer and thyroid cancer, but reduced the risk of ovarian cancer. In addition, rs1799794 increased the risk of cancer in the Caucasian population. Conclusion This meta-analysis confirms that XRCC3 rs1799794 is related to cancer risk, especially increased risk for breast cancer and thyroid cancer and reduced risk for ovarian cancer. However, well-designed large-scale studies are required to further evaluate the results.

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THE RISK OF DEVELOPING GYNECOLOGICAL CANCER IN WOMEN AFTER AN IN VITRO FERTILIZATION PROGRAM

"Medical & pharmaceutical journal "Pulse" ◽

10.26787/nydha-2686-6838-2021-23-9-7-13 ◽

2021 ◽

pp. 7-13

Author(s):

Allakhyarov D.Z. ◽

Petrov Yu.A. ◽

Palieva N.V.

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Endometrial Cancer ◽

In Vitro Fertilization ◽

Gynecological Cancer ◽

The Body ◽

Fertilization Program ◽

Vitro Fertilization ◽

Increased Risk

This article presents reviews of literature sources on the issue of assessing the risk of developing gynecological cancer in women after an in vitro fertilization program. Infertility and infertile marriages have now become quite a big problem of modern medicine. Against the background of the unfavorable demographic situation in the Russian Federation, this problem is becoming quite urgent. The main way to solve this situation is assisted reproductive technologies, among which the most common is in vitro fertilization. The in vitro fertilization program is accompanied by a hormonal ovulation stimulation procedure to obtain a female germ cell capable of fertilization. Against the background of the active use of the in vitro fertilization procedure, many patients had concerns related to the risk of developing gynecological cancer after the IVF procedure, which is due to the use of hormonal drugs to stimulate the ovaries. Also of concern is the fact that certain types of cancer, including ovarian cancer, endometrial cancer and breast cancer, are hormone-dependent. In this regard, multiple large-scale studies were conducted, which showed that the risk of developing gynecological cancer is really increased in patients after the in vitro fertilization program. In particular, breast cancer in women after the in vitro fertilization program is more common by 10%, and in women without a history of pregnancy and over the age of 40, it is more common by 31%. The increased risk may be due to age-related vulnerability to the effects of hormones or higher doses of hormones during the IVF procedure. Ovarian cancer and endometrial cancer are also more common in patients after IVF. According to the research results, it is suggested that it is not the IVF procedure itself that causes the development of cancer, but excessive hormonal load of the body, which leads to the launch of carcinogenesis.

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The association between XRCC3 rs1799794 polymorphism and cancer risk: a meta-analysis of 34 case-control studies

10.21203/rs.3.rs-454818/v1 ◽

2021 ◽

Author(s):

Weiqing Liu ◽

Shumin Ma ◽

Lei Liang ◽

Zhiyong Kou ◽

Hongbin Zhang ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Thyroid Cancer ◽

Cancer Risk ◽

Large Scale ◽

Meta Analysis ◽

Cochrane Library ◽

Cancer Type ◽

Increased Risk ◽

Risk Of Cancer

Abstract Background: Studies on the XRCC3 rs1799794 polymorphism show that this polymorphism is involved in a variety of cancers, but its specific relationships or effects are not consistent. The purpose of this meta-analysis was to investigate the association between rs1799794 polymorphism and susceptibility to cancer. Methods: PubMed, Embase, the Cochrane Library, Web of Science, and Scopus were searched for eligible studies through June 11, 2019. All analyses were performed with Stata 14.0. Subgroup analyses were performed by cancer type, ethnicity, source of control, and detection method. A total of 37 studies with 23,537 cases and 30,649 controls were included in this meta-analysis. Results: XRCC3 rs1799794 increased cancer risk in the dominant model and heterozygous model (GG+AG vs. AA: odds ratio [OR] = 1.04, 95% confidence interval [CI] = 1.00–1.08, P = 0.051; AG vs. AA: OR = 1.05, 95% CI = 1.00–1.01, P = 0.015). The existence of rs1799794 increased the risk of breast cancer and thyroid cancer, but reduced the risk of ovarian cancer. In addition, rs1799794 increased the risk of cancer in the Caucasian population. Conclusion: This meta-analysis confirms that XRCC3 rs1799794 is related to cancer risk, especially increased risk for breast cancer and thyroid cancer and reduced risk for ovarian cancer. However, well-designed large-scale studies are required to further evaluate the results.

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Prescribing tamoxifen in primary care for the prevention of breast cancer: a national online survey of GPs’ attitudes

British Journal of General Practice ◽

10.3399/bjgp17x689377 ◽

2017 ◽

Vol 67 (659) ◽

pp. e414-e427 ◽

Cited By ~ 21

Author(s):

Samuel G Smith ◽

Robbie Foy ◽

Jennifer A McGowan ◽

Lindsay C Kobayashi ◽

Andrea DeCensi ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Secondary Care ◽

Online Survey ◽

Preventive Therapy ◽

Factors Affecting ◽

Nice Guideline ◽

Increased Risk ◽

Reduce Breast Cancer Risk

BackgroundThe cancer strategy for England (2015–2020) recommends GPs prescribe tamoxifen for breast cancer primary prevention among women at increased risk.AimTo investigate GPs’ attitudes towards prescribing tamoxifen.Design and settingIn an online survey, GPs in England, Northern Ireland, and Wales (n = 928) were randomised using a 2 × 2 between-subjects design to read one of four vignettes describing a healthy patient seeking a tamoxifen prescription.MethodIn the vignette, the hypothetical patient’s breast cancer risk (moderate versus high) and the clinician initiating the prescription (GP prescriber versus secondary care clinician [SCC] prescriber) were manipulated in a 1:1:1:1 ratio. Outcomes were willingness to prescribe, comfort discussing harms and benefits, comfort managing the patient, factors affecting the prescribing decision, and awareness of tamoxifen and the National Institute for Health and Care Excellence (NICE) guideline CG164.ResultsHalf (51.7%) of the GPs knew tamoxifen can reduce breast cancer risk, and one-quarter (24.1%) were aware of NICE guideline CG164. Responders asked to initiate prescribing (GP prescriber) were less willing to prescribe tamoxifen than those continuing a prescription initiated in secondary care (SCC prescriber) (68.9% versus 84.6%, P<0.001). The GP prescribers reported less comfort discussing tamoxifen (53.4% versus 62.5%, P = 0.01). GPs willing to prescribe were more likely to be aware of the NICE guideline (P = 0.039) and to have acknowledged the benefits of tamoxifen (P<0.001), and were less likely to have considered its off-licence status (P<0.001).ConclusionInitiating tamoxifen prescriptions for preventive therapy in secondary care before asking GPs to continue the patient’s care may overcome some prescribing barriers.

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Women’s health behaviour change after receiving breast cancer risk estimates with tailored screening and prevention recommendations

BMC Cancer ◽

10.1186/s12885-022-09174-3 ◽

2022 ◽

Vol 22 (1) ◽

Author(s):

Linda Rainey ◽

Daniëlle van der Waal ◽

Louise S. Donnelly ◽

Jake Southworth ◽

David P. French ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Risk Communication ◽

Personal Characteristics ◽

Degree Relative ◽

Increased Risk ◽

Screening And Prevention ◽

Secondary Breast Cancer ◽

Risk Of Cancer

Abstract Background The Predicting Risk of Cancer at Screening (PROCAS) study provided women who were eligible for breast cancer screening in Greater Manchester (United Kingdom) with their 10-year risk of breast cancer, i.e., low (≤1.5%), average (1.5–4.99%), moderate (5.-7.99%) or high (≥8%). The aim of this study is to explore which factors were associated with women’s uptake of screening and prevention recommendations. Additionally, we evaluated women’s organisational preferences regarding tailored screening. Methods A total of 325 women with a self-reported low (n = 60), average (n = 125), moderate (n = 80), or high (n = 60) risk completed a two-part web-based survey. The first part contained questions about personal characteristics. For the second part women were asked about uptake of early detection and preventive behaviours after breast cancer risk communication. Additional questions were posed to explore preferences regarding the organisation of risk-stratified screening and prevention. We performed exploratory univariable and multivariable regression analyses to assess which factors were associated with uptake of primary and secondary breast cancer preventive behaviours, stratified by breast cancer risk. Organisational preferences are presented using descriptive statistics. Results Self-reported breast cancer risk predicted uptake of (a) supplemental screening and breast self-examination, (b) risk-reducing medication and (c) preventive lifestyle behaviours. Further predictors were (a) having a first degree relative with breast cancer, (b) higher age, and (c) higher body mass index (BMI). Women’s organisational preferences for tailored screening emphasised a desire for more intensive screening for women at increased risk by further shortening the screening interval and moving the starting age forward. Conclusions Breast cancer risk communication predicts the uptake of key tailored primary and secondary preventive behaviours. Effective communication of breast cancer risk information is essential to optimise the population-wide impact of tailored screening.

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Gastrointestinal cancer risk in Irish hereditary breast ovarian cancer families.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.4_suppl.413 ◽

2013 ◽

Vol 31 (4_suppl) ◽

pp. 413-413

Author(s):

Darragh S Gogarty ◽

Tomas Lyons ◽

Michael P. Farrell ◽

Naoise Maria Dorman ◽

Andrew J Green ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Cancer Risk ◽

Lynch Syndrome ◽

Early Onset ◽

Carrier Status ◽

Hereditary Breast Ovarian Cancer ◽

Mutation Carriers ◽

Increased Risk ◽

Age Of Diagnosis

413 Background: Colorectal and breast cancer are linked in certain predisposition syndromes such as Cowden and Peutz-Jegers syndrome. Breast cancer risk also appears increased in certain Lynch syndrome kindreds. Original reports suggested an increased risk of colorectal malignancies in BRCA1/2 mutation carriers. Two large studies in Ashkenazi Jewish populations subsequently contradicted this early evidence, although neither study was powered to address effects if each gene independently, or other modifier effects in certain families. We report the Irish experience of colorectal and gastro-esophageal (GE) cancer in hereditary breast ovarian cancer (HBOC) families. Methods: 97 HBOC families at two tertiary referral centres were reviewed for the presence of early onset GE malignancies. The medical records of individuals with GE cancer were reviewed to determine carrier status. Clinical data including age of diagnosis, stage, treatment and outcome were extracted. Median age of diagnosis and outcome were compared among BRCA1/2 mutation carriers and non-carriers. Results: We identified 30 individuals with GE malignancies in 97 HBOC families (19 with colorectal, 11 with gastric). Two families were excluded as Lynch syndrome was also diagnosed in these families. Definitive carrier status was available on 8 individuals. Additional 7 individuals were obligate carriers. Age at diagnosis ranged from 27-84 years (median=60). Median age of CRC diagnosis among carriers was 54 compared with 61 among non-carriers (p=0.20). Median age of gastric diagnosis among carriers was 66 compared with 53 among non-carriers. Conclusions: Early onset colorectal cancer occurs in certain HBOC families and may be related to mutation status. No genotype-phenotype association was identified in this study. An additional 150 Irish HBOC families are being screened for early onset GI malignancies and updated data will be presented at the meeting.

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Serum Estradiol and 20 Site-Specific Cancers in Women: Mendelian Randomization Study

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab713 ◽

2021 ◽

Author(s):

Susanna C Larsson ◽

Siddhartha Kar ◽

John R B Perry ◽

Paul Carter ◽

Mathew Vithayathil ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Estrogen Receptor ◽

Endometrial Cancer ◽

Mendelian Randomization ◽

Site Specific ◽

Increased Risk ◽

Estrogen Receptor Positive ◽

Positive Breast Cancer

Abstract Context The causal role of endogenous estradiol in cancers other than breast and endometrial cancer remains unclear. Objective To assess the causal associations of endogenous 17β-estradiol (E2), the most potent estrogen, with cancer risk in women through Mendelian randomization. Methods As primary genetic instrument, we used a genetic variant in the CYP19A1 gene that is strongly associated with serum E2 levels. Summary statistics genetic data for the association of the E2 variant with breast, endometrial, and ovarian cancer were obtained from large-scale consortia. We additionally estimated the associations of the E2 variant with any and 20 site-specific cancers in 198 825 women of European descent in UK Biobank. Odds ratios (OR) of cancer per 0.01 unit increase in log-transformed serum E2 levels in pmol/L were estimated using the Wald ratio. Results Genetic predisposition to higher serum E2 levels was associated with increased risk of estrogen receptor positive breast cancer (OR 1.02; 95% confidence interval [CI] 1.01-1.03; P=2.5×10 -3), endometrial cancer overall (OR 1.09; 95% CI 1.06-1.11; P=7.3×10 -13), and endometrial cancer of the endometrioid histology subtype (OR 1.10; 95% CI 1.07-1.13; P=2.1×10 -11). There were suggestive associations with breast cancer overall (OR 1.01; 95% CI 1.00-1.02; P=0.02), ovarian cancer of the endometrioid subtype (OR 1.05; 95% CI 1.01-1.10; P=0.02), and stomach cancer (OR 1.12; 95% CI 1.00-1.26; P=0.05), but no significant association with other cancers. Conclusion This study supports a role of E2 in the development of estrogen receptor positive breast cancer and endometrioid endometrial cancer, but found no strong association with other cancers in women.

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Endometrial Cancer Incidence in Endometriosis and Adenomyosis

Cancers ◽

10.3390/cancers13184592 ◽

2021 ◽

Vol 13 (18) ◽

pp. 4592

Author(s):

Marjolein Hermens ◽

Anne M. van Altena ◽

Iris Velthuis ◽

Danielle C. M. van de Laar ◽

Johan Bulten ◽

...

Keyword(s):

Ovarian Cancer ◽

Endometrial Cancer ◽

Cohort Study ◽

Cancer Risk ◽

Retrospective Cohort ◽

Population Based ◽

First Year ◽

Endometrial Cancer Risk ◽

Increased Risk

Women with histologically proven endometriosis/adenomyosis have an increased risk of ovarian cancer. Small studies show conflicting results on the endometrial cancer risk in women with endometriosis/adenomyosis. Therefore, we assessed the incidence of endometrial cancer in women with histologically proven endometriosis or adenomyosis. We performed a population-based retrospective cohort study of 129,862 women with histologically proven endometriosis/adenomyosis, matched with 132,700 women with a nevus selected from the Dutch pathology registry between 1990 and 2015. Histology results for endometrial cancer were retrieved. Crude and age-adjusted odds ratios for endometrial cancer were estimated. In the endometriosis/adenomyosis group, 1827 (1.4%) women had a histological report on endometrial cancer, and in the nevus group, 771 (0.6%) women. The age-adjusted OR for endometrial cancer was 2.58 (95%CI 2.37–2.81). After excluding the first year of follow-up, the age-adjusted OR was 0.76 (95%CI 0.63–0.92), indicating that endometrial cancer is most often found at time of histological diagnosis of endometriosis/adenomyosis. In around 20% of the endometrial cancer cases, the endometrial cancer was not recognized until after hysterectomy. Of these women, 35% had no prior (micro)curettage or biopsy. This study shows an increased incidence of endometrial cancer in women with histologically proven endometriosis and adenomyosis.

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CDK5RAP3, a New BRCA2 Partner That Regulates DNA Repair, Is Associated with Breast Cancer Survival

Cancers ◽

10.3390/cancers14020353 ◽

2022 ◽

Vol 14 (2) ◽

pp. 353

Author(s):

Jordi Minguillón ◽

María José Ramírez ◽

Llorenç Rovirosa ◽

Pilar Bustamante-Madrid ◽

Cristina Camps-Fajol ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Dna Damage ◽

Dna Repair ◽

Homologous Recombination ◽

Cancer Risk ◽

Brca2 Mutation ◽

Ovarian Cancer Risk ◽

Breast And Ovarian Cancer ◽

Increased Risk

BRCA2 is essential for homologous recombination DNA repair. BRCA2 mutations lead to genome instability and increased risk of breast and ovarian cancer. Similarly, mutations in BRCA2-interacting proteins are also known to modulate sensitivity to DNA damage agents and are established cancer risk factors. Here we identify the tumor suppressor CDK5RAP3 as a novel BRCA2 helical domain-interacting protein. CDK5RAP3 depletion induced DNA damage resistance, homologous recombination and single-strand annealing upregulation, and reduced spontaneous and DNA damage-induced genomic instability, suggesting that CDK5RAP3 negatively regulates double-strand break repair in the S-phase. Consistent with this cellular phenotype, analysis of transcriptomic data revealed an association between low CDK5RAP3 tumor expression and poor survival of breast cancer patients. Finally, we identified common genetic variations in the CDK5RAP3 locus as potentially associated with breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. Our results uncover CDK5RAP3 as a critical player in DNA repair and breast cancer outcomes.

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MNGI-12. PLEIOTROPIC MLLT10 VARIATION CONFERS RISK OF MENINGIOMA, BREAST, AND OVARIAN CANCERS

Neuro-Oncology ◽

10.1093/neuonc/noz175.594 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi142-vi142

Author(s):

Kyle Walsh ◽

Chenan Zhang ◽

Lisa Calvocoressi ◽

Helen Hansen ◽

Andrew Berchuck ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Cancer Risk ◽

Risk Allele ◽

Meta Analysis ◽

Ovarian Cancer Risk ◽

Genome Wide Association Studies ◽

Ovarian Cancers ◽

Genome Wide ◽

Increased Risk

Abstract BACKGROUND Women ages 35–44 have three-fold higher risk of meningioma compared to men. Epidemiologic studies have implicated exogenous hormone use, but endogenous hormonal factors are inconsistently associated. Elevated body mass index (BMI) is consistently associated with meningioma risk in both men and women, and personal history of breast cancer has also been associated with meningioma risk. Recent genome-wide association studies (GWAS) have identified a meningioma risk locus on chromosome 10p12 near previous GWAS hits for breast and ovarian cancers. METHODS To elucidate the pleiotropic role of 10p12 variation in predisposition to diverse tumors - possibly via a common mediating factor - we performed imputation‐based fine‐mapping in three case-control datasets of meningioma (927 cases, 790 controls), female breast cancer (28108 cases, 22209 controls), and ovarian cancer (25509 cases, 40941 controls). Analyses were stratified by sex (meningioma), estrogen receptor status (breast), and histotype (ovarian), then combined using ASSET meta-analysis. Lead variants were queried for association with >700 additional traits to identify potential effect-mediators. RESULTS Two-sided ASSET meta-analysis identified a lead variant near the MLLT10 promoter (P=1.4x10-13) associated with significantly increased risk of meningioma in women (OR=1.42, 95% CI: 1.20–1.69) and non-significantly increased risk in men (OR=1.19, 95% CI: 0.91–1.57). The meningioma risk allele was also associated with ovarian cancer risk (OR=1.09, 95% CI: 1.06–1.12) and ER+ breast cancer risk (OR=1.05, 95% CI: 1.02–1.08), but protected against ER- breast cancer (OR=0.91, 95% CI: 0.86–0.96). The risk allele was associated with higher body fat percentage, waist circumference and BMI at genome-wide levels (P< 5.0x10-8), but mediation analysis adjusting for BMI did not attenuate its association with meningioma risk. CONCLUSION We identify a MLLT10 eQTL that confers risk of female meningioma, ER+ breast cancer, ovarian cancer, and obesity, but which protects against ER- breast cancer. Our results implicate a possible estrogenic mechanism underlying meningioma tumorigenesis.

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