Ovarian Cancer In Women Research Articles

Вплив деяких хімічних канцерогенів довкілля на захворюваність гормонозалежними пухлинами та можливі механізми його реалізації (огляд літератури)

Objective: We determined the possible effects of priority chemical environmental carcinogens on the incidence of hormone-dependent tumors and the mechanisms of their effect on the basis of the analysis of literature data and our own research. Results: The performed analysis demonstrates the scanity of the research devoted to the study of chemical carcinogens which are concerned only with the class of polycyclic aromatic hydrocarbons (PAH), benzo(a)pyrene (BP), atmospheric pollution, emissions from vehicles, the cadmium heavy metal and products of smoking containing these substances. The connection with PAH (BP) and the development of breast, ovarian cancer, cadmium with the development of breast, endometrial, ovarian cancer in women and prostate cancer in men was established. Epidemiological data, combined with experimental ones, suggest a possible contribution of carcinogens into the increase of the incidence of hormone-dependent tumors. At the same time, mechanisms of action of PAH and cadmium on the development of hormone-dependent tumors are unclear. The accumulated experimental and epidemiological data allow us to conclude that the oncological danger of these carcinogens lies in the combination of genotoxic and hormone-mimetic properties; the main mechanisms, involved in the realization of the effect of BP and cadmium, are associated with changes and disorders at different levels of the structural and functional organization of the organism, including the endocrine system, which can lead to the development of tumors. The urgency of the problem of the incidence of hormone-dependent tumors and the potential role of the studied chemical carcinogens as pollutants of the environment of human functions indicate the need to take these circumstances into account when developing and implementing preventive measures.

Impact of parity on the incidence of ovarian cancer subtypes: a population-based case–control study

Background Parity is known to have a protective effect as regards ovarian cancer, but its effect on the different histological subtypes of ovarian cancer is not well known. The impact of parity on the incidence of ovarian cancer subtypes was studied. Material and methods All Finnish women diagnosed 1994–2013 with ovarian cancer for the first time were included. Altogether, 5412 cases of ovarian cancer were identified in the Finnish Cancer Registry and stratified according to morphology into serous, mucinous, endometrioid, clear cell and others. Five age-matched controls were randomly selected for each case from the Finnish National Population Registry. Data on postmenopausal hormonal therapy were derived from the Registry of Prescribed drugs and used as cofactors. Multivariate conditional logistic regression for matched case-control data was used to examine the associations between parity parameters and ovarian cancer risk. Results Parous women had lower risk than nulliparous women in getting ovarian cancer of any type under age of 55 years. The odds ratio (OR) for serous cancer was 0.65 (95% confidence interval 0.56–0.77), for mucinous cancer 0.66 (0.52–0.83), for endometrioid cancer 0.52 (0.40–0.68), for clear-cell cancer 0.30 (0.19–0.46) and for other types 0.59 (0.43–0.80). In women aged 55 or older, the respective ORs were 0.86 (0.75–0.99), 0.78 (0.57–1.07), 0.61 (0.47–0.79), 0.44 (0.29–0.66) and 0.74 (0.57–0.95), adjusted for hormone therapy. Number of childbirths was associated with a trend toward reduction of risk, especially in serous and clear-cell cancers. Higher age at first birth was associated with higher risk of clear-cell cancer but otherwise age at first or last birth did not have an impact on the incidence of cancer subtypes. Conclusions Childbirths decrease the risk of all histologic subtypes of epithelial ovarian cancer in women in premenopausal and postmenopausal age.

General population screening for ovarian cancer

Ovarian cancer is the most lethal gynaecological malignancy, in large part because it presents with non-specific symptoms and is often diagnosed at a late stage. 58% of ovarian cancers are metastatic at diagnosis, with a 5-year relative survival of only 30%.1 However, the 5-year relative survival for localised ovarian cancer is 93%.1 This factor has spurred great efforts to develop a screening tool that could allow for earlier detection of ovarian cancer in women who are asymptomatic. The CA125 blood test and transvaginal ultrasound scan (TVS) have been the most promising screening tools to date.

EP551 - Weight gain and the risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers

Background: Weight gain and other anthropometric measures on the risk of ovarian cancer for women with BRCA mutations are not known. We conducted a prospective analysis of weight change since age 18, height, body mass index (BMI) at age 18, and current BMI and the risk of developing ovarian cancer among BRCA1 and BRCA2 mutation carriers. Methods: In this prospective cohort study, height, weight, and weight at age 18 were collected at study enrollment. Weight was updated biennially. Cox proportional hazards models were used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) for ovarian cancer. Results: This study followed 4,340 women prospectively. There were 121 incident cases of ovarian cancer. Weight gain of more than 20 kg since age 18 was associated with a 2-fold increased risk of ovarian cancer, compared with women who maintained a stable weight (HR, 2.00; 95% CI, 1.13–3.54; P = 0.02). Current BMI of 26.5 kg/m2 or greater was associated with an increased risk of ovarian cancer in BRCA1 mutation carriers, compared with those with a BMI less than 20.8 kg/m2 (Q4 vs. Q1 HR, 2.13; 95% CI, 1.04–4.36; P = 0.04). There were no significant associations between height or BMI at age 18 and risk of ovarian cancer. Conclusions: Adult weight gain is a risk factor for ovarian cancer in women with a BRCA1 or BRCA2 mutation. Impact: These findings emphasize the importance of maintaining a healthy body weight throughout adulthood in women at high risk for ovarian cancer.

Cancer incidence estimation from mortality data: a validation study within a population-based cancer registry

BackgroundPopulation-based cancer registries are required to calculate cancer incidence in a geographical area, and several methods have been developed to obtain estimations of cancer incidence in areas not covered by a cancer registry. However, an extended analysis of those methods in order to confirm their validity is still needed.MethodsWe assessed the validity of one of the most frequently used methods to estimate cancer incidence, on the basis of cancer mortality data and the incidence-to-mortality ratio (IMR), the IMR method. Using the previous 15-year cancer mortality time series, we derived the expected yearly number of cancer cases in the period 2004–2013 for six cancer sites for each sex. Generalized linear mixed models, including a polynomial function for the year of death and smoothing splines for age, were adjusted. Models were fitted under a Bayesian framework based on Markov chain Monte Carlo methods. The IMR method was applied to five scenarios reflecting different assumptions regarding the behavior of the IMR. We compared incident cases estimated with the IMR method to observed cases diagnosed in 2004–2013 in Granada. A goodness-of-fit (GOF) indicator was formulated to determine the best estimation scenario.ResultsA total of 39,848 cancer incidence cases and 43,884 deaths due to cancer were included. The relative differences between the observed and predicted numbers of cancer cases were less than 10% for most cancer sites. The constant assumption for the IMR trend provided the best GOF for colon, rectal, lung, bladder, and stomach cancers in men and colon, rectum, breast, and corpus uteri in women. The linear assumption was better for lung and ovarian cancers in women and prostate cancer in men. In the best scenario, the mean absolute percentage error was 6% in men and 4% in women for overall cancer. Female breast cancer and prostate cancer obtained the worst GOF results in all scenarios.ConclusionA comparison with a historical time series of real data in a population-based cancer registry indicated that the IMR method is a valid tool for the estimation of cancer incidence. The goodness-of-fit indicator proposed can help select the best assumption for the IMR based on a statistical argument.

First- and second-degree family history of ovarian and breast cancer in relation to risk of invasive ovarian cancer in African American and white women.

Family history (FH) of ovarian cancer and breast cancer are well-established risk factors for ovarian cancer, but few studies have examined this association in African American (AA) and white women by histotype. We assessed first- and second-degree FH of ovarian and breast cancer and risk of epithelial ovarian cancer in the Ovarian Cancer in Women of African Ancestry Consortium. Analyses included 1052 AA cases, 2328 AA controls, 2380 white cases and 3982 white controls. Race-specific odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multilevel logistic regression with adjustment for covariates. Analyses were stratified by histotype (high-grade serous vs others). First-degree FH of ovarian cancer was associated with high-grade serous carcinoma in AA (OR = 2.32, 95% CI: 1.50, 3.59) and white women (OR = 2.48, 95% CI: 1.82, 3.38). First-degree FH of breast cancer increased risk irrespective of histotype in AAs, but with high-grade serous carcinoma only in white women. Associations with second-degree FH of ovarian cancer were observed for overall ovarian cancer in white women and with high-grade serous carcinoma in both groups. First-degree FH of ovarian cancer and of breast cancer, and second-degree FH of ovarian cancer is strongly associated with high-grade serous ovarian carcinoma in AA and white women. The association of FH of breast cancer with high-grade serous ovarian carcinoma is similar in white women and AA women, but may differ for other histotypes.

Platelet RNA Signature Enables Early and Accurate Detection of Ovarian Cancer: An Intercontinental, Biomarker Identification Study

Background: Timely, accurate, and non-invasive detection of ovarian cancer in women with adnexal masses presents a significant clinical challenge. Morpho-physiological alternations accompanied by increased platelet counts was found by the long-term clinical practice and provided a rationale for investigating the potential of platelet RNA profiles to detect ovarian cancer. Methods: In this study, 928 eligible participants (ovarian cancer, n=465; benign adnexal masses, n=296; healthy women, n=167) from three Chinese and six European medical facilities were included between September 2016 and May 2019. A 102-platelet-RNA classifier, named tumour-educated platelet-derived gene panel of ovarian cancer (TEPOC), was developed by the least absolute shrinkage and selection operator (LASSO) and minimum redundancy maximum relevance (mRMR) feature selection, followed a support vector machine (SVM) model in the training cohort (TC) and validated in two domestic (VC1 and VC2) and one European (VC3) external validation cohorts. The performance of TEPOC was compared with that of carbohydrate antigen 125 (CA125), using histological diagnosis as the reference standard. Findings: TEPOC detected OC in VC1, VC2, and VC3 with the area under the receiver operating characteristic curve (AUC) values of 0·923 (0·855–0·990), 0·918 (0·872–0·963), and 0·887 (0·813–0·960), respectively, which were superior to those of CA125 (VC1: 0·735; VC2: 0·836; VC3: 0·824), P < 0.05. Compared to CA125, TEPOC exhibited higher accuracy and specificity and non-inferior sensitivity in detecting early-stage OC, non-epithelial ovarian malignancies, and borderline ovarian tumours, and discriminating OC from endometriosis. Combining the use of CA125 with TEPOC further enhanced its diagnostic performance (AUC, VC1: 0·955; VC2: 0·939; VC3: 0·917). Interpretation: TEPOC enabled early and accurate non-invasive detection of ovarian cancer and harboured robustness, compatibility, and universality that withstood validation across different races, pathological subtypes of ovarian cancer, and other malignancies. Clinical Trials: Chinese clinical trial registry (ChiCTR2100046452). Funding: National Major Science and Technology Project and Natural Science Foundation of China. Declaration of Interest: None to declare. Ethical Approval: This study was approved by the Ethical Committee of Tongji Medical College, HUST (S253) and the Ethical Committee of the LUMC (#P16.229).

Epithelial Ovarian Cancer in Women

Epithelial Ovarian Cancer in Women

Predictive Value of Complete Blood Count Inflammatory Parameters for Epithelial Ovarian Cancers in Women During Reproductive Period

Predictive Value of Complete Blood Count Inflammatory Parameters for Epithelial Ovarian Cancers in Women During Reproductive Period

Abstract PO-180: Genital powder use and risk of epithelial ovarian cancer in the Ovarian Cancer in Women of African Ancestry Consortium

Abstract PURPOSE: To date, the epidemiology of epithelial ovarian cancer (EOC) among African-American women has been severely understudied. It remains unclear to what extent variation in the prevalence of EOC risk factors may explain incidence disparities between African-American and white women. Genital powder use is more common among African-American women; however, studies of genital power use and EOC risk have been conducted predominantly in white populations, and histotype specific analyses among African-American populations are limited. The objective of this study was to evaluate the association between genital powder use and EOC risk among African-American and white women, overall and by histotype. METHODS: We used data from four ovarian cancer case-control studies in the Ovarian Cancer in Women of African Ancestry (OCWAA) consortium: the African American Cancer Epidemiology Study, the Los Angeles County Ovarian Cancer Study, the Cook County Case-Control Study, and the North Carolina Ovarian Cancer Study. Participants included 601 African-American cases, 1,012 African-American controls, 2,225 white cases, and 3,086 white controls who answered questions on genital powder use prior to 2014. The association between genital powder use and EOC risk was estimated using logistic regression. Pooled histotype specific odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using polytomous logistic regression. The population attributable risk (PAR) by race was calculated using the Bruzzi method. RESULTS: The prevalence of reporting ever genital powder use was 66% among African-American women and 44% among white women. African- American women who ever used genital powder were 29% more likely to develop EOC compared to African-American women who reported no use (OR=1.29, 95% CI=0.98-1.71). White women who ever used genital powder were 36% more likely to develop EOC compared to white women reporting no use (OR=1.36, 95% CI=1.12- 1.52). The associations were similar when examined by histotype. Among African- American women, the ORs were 1.29 (95% CI=0.94-1.76) for high grade serous (HGS) and 1.38 (95% CI=0.87-2.19) for non-HGS. For white women, the corresponding ORs were 1.27 (95% CI=1.06-1.52) and 1.21 (95% CI=0.96-1.56), respectively. The PAR for genital powder use was slightly higher, but not statistically significantly different, in African-American women (PAR=10.7, 95% CI=3.7-17.5) compared to white women (PAR=7.8, 95% CI=4.9-10.7). CONCLUSION: While the prevalence of ever genital body powder use was higher among African-American women, the associations between genital powder use and ovarian cancer risk were similar between African-American and white women, and did not materially vary by histotype. Further analyses incorporating additional OCWAA studies and using more refined exposure categories (e.g., frequency and duration of powder use, age at first application) are currently being conducted. Citation Format: Colette P. Davis, Elisa V. Bandera, Traci N. Bethea, Tareq F. Camacho, Charlotte E. Joslin, Anna H. Wu, Alicia Beeghly-Fadiel, Emily K. Cloyd, Patricia G. Moorman, Evan Myers, Heather M. Ochs-Balcom, Lauren C. Peres, Will L. Rosenow, Veronica W. Setiawan, Lynn Rosenberg, Joellen M Schildkraut, Holly R. Harris. Genital powder use and risk of epithelial ovarian cancer in the Ovarian Cancer in Women of African Ancestry Consortium [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-180.

Racial Differences in Population Attributable Risk for Epithelial Ovarian Cancer in the OCWAA Consortium.

The causes of racial disparities in epithelial ovarian cancer (EOC) incidence remain unclear. Differences in the prevalence of ovarian cancer risk factors may explain disparities in EOC incidence among African American (AA) and White women. We used data from 4 case-control studies and 3 case-control studies nested within prospective cohorts in the Ovarian Cancer in Women of African Ancestry Consortium to estimate race-specific associations of 10 known or suspected EOC risk factors using logistic regression. Using the Bruzzi method, race-specific population attributable risks (PAR) were estimated for each risk factor individually and collectively, including groupings of exposures (reproductive factors and modifiable factors). All statistical tests were 2-sided. Among 3244 White EOC cases and 9638 controls and 1052 AA EOC cases and 2410 controls, AA women had a statistically significantly higher PAR (false discovery rate [FDR] P < .001) for first-degree family history of breast cancer (PAR = 10.1%, 95% confidence interval [CI] = 6.5% to 13.7%) compared with White women (PAR = 2.6%, 95% CI = 0.8% to 4.4%). After multiple test correction, AA women had a higher PAR than White women when evaluating all risk factors collectively (PAR = 61.6%, 95% CI = 48.6% to 71.3% vs PAR = 43.0%, 95% CI = 32.8% to 51.4%, respectively; FDR P = .06) and for modifiable exposures, including body mass index, oral contraceptives, aspirin, and body powder (PAR = 36.0%, 95% CI = 21.0% to 48.8% vs PAR = 13.8%, 95% CI = 4.5% to 21.8%, respectively; FDR P = .04). Collectively, the selected risk factors accounted for slightly more of the risk among AA than White women, and interventions to reduce EOC incidence that are focused on multiple modifiable risk factors may be slightly more beneficial to AA women than White women at risk for EOC.

Mobility-related basic and instrumental activities of daily living fluctuate over 2–3 cycles of chemotherapy for ovarian cancer in women over 70: An exploratory analysis

Mobility-related basic and instrumental activities of daily living fluctuate over 2–3 cycles of chemotherapy for ovarian cancer in women over 70: An exploratory analysis

Salpingectomy for the Risk Reduction of Ovarian Cancer: Is It Time for a Salpingectomy-alone Approach?

To summarize published evidence supporting current strategies for the prevention of epithelial ovarian cancer in women with a genetic, elevated risk for the development of this disease, as well as the emerging data on the novel salpingectomy with delayed oophorectomy (SDO) strategy. Furthermore, we will explore whether salpingectomy alone is a viable risk-reducing strategy for these women. We will also discuss current national guidelines for risk-reducing surgery based on patients' individual genetic predisposition. MEDLINE, PubMed, EMBASE, and the Cochrane Database, with a focus on randomized controlled trials and large prospective, observational studies. The key search terms for our review included Medical Subject Headings: "salpingectomy," "ovarian cancer," and "risk-reducing surgery." The fallopian tube is now well established as the site of origin for most ovarian cancers, particularly high-grade serous carcinomas. This finding has led to the development of new preventive surgical techniques, such as SDO, which may be associated with fewer side effects. However, until the results of ongoing trials are reported and the impact of SDO on ovarian cancer risk reduction is established, it should not be recommended outside of clinical trials, and bilateral salpingo-oophorectomy remains the treatment of choice for risk-reducing surgery, especially in women with a genetic, high risk for ovarian cancer. The decision to undergo risk-reducing surgery among women with an elevated risk for ovarian cancer should be made after comprehensive consultation and individually based on genetic predisposition, childbearing status, and personal preference.

Development of a longitudinal two-biomarker algorithm for early detection of ovarian cancer in women with BRCA mutations

ObjectiveTo develop a longitudinal algorithm combining two biomarkers, CA125 and HE4, for early detection of ovarian cancer in women with BRCA mutations. MethodsWomen with BRCA mutations and intact ovaries were invited to participate in a novel ovarian cancer early detection prospective study. The Risk of Ovarian Cancer Algorithm (ROCA) identifying significant increases above each woman's baseline in serum CA125 and HE4 was performed every four months; abnormal risks triggered a subsequent ultrasound. The study first used a risk algorithm for only CA125, a second algorithm was developed for HE4 and finally a risk algorithm combining the two biomarkers was implemented. The ROCA strategy was compared to Standard of Care (SOC) surveillance strategy. ResultsA total of 149 women enrolled in the ROCA arm while 43 women enrolled in the SOC arm. Abnormal scores were found in 24% of ROCA CA125 tests, 16% if ROCA CA125 or the novel ROCA HE4 were used independently and reduced to 8% using the new two-marker ROCA, significantly lower than the 15% of abnormal tests seen in the SOC arm (p = 0.042). The average false positive rate among women without ovarian cancer for two-marker ROCA for referral to ultrasound was 6.6% (specificity 93.4%), and for the two-marker ROCA plus ultrasound for referral to surgical consultation was 1.7% (specificity 98.3%). ConclusionA newly developed two-marker ROCA administered every 4 months had lower call-back rates than SOC surveillance. Having established high specificity, the two-marker ROCA score deserves further evaluation for sensitivity in a larger trial.

Ovarian cancer in women with known BRCA mutations: How much screening is too much?

Ovarian cancer in women with known BRCA mutations: How much screening is too much?

Mobility-related basic and instrumental activities of daily living fluctuate over 2-3 cycles of chemotherapy for ovarian cancer in women over 70: An exploratory analysis

Objective: The purpose of this exploratory secondary analysis was to describe trajectories of activities of daily living (ADLs) and instrumental ADL (iADLs) ability in older (age >70 years) ovarian cancer (OC) patients over the course of chemotherapy, to inform selection of activities to query in prospectively monitoring for supportive care needs to improve chemotherapy tolerance.

Abstract 1180: Estimating the contribution of epidemiologic risk factors to racial differences in epithelial ovarian cancer incidence

Abstract Purpose. Although the incidence of epithelial ovarian cancer is highest among non-Hispanic white women, African-American women have the worst survival of all racial/ethnic groups. We hypothesize that differences in the prevalence of known and suspected ovarian cancer risk factors may explain a portion of the differences in incidence of epithelial ovarian cancer between white and African-American women. Methods. We used data from seven U.S. studies in the Ovarian Cancer in Women of African Ancestry (OCWAA) consortium, the North Carolina Ovarian Cancer Study (NCOCS), the Los Angeles Ovarian Cancer Study (LACOCS), the African-American Cancer Epidemiology Study (AACES), the Cook County Case-Control Study (CCCCS), the Black Women's Health Study (BWHS), the Women's Health Initiative (WHI), and the Multiethnic Cohort Study (MEC). The association between each known or suspected ovarian cancer risk factor (age, parity, oral contraceptive use, tubal ligation, body mass index (BMI), family history of ovarian and breast cancer, menopausal status, education, hysterectomy, aspirin use, talcum powder applied to genital areas, endometriosis, and age at menarche) was estimated using logistic regression with study site interactions to capture heterogeneity across studies. Using the Bruzzi method, population attributable risks (PAR) were calculated by race for each risk factor individually and collectively for all risk factors. Results. The comparison of 3,249 white ovarian cancer cases and 9,650 controls to 1,054 African-American cases and 2,410 controls revealed notable differences in the PAR of several risk factors by race. African-American women had a statistically significantly higher PAR for family history of breast cancer and BMI ≥30kg/m2compared to white women (10.0% vs. 2.5% and 8.9% vs. 0.4%, respectively). Although not statistically significant, white women had a higher PAR for oral contraceptive use (duration &amp;lt;5 years) and not having had a tubal ligation than African-American women. When evaluating all risk factors collectively, the overall PAR was 63.9% for African-American women and 48.0% for white women. We also calculated overall PARs excluding WHI due to differences in the inclusion criteria for WHI compared to the other population-based studies in OCWAA: 65.7% for African-American women and 57.8% for white women. Conclusions. Our findings suggest that the known and suspected ovarian cancer risk factors investigated in this study may be partially responsible for differences in ovarian cancer incidence between white and African-American women. Although important across both racial groups, collectively, the factors studied accounted for slightly more of the ovarian cancer risk among African-American women than white women. Citation Format: Lauren C. Peres, Tareq F. Camacho, Elisa V. Bandera, Traci N. Bethea, Charlotte E. Joslin, Anna H. Wu, Alicia Beeghly-Fadiel, Emily K. Cloyd, Holly R. Harris, Patricia G. Moorman, Evan Myers, Heather M. Ochs-Balcom, Will L. Rosenow, Veronica W. Setiawan, Lynn Rosenberg, Joellen M. Schildkraut. Estimating the contribution of epidemiologic risk factors to racial differences in epithelial ovarian cancer incidence [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1180.

Abstract 2317: Genetic risk scores from structural variation predict life-time individual cancer risk

Abstract Background. The current best predictor of lifetime risk for many forms of cancer is family history. Family history is transmitted through germ line DNA. Analysis of germ-line DNA should be able to predict lifetime risk at least as well family history. Genetic risk scores, used to predict lifetime risk from DNA, usually consist of linear combinations of SNPs. These scores ignore structural variations and epistatic effects (non-linear combinations). The objective of this study is to test whether germline DNA structural information along with machine learning algorithms, which can use non-linear combinations, can be used to predict whether a person will develop different types of cancer. Methods. We tested this objective using data compiled by The Cancer Genome Atlas (TCGA) project and the UK Biobank. The TCGA data consisted of information on DNA chromosome scale length variation extracted from the peripheral blood of 8,821 different patients, each of whom had one of 32 different types of cancer. The UK Biobank data consisted of about 1500 women diagnosed with breast cancer (cases) and about 5000 women who have no record of any type of cancer(controls). We characterized structural variation by a quantitative measure of chromosomal-scale length variation. Chromosomal-scale length variation is computed from array data. A person's DNA (chromosomes 1-22) can be characterized by a series of 22 numbers, each representing the log base 2 ratio of the chromosome's length compared to the average chromosome length. Using these 22 numbers for each person, we set up a machine learning classification problem to differentiate those people diagnosed with a particular form of cancer from those who have not been diagnosed with that cancer. We used the h2o libraries in R to test how well different machine-learning algorithm can classify with these datasets. Results. In two independent datasets, the Cancer Genome Atlas (TCGA) project and the UK Biobank, we could classify whether or not a patient had a certain cancer based solely on chromosomal scale length variation. We found that all 32 different types of cancer in the TCGA dataset tested could be predicted better than chance using structural variation data. Specifically, in the TCGA dataset we measured the area under the receiver operator curve, known as the AUC, for ovarian cancer in women (0.89), glioblastoma multiforme (0.86), breast cancer in women (0.75), and colon adenocarcinoma (0.79), with a 95% confidence interval width of less than 0.01 in each case. This method could predict 10% of glioblastoma multiforme cases with less than 1 in 10,000 false positives in the TCGA dataset. In the UK Biobank dataset, we could predict breast cancer in women with an AUC=0.83. Conclusion. Genetic risk scores based on structural variation can effectively predict whether a person will eventually develop may different types of cancer. Citation Format: Chris Toh, Charmeine Ko, James P. Brody. Genetic risk scores from structural variation predict life-time individual cancer risk [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2317.

Abstract 4289: Detection of germline large genomic rearrangements in BRCA1/2 genes by a capture-based NGS panel reveals its contribution to Chinese patients with solid tumors

Abstract Background: Germline mutations in BRCA1/2 genes have been found associate with risk to develop breast and ovarian cancer in women. Patients with these mutations are also highly sensitive to PARP inhibitors. However, current NGS-based method lacks the capability to accurately detect large genomic rearrangements (LGR) including exon level deletions and duplications. Method: We have enhanced our capture-based NGS panel and developed an algorithm to detect LGRs in BRCA1/2 genes. We applied the method to retrospectively profile germline DNA from over 14,000 patients with solid tumors, including 367 ovarian cancers and 574 breast cancers. Samples with positive test results for exon level deletions or duplications were subsequently confirmed by MLPA. Results: Out of the 14,000 patients, we identified 19 patients with exon level deletions (BRCA1, n = 16; BRCA2, n = 3) and 7 with duplications (BRCA1, n = 6; BRCA2, n = 1). The germline LGR events were predominantly found in ovarian and breast cancer patients with a frequency of 1.9% (7/367) in ovarian cancer and a frequency of 1.2% (7/574) in breast cancer. We also observed occasional findings in non-small cell lung cancer, colorectal cancer as well as gastric cancer. From these LGRs, BRCA1 exon 2del (n = 4), BRCA1 exon 7del (n = 4) and BRCA1 exon 17-18del (n = 3) are the most recurrent LGRs observed. Conclusion: We here report a method to comprehensively evaluate the germline LGRs in BRCA1 and BRCA2 genes using the capture-based NGS panel. We verified the results by MLPA as an orthogonal assay and report the population frequency of LGRs occurrence in Chinese patients with solid tumors. Citation Format: Jing Li, Bo Yang, Kefei Huang, Changhao Liu, Hua Dong, Jie Wang, Fugen Li, Zhong-qiu Lin. Detection of germline large genomic rearrangements in BRCA1/2 genes by a capture-based NGS panel reveals its contribution to Chinese patients with solid tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4289.

Incidence and Risk Factors of Ovarian Cancer and Breast Cancer Following Prophylactic Surgery: A Retrospective Cohort Study

Objective: The purpose of this study was to review the clinical variables associated with developing a breast or ovarian cancer in women diagnosed with a positive BRCA1/2 germline mutation or a fam...