HOXB13

Achieved FY2023 financial guidance FY2023 full year revenue grew 10% over prior year Webcast today, May 25, 2023 at 4:30 p.m. Eastern Time SOUTH SAN FRANCISCO, Calif., May 25, 2023 (GLOBE NEWSWIRE) -- 23andMe Holding Co. (Nasdaq: ME) (23andMe), a leading human genetics and biopharmaceutical company with a mission to help people access, understand, and benefit from the human genome, today reported its financial results for the fourth quarter (Q4) and full year of fiscal year 2023 (FY2023), which ended March 31, 2023. 23andMe is the only company with multiple U.S. Food and Drug Administration (FDA) authorizations for over-the-counter genetic health risk reports. The Company has also created the world’s largest, re-contactable crowdsourced platform of genotypic information paired with billions of phenotypic data points contributed by engaged customers. This unique platform enables the Company to discover new genetic insights, develop impactful risk prediction reports for common health conditions, and accelerate the identification of novel drug discovery programs rooted in human genetics across a spectrum of disease areas. “23andMe had a productive year with numerous consumer and therapeutics business milestones. We grew our customer base to over 14 million genotyped customers, and launched 11 new health reports for our 23andMe+ members, including the first and only direct-to-consumer FDA-authorized report on hereditary prostate cancer. As we continue to add value to our subscription product and integrate Lemonaid’s telehealth and pharmacy services, we believe we can truly help fulfill the promise of personalized care,” said Anne Wojcicki, Chief Executive Officer and Co-Founder of 23andMe. “Our Therapeutics group continues to advance a number of programs, including 23ME-00610, a wholly-owned immunotherapy currently in the Phase 2a portion of a Phase 1/2a study. We also remain well positioned to pursue collaborations with multiple pharma partners on a number of drug discovery and development and disease awareness efforts. By enhancing our efforts to provide a leading genetics-based health service and utilizing our discovery engine for new therapeutics, we have the opportunity to transform how we predict, prevent and treat diseases in the future.” Full Year FY2023 Financial Results Summary Delivered full year performance in FY23 that was within or better than guidance. $299 million revenue$312 million net loss$161 million Adjusted EBITDA deficit Solid balance sheet with cash of $387 million at year end. Recent Highlights ConsumerThe Company continued to add reports for 23andMe+ members, and launched a collaboration with Novartis for disease awareness. Launched three new reports for 23andMe+ members in the fourth quarter, and 11 total member-exclusive report launches in FY2023.The new reports released in the fourth quarter include: Preeclampsia PRS reportAttention deficit/hyperactivity disorder PRS reportHereditary prostate cancer (HOXB13-related) genetic health risk report Announced a collaboration with Novartis Pharmaceuticals Corporation to increase awareness for Lipoprotein(a) (Lp(a)). High levels of Lp(a) are associated with increased risk of heart attack, stroke and other life threatening conditions. The level of Lp(a) is almost entirely determined by genes and is unrelated to diet, exercise or obesity, creating the need for greater awareness. Therapeutics The Company continued to progress its wholly-owned 23ME-00610 program in the clinic. Presented results from the Phase 1 portion of the first-in-human Phase 1/2a study of 23ME-00610 in a poster at the 2023 American Association for Cancer Research (AACR) Annual Meeting. The results showed 23ME-00610 demonstrated an acceptable safety and tolerability profile, with favorable pharmacokinetics and peripheral CD200R1 saturation in patients with advanced solid malignancies.Dosed the first patient in the Phase 2a portion of its Phase 1/2a study evaluating the anti-tumor activity of the 23ME-00610 monotherapy in a number of previously disclosed expansion cohorts. Dosing will be at 1400 mg intravenously every 3 weeks based on Phase 1 data. The Phase 2a portion of the study will further characterize the safety, tolerability, pharmacokinetic and pharmacodynamic profile of 23ME-00610. CorporateThe Company added to its experienced leadership team and published its first ESG report. Announced the appointment of Reza Afkhami as Chief Corporate Development Officer overseeing corporate development efforts across the Company’s therapeutics, research services and consumer groups. Afkhami will lead the Company’s current efforts to pursue a wide range of collaborations, including leveraging the Company’s pipeline of genetically validated discovery and clinical programs, as well as patient recruitment and disease awareness campaigns.Published inaugural environmental social and governance (ESG) report that outlines the Company’s strategy and initiatives to ensure ethical management, promote a diverse and equitable culture, and implement sustainable business operations. The full report is available to view here. “Our 2023 fiscal year was important for 23andMe as we continued to prioritize the roll out of our next-generation genomic health services and advance our therapeutics efforts, while also remaining focused on growing our consumer business,” said Joe Selsavage, Interim Chief Financial and Accounting Officer of 23andMe. “We continue to use a disciplined approach in the advancement of our therapeutics portfolio and to focus our efforts on creating a new customer experience with our prevention-based genetic health services, further enabling our opportunities for growth.” FY2023 Fourth Quarter and Full Year Financial ResultsTotal revenue for the three and twelve months ended March 31, 2023, was $92 million and $299 million, respectively, compared to $101 million and $272 million, respectively, for the same periods in the prior year, representing a decrease of 8% and an increase of 10%, respectively. The decrease in fourth quarter revenue was primarily driven by a decrease in Research Services revenue from the GSK collaboration as the prior year included a cumulative revenue adjustment due to a change in estimate of total project resources, resulting in a higher percentage of completion to date, and a decrease in Consumer Services revenue from lower volumes on Personal Genome Service (PGS) kit sales as we focused on driving improved margins through higher average selling prices. Full year revenue growth was primarily driven by an increase in Consumer Services revenue attributable to a full year of telehealth services revenue from the Lemonaid Health Acquisition, whereas the prior year included only 5 months, and an increase in subscription services revenue, partially offset by a decrease in PGS kit revenue. Research Services revenue increased primarily due to an increase in GSK collaboration revenue related to GSK exercising their option to extend the exclusive target discovery period of our collaboration for a fifth year and an increase in revenue under research contracts with third parties. Revenue from Consumer Services, which includes PGS, telehealth and subscription services, represented approximately 88% and 83% of total revenue, respectively, for the three and twelve months ended March 31, 2023. Research Services revenue is primarily derived from the collaboration with GSK and accounted for approximately 12% and 17% of total revenue, respectively, for those same periods. Operating expenses for the three and twelve months ended March 31, 2023, were $109 million and $459 million, respectively, compared to $117 million and $387 million, respectively, for the same periods in the prior year. The decrease in operating expenses in the three-month period was primarily due to a one time net litigation settlement payment in fiscal year 2022 and timing differences in marketing campaigns and fewer promotional windows between the comparative periods. The increase in operating expenses in the twelve-month period was primarily attributable to increased personnel-related expenses driven by increased salaries and related taxes as a result of inflation and headcount growth, and a non-cash impairment charge of an intangible asset. These increases in operating expenses were primarily related to the previously acquired telehealth business. Net loss for the three and twelve months ended March 31, 2023, was $64 million and $312 million, respectively, compared to a net loss of $70 million and $217 million, respectively, for the same periods in the prior year. The improvement in the three-month period was primarily attributable to lower operating expenses (as noted above) and an increase in interest income from interest yields earned on cash held in money market funds. The increase in the twelve-month period was primarily attributable to the increase in operating expenses discussed above, as well as a benefit from change in fair value of warrant liabilities of $33 million and an income tax benefit of $3 million in the twelve months ended March 31, 2022. Total Adjusted EBITDA (as defined below) for the three and twelve months ended March 31, 2023, was a deficit of $39 million and $161 million, respectively, compared to a deficit of $30 million and $151 million, respectively, for the same periods in the prior year. The increase in the Adjusted EBITDA deficit for the three and twelve-month periods was primarily due to the increase in operating expenses noted above. Please refer to the tables below for a reconciliation of U.S. GAAP to Non-U.S. GAAP financial measures. Balance Sheet23andMe ended March 31, 2023 with cash and cash equivalents of $387 million, compared to $553 million as of March 31, 2022. FY2024 Financial GuidanceThe Company’s full year fiscal 2024 guidance is based on a conservative approach, recognizing the current uncertainties in the general economy and financial markets. Within the existing Consumer businesses of PGS and telehealth, the Company is prioritizing the minimization of cash burn over initiatives intended to create incremental top-line growth. For those areas of the business expected to drive future growth, which include the Company’s new genomic health services and Therapeutics, the Company plans to focus on the most strategically and financially valuable allocation of capital and invest appropriately. Given the Company’s shift in focus to higher margins rather than volume growth in PGS and telehealth, as well as the end of the target discovery term of the GSK collaboration, the Company does not foresee meaningful revenue contribution from these areas of Consumer in FY2024. Revenue guidance for FY2024, which will end on March 31, 2024, is projected to be in the range of $255 million to $280 million, with a net loss in the range of $340 million to $365 million. Full year adjusted EBITDA deficit is projected to be in the range of $170 to $195 million for fiscal year 2024. The Adjusted EBITDA guidance, assumes the following: We will continue to advance our current Therapeutic assetsNo additional revenue from new strategic partnershipsNo savings incurred from cost reduction initiatives, such as those related to the evaluation of opting-in or out of our GSK programs, out-licensing or partnering on our therapeutic programs or other internal operating cost reductions Adjusted EBITDA is our best proxy for cash burn and we do not assume the sale of any equity under our At-the-Market Sales program with Cowen and Company, LLC (the “ATM Program”). Conference Call Webcast Information23andMe will host a conference call at 4:30 p.m. Eastern Time on Thursday, May 25, 2023 to discuss the financial results for the full year and Q4 FY2023 and report on business progress. The webcast can be accessed on the day of the event at https://investors.23andme.com/news-events/events-presentations. A webcast replay will be available at the same address for a limited time within 24 hours after the event. About 23andMe23andMe is a genetics-led consumer healthcare and therapeutics company empowering a healthier future. For more information, please visit investors.23andme.com. Additional InformationThis press release shall not constitute an offer to sell or a solicitation of an offer to buy any of the securities, nor shall there be any sale of these securities, in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction. Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, including, without limitation, statements regarding the future performance of 23andMe’s Consumer and Research Services and Therapeutics businesses, the growth and potential of its proprietary research platform ,the development of the Company’s products and therapeutics programs, and access to and use of the ATM Program, including potential sales of shares pursuant thereto and the benefits thereof. All statements, other than statements of historical fact, included or incorporated in this press release, including statements regarding 23andMe’s expected future operating results, strategy, financial position, funding for continued operations, cash reserves, projected costs, plans, and objectives of management, are forward-looking statements. The words "believes," "anticipates," "estimates," "plans," "expects," "intends," "may," "could," "should," "potential," "likely," "projects," “predicts,” "continue," "will," “schedule,” and "would" or, in each case, their negative or other variations or comparable terminology, are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These forward-looking statements are predictions based on 23andMe’s current expectations and projections about future events and various assumptions. 23andMe cannot guarantee that it will actually achieve the plans, intentions, or expectations disclosed in its forward-looking statements and you should not place undue reliance on 23andMe’s forward-looking statements. These forward-looking statements involve a number of risks, uncertainties (many of which are beyond the control of 23andMe), or other assumptions that may cause actual results or performance to differ materially from those expressed or implied by these forward-looking statements. The forward-looking statements contained herein are also subject generally to other risks and uncertainties that are described from time to time in the Company’s filings with the Securities and Exchange Commission, including under Item 1A, “Risk Factors” in the Company’s most recent Annual Report on Form 10-K, as filed with the Securities and Exchange Commission, and as revised and updated by our Quarterly Reports on Form 10-Q and Current Reports on Form 8-K. The statements made herein are made as of the date of this press release and, except as may be required by law, 23andMe undertakes no obligation to update them, whether as a result of new information, developments, or otherwise. Use of Non-GAAP Financial MeasureTo supplement the 23andMe’s unaudited condensed consolidated statements of operations and unaudited condensed consolidated balance sheets, which are prepared in conformity with generally accepted accounting principles in the United States of America (GAAP), this press release also includes references to Adjusted EBITDA, which is a non-GAAP financial measure that 23andMe defines as net income (loss) before net interest income (expense), net other income (expense), income tax expenses (benefit), depreciation and amortization, impairment charges, stock-based compensation expense, acquisition-related costs, and other items that are considered unusual or not representative of underlying trends of our business, including but not limited to: changes in fair value of warrant liabilities, litigation settlement, and restructuring and other charges, if applicable for the periods presented. 23andMe has provided a reconciliation of net loss, the most directly comparable GAAP financial measure, to Adjusted EBITDA at the end of this press release. Adjusted EBITDA is a key measure used by 23andMe’s management and the board of directors to understand and evaluate operating performance and trends, to prepare and approve 23andMe’s annual budget and to develop short- and long-term operating plans. 23andMe provides Adjusted EBITDA because 23andMe believes it is frequently used by analysts, investors and other interested parties to evaluate companies in its industry and it facilitates comparisons on a consistent basis across reporting periods. Further, 23andMe believes it is helpful in highlighting trends in its operating results because it excludes items that are not indicative of 23andMe’s core operating performance. In particular, 23andMe believes that the exclusion of the items eliminated in calculating Adjusted EBITDA provides useful measures for period-to-period comparisons of 23andMe’s business. Accordingly, 23andMe believes that Adjusted EBITDA provides useful information in understanding and evaluating operating results in the same manner as 23andMe’s management and board of directors. In evaluating Adjusted EBITDA, you should be aware that in the future 23andMe will incur expenses similar to the adjustments in this presentation. 23andMe’s presentation of Adjusted EBITDA should not be construed as an inference that future results will be unaffected by these expenses or any unusual or non-recurring items. Adjusted EBITDA should not be considered in isolation of, or as an alternative to, measures prepared in accordance with GAAP. Other companies, including companies in the same industry, may calculate similarly-titled non-GAAP financial measures differently or may use other measures to evaluate their performance, all of which could reduce the usefulness of Adjusted EBITDA as a tool for comparison. There are a number of limitations related to the use of these non-GAAP financial measures rather than net loss, which is the most directly comparable financial measure calculated in accordance with GAAP. Some of the limitations of Adjusted EBITDA include (i) Adjusted EBITDA does not properly reflect capital commitments to be paid in the future, and (ii) although depreciation and amortization are non-cash charges, the underlying assets may need to be replaced and Adjusted EBITDA does not reflect these capital expenditures. When evaluating 23andMe’s performance, you should consider Adjusted EBITDA alongside other financial performance measures, including net loss and other GAAP results. ContactsInvestor Relations Contact: investors@23andMe.comMedia Contact: press@23andMe.com 23andMe Holding Co.Condensed Consolidated Statements of Operations and Comprehensive Loss(In thousands, except share and per share data)(Unaudited) Three Months EndedMarch 31, Year EndedMarch 31, 2023 2022 2023 2022 Revenue $92,377 $100,559 $299,489 $271,893 Cost of revenue 52,395 53,502 164,993 138,948 Gross profit 39,982 47,057 134,496 132,945 Operating expenses: Research and development 60,719 50,324 222,596 189,377 Sales and marketing 21,779 29,351 119,927 100,338 General and administrative 26,758 36,836 115,984 97,383 Total operating expenses 109,256 116,511 458,507 387,098 Loss from operations (69,274) (69,454) (324,011) (254,153)Other income (expense): Interest income, net 4,369 64 9,676 277 Change in fair value of warrant liabilities — — — 32,989 Other income (expense), net 174 (122) (93) (83)Loss before income taxes (64,731) (69,512) (314,428) (220,970)Benefit from income taxes (633) 32 (2,772) (3,480)Net loss (64,098) (69,544) (311,656) (217,490)Other comprehensive income (loss), net of tax (309) 215 (799) 179 Total comprehensive loss $(64,407) $(69,329) $(312,455) $(217,311)Net loss per share of Class A and Class B common stock attributable to common stockholders: Basic and diluted $(0.14) $(0.16) $(0.69) $(0.60)Weighted-average shares used to compute net loss per share: Basic and diluted 456,254,405 444,139,193 451,504,377 361,528,119 23andMe Holding Co.Condensed Consolidated Balance Sheets(In thousands, except share and per share amounts)(Unaudited) March 31, March 31, 2023 2022 ASSETS Current assets: Cash and cash equivalents $386,849 $553,182 Restricted cash 1,399 1,599 Accounts receivable, net 1,897 3,380 Inventories 10,247 10,789 Deferred cost of revenue 5,376 7,700 Prepaid expenses and other current assets 19,224 25,139 Total current assets 424,992 601,789 Property and equipment, net 38,608 49,851 Operating lease right-of-use assets 56,078 55,577 Restricted cash, noncurrent 6,974 6,974 Internal-use software, net 15,661 9,635 Intangible assets, net 45,520 73,905 Goodwill 351,744 351,744 Other assets 3,021 2,593 Total assets $942,598 $1,152,068 LIABILITIES AND STOCKHOLDERS’ EQUITY Current liabilities: Accounts payable $12,924 $37,930 Accrued expenses and other current liabilities 66,430 44,588 Deferred revenue 62,521 62,939 Operating lease liabilities 7,541 7,784 Total current liabilities 149,416 153,241 Operating lease liabilities, noncurrent 77,763 78,524 Other liabilities 1,480 4,647 Total liabilities 228,659 236,412 Stockholders' equity Preferred stock - par value $0.0001, 10,000,000 shares authorized as of March 31, 2023 and 2022; zero shares issued and outstanding as of March 31, 2023 and 2022 — — Common stock, par value $0.0001 - Class A shares, 1,140,000,000 shares authorized, 293,020,474 and 228,174,718 shares issued and outstanding as of March 31, 2023 and 2022, respectively; Class B shares, 350,000,000 shares authorized, 168,179,488 and 220,637,603 shares issued and outstanding as of March 31, 2023 and 2022, respectively 46 45 Additional paid-in capital 2,220,897 2,110,160 Accumulated other comprehensive income (loss) (620) 179 Accumulated deficit (1,506,384) (1,194,728)Total stockholders’ equity 713,939 915,656 Total liabilities and stockholders’ equity $942,598 $1,152,068 23andMe Holding Co.Condensed Consolidated Statements of Cash Flows(In thousands)(Unaudited) Year Ended March 31, 2023 2022 Cash flows from operating activities: Net loss $(311,656) $(217,490)Adjustments to reconcile net loss to net cash used in operating activities: Depreciation and amortization 32,071 23,699 Amortization and impairment of internal-use software 4,427 2,449 Stock-based compensation expense 116,017 57,933 Changes in fair value of warrant liabilities — (32,989)Impairment of long-lived assets 10,126 — Other 77 85 Changes in operating assets and liabilities: Accounts receivable, net 1,483 (899)Inventories 542 (4,262)Deferred cost of revenue 2,325 (2,219)Prepaid expenses and other current assets 6,653 (10,077)Operating right-of-use assets 7,393 7,078 Other assets (429) (1,820)Accounts payable (24,573) 22,856 Accrued expenses and other current liabilities 2,671 8,316 Deferred revenue (418) (8,799)Operating lease liabilities (8,934) (7,054)Other liabilities (3,165) (3,635)Net cash used in operating activities (165,390) (166,828)Cash flows from investing activities: Purchases of property and equipment (4,043) (3,967)Purchases of intangible assets — (5,500)Capitalized internal-use software costs (7,262) (4,505)Cash paid for acquisitions, net of cash acquired — (94,165)Net cash used in investing activities (11,305) (108,137)Cash flows from financing activities: Proceeds from exercise of stock options 4,203 16,998 Proceeds from issuance of common stock under employee stock purchase plan 6,464 — Payments for taxes related to net share settlement of equity awards (197) — Payments of deferred offering costs (693) (30,642)Proceeds from issuance of common stock upon merger — 309,720 Proceeds from PIPE — 250,000 Proceeds from exercise of merger warrants — 44 Payment for warrant redemptions — (116)Net cash provided by financing activities 9,777 546,004 Effect of exchange rates on cash and cash equivalents 385 (146)Net increase (decrease) in cash, cash equivalents and restricted cash (166,533) 270,893 Cash, cash equivalents and restricted cash—beginning of period 561,755 290,862 Cash, cash equivalents and restricted cash—end of period $395,222 $561,755 Reconciliation of cash, cash equivalents, and restricted cash within the consolidated balance sheets to the amounts shown in the consolidated statements of cash flows above: Cash and cash equivalents $386,849 $553,182 Restricted cash, current 1,399 1,599 Restricted cash, noncurrent 6,974 6,974 Total cash, cash equivalents and restricted cash $395,222 $561,755 23andMe Holding Co.Total Company and Segment Information and Reconciliation of Non-GAAP Financial Measures(In thousands)(Unaudited) The Company’s revenue and Adjusted EBITDA by segment and for the total Company is as follows: Three Months EndedMarch 31, Year EndedMarch 31, 2023 2022 2023 2022 Segment Revenue:(1) Consumer and Research Services $92,377 $100,559 $299,489 $271,893 Segment Adjusted EBITDA: Consumer and Research Services Adjusted EBITDA $4,989 $3,120 $(17,997) $(30,112)Therapeutics Adjusted EBITDA (29,904) (19,898) (88,503) (76,944)Unallocated Corporate (2) (13,744) (12,992) (54,801) (43,684)Total Adjusted EBITDA $(38,659) $(29,770) $(161,301) $(150,740)Reconciliation of net loss to Adjusted EBITDA: Net loss $(64,098) $(69,544) $(311,656) $(217,490)Adjustments: Interest income, net (4,369) (64) (9,676) (277)Other (income) expense, net (174) 122 93 83 Change in fair value of warrant liabilities — — — (32,989)Income tax expense (benefit) (633) 32 (2,772) (3,480)Depreciation and amortization 4,727 4,711 20,239 18,899 Amortization of acquired intangible assets 3,639 4,371 16,486 7,269 Impairment of acquired intangible asset — — 9,968 — Stock-based compensation expense 22,249 20,460 116,017 57,933 Acquisition-related costs (3) — 192 — 9,362 Litigation settlement (4) — 9,950 — 9,950 Total Adjusted EBITDA $(38,659) $(29,770) $(161,301) $(150,740) (1) There was no Therapeutics revenue for all periods presented.(2) Certain department expenses such as Finance, Legal, Regulatory and Supplier Quality, Corporate Communications, and CEO Office are not reported as part of the reporting segments as reviewed by the CODM. These amounts are included in Unallocated Corporate.(3) For the fiscal year ended March 31, 2022, acquisition-related costs primarily consisted of advisory, legal and consulting fees related to the Lemonaid Acquisition.(4) For the fiscal year ended March 31, 2022, litigation settlement is litigation cost net of insurance recoveries, which is not expected to occur on a recurring basis and not part of the Company's normal and continued business activity. 23andMe Holding Co.Reconciliation of GAAP Net Loss Outlook to non-GAAP Adjusted EBITDA Outlook(in thousands)(Unaudited) Outlook for the Year Ending March 31, 2024 as of March 31, 2023 Low High Reconciliation of estimated net loss to adjusted EBITDA: GAAP Net Loss outlook $(365,000) $(340,000)Adjustments Estimated interest (income) expense, net (11,000) (11,000)Estimated other (income) expenses, net — — Estimated depreciation and amortization 21,000 21,000 Estimated amortization of acquired intangible assets 11,000 11,000 Estimated stock-based compensation expense 149,000 149,000 Non-GAAP adjusted EBITDA outlook $(195,000) $(170,000)

Scientists have created a comprehensive tool for predicting an individual's risk of developing prostate cancer, which they say could help ensure that those men at greatest risk will receive the appropriate testing while reducing unnecessary -- and potentially invasive -- testing for those at very low risk. Cambridge scientists have created a comprehensive tool for predicting an individual's risk of developing prostate cancer, which they say could help ensure that those men at greatest risk will receive the appropriate testing while reducing unnecessary -- and potentially invasive -- testing for those at very low risk. CanRisk-Prostate, developed by researchers at the University of Cambridge and The Institute of Cancer Research, London, will be incorporated into the group's CanRisk web tool, which has now recorded almost 1.2 million risk predictions. The free tool is already used by healthcare professionals worldwide to help predict the risk of developing breast and ovarian cancers. Prostate cancer is the most common type of cancer in men. According to Cancer Research UK, over 52,000 men are diagnosed with the disease each year and there are more than 12,000 deaths. Over three-quarters (78%) of men diagnosed with prostate cancer survive for over ten years, but this proportion has barely changed over the past decade in the UK. Testing for prostate cancer involves a blood test that looks for a protein known as a prostate-specific antigen (PSA) that is made only by the prostate gland; however, it is not always accurate. According to the NHS website, around three in four men with a raised PSA level will not have cancer. Further tests, such as tissue biopsies or MRI scans, are therefore required to confirm a diagnosis. Professor Antonis Antoniou from the Department of Public Health and Primary Care at the University of Cambridge said: "Prostate cancer is the most common cancer in men in the UK, but population-wide screening based on PSA isn't an option: these tests are often falsely positive, which means that many men would then be biopsied unnecessarily. Also, many prostate tumours identified by PSA tests are slow-growing and would not have been life-threatening. The treatment of these tumours may do more harm than good. "What we need is a way of identifying those men who are at greatest risk, allowing us to target screening and diagnostic tests where they are most needed, while also reducing the harms for those men who have low risk of the disease. This is what CanRisk-Prostate aims to do. For the first time, it combines information on the genetic makeup and prostate cancer family history, the main risk factors for the disease, to provide personalised cancer risks." Prostate cancer is one of the most genetically determined of common cancers. Inherited faulty versions of the BRCA2, HOXB13 and possibly BRCA1 genes are associated with moderate-to-high risk of prostate cancer, though such faults are rare in the population. In addition, there are several hundred more common genetic variants that each confer a lower risk, but in aggregate they act like 'volume control' that moderate or increase the prostate cancer risk. Writing in the Journal of Clinical Oncology, the researchers -- supported by Cancer Research UK -- describe the development of the first comprehensive prostate cancer model using genetic and cancer family history data from almost 17,000 families affected by prostate cancer. It uses data on rare genetic faults in moderate-to-high-risk genes and a risk score based on 268 common low-risk variants, together with detailed cancer family history, to predict the future risks. One in six men (16%) will develop prostate cancer by the time they are 85 years old. Using the model, the team found that the predicted risk was higher for men who had a father diagnosed with prostate cancer -- 27% if the father was diagnosed at an older age (80 years) but as high as 42% if the father was diagnosed at a young age (50 years). The risks were considerably higher for men with genetic faults. For example, 54% of men who carry an alteration in the BRCA2 gene would develop prostate cancer -- however, among men with BRCA2 gene faults, the risks were substantially lower if they also had a small number of the low-risk variants, but much higher if they also had a large number of the low-risk variants. In practice, say the researchers, clinicians will be able to use any combination of cancer family history, rare and common genetic variants to provide a personalised risk. To validate their model, the team ran the risk model on an independent cohort of over 170,000 men recruited to UK Biobank, a biomedical database and research resource containing anonymised genetic, lifestyle and health information from half a million UK participants. All of these men were free from prostate cancer when they were recruited to the study, but more than 7,600 developed prostate cancer within the subsequent ten years. When validating their model, the researchers found that 86% of the UK Biobank participants who developed cancer were in the half of men with the highest predicted risks, which suggests that it may be possible to target screening and diagnostic tests to the subgroup of the population at highest risk, among whom the majority of the cancers will occur. Dr Tommy Nyberg from the MRC Biostatistics Unit at Cambridge said: "We've created the most comprehensive tool to date for predicting a man's risk of developing prostate cancer. We hope this will help clinicians and genetic counsellors assess their clients' risk and provide the appropriate follow-up. "Over the next 12 months, we aim to build this tool into the widely used CanRisk tool, which will facilitate the risk-based clinical management of men seen in family cancer clinics and enable risk-adapted early detection approaches to the population at large." Professor Ros Eeles from The Institute of Cancer Research, London and co-author on the study said: "This is an important step forward as it will enable clinicians to have conversations with men about their individual risk of prostate cancer based on the most accurate computer model to date. This will help them in making decisions about screening." So far, the data used to develop CanRisk-Prostate has been from men of European ancestry. The team hope to be able to include data from men of other ethnicities as further research is undertaken. The University of Cambridge recently launched the Early Cancer Institute with the aim of detecting cancer early enough to cure it. It is the first physical institute in the UK dedicated to early cancer. A new Cambridge Cancer Research Hospital is also planned for the near future, bringing together clinical and research expertise in a new, world-class hospital, designed in partnership with patients. There is also an Early Detection and Diagnosis centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust where a prostate risk clinic has been established to translate these findings into targeted screening programmes. The research was supported by the Cancer Research UK-funded CanRisk programme. Additional support for CanRisk-Prostate was provided by Prostate Cancer UK, The Institute of Cancer Research, Everyman Campaign, National Cancer Research Network UK, National Cancer Research Institute, NIHR Cambridge Biomedical Research Centre and the NIHR Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust.

A family history of cancer and genetic variants that might be inherited appear to be important risk factors for Black men diagnosed with early-onset prostate cancer, a study has found. A family history of cancer and genetic variants that might be inherited appear to be important risk factors for Black men diagnosed with early-onset prostate cancer, a study involving Duke Health researchers has found. Kathleen Cooney, M.D., chair of the Duke Department of Medicine, is the senior author of the study appearing online on Nov. 29 in the journal JCO Precision Oncology. Genetic studies usually recruit non-Hispanic white men, despite data showing that Black men are disproportionately affected by prostate cancer and more than twice as likely to die from the disease compared to their white counterparts. Researchers looked to address this health disparity by identifying genetic variants in Black patients diagnosed with early-onset prostate cancer. They sequenced germline DNA of 743 Black men diagnosed with prostate cancer at 62 years old or younger. This is DNA found in the men's sperm cells, meaning it would contain genetic changes that could be passed on to a child. The focus was on DNA damage repair genes and HOXB13, a gene Cooney's research team found to be associated with hereditary prostate cancer in white men. Researchers identified 26 variants in 14 genes that could cause disease among 30 men, approximately 4% of the patients studied. "We completed sequencing at Duke and our results reveal that men who had certain genetic variants were more likely to have a close relative diagnosed with cancer, have a higher prostate-specific antigen at time of diagnosis, and have more severe cases," Cooney said. "We need to take a closer look at genetic associations to learn more about the susceptibility Black men have to developing prostate cancer," Cooney said. "This could potentially reduce health disparities." The reason for poor outcomes among Black men diagnosed with prostate cancer includes both biological and societal causes, such as access to health care. Data from a previous study reveals genetic make-up may account for up to 40% of all prostate cancer cases. "November is Men's Health Awareness Month and it's our hope that these findings help Black men become more aware of their susceptibility to early-onset prostate cancer," Cooney said. "If men know they have a family history of cancer, it's important to talk to a doctor and consider genetic testing. If they end up having a mutation, they're encouraged to have cancer screenings earlier and more frequently." Additional authors of the study include Matthew Trendowski, Christopher Sample, Tara Baird, Azita Sadeghpour, David Moon, Julie Ruterbusch, and Jennifer Beebe-Dimmer. The study received funding support from the Department of Defense (W81XWH-16-1-0713) and the National Institutes of Health (3T32 HG008955-04S1).