Cancers and Deaths

Baseline SELECT SELECT CFU

Medical history, limited physical exam, Ht/Wt, demographics

Yes

Quality of Life (SF-36) On subset

Family history of cancer Prostate, lung, colon

PSA Participant report or done at site

Diet and supplement use Yes

Follow-up

Frequency Every 6 months Annual

Medical events/side effects Yes Cancer diagnoses, diabetes

Medications Extensive Finasteride, statins, aspirin, NSAIDs

Prostate health Yes Prostate cancer treatments

PSA and DRE Annual; Participant report or done at site

PSA (self-reported by men with prostate cancer)

Updated supplement use Annual

Adherence assessment Yes

Updated smoking history Annual Yes

Weight Annual Yes

Quality of Life (SF-36) On subset

Cancer site Total

Total with some source

documentation

Total with a baseline plasma

specimen

Total with a Year 5 plasma

specimen2

Total with Buffy Coat available

Prostate1 2,494 2,012 2,321 1,710 2,370 Bladder 249 229 227 156 230 Colorectal 323 298 293 172 298 Lung 381 352 349 139 351 Melanoma 333 311 308 254 315 Pancreatic 118 100 104 29 104 Renal 110 101 103 76 105 Other 807 730 729 414 743

Non-cancers 30,948 N/A 27,934 19,424 28,406

1During SELECT or CFU; 2Includes final sample for men with prostate cancer

Tissue N (%)

Total participant events* 2,836

Archive (per event) Any material 1,422 (50.1%)

Unstained slides 1,335 (47.1%)

Paraffin blocks 61 ( 2.2%)

Paraffin blocks Cancer, biopsy 21 Non-cancer, biopsy 74 Prostatectomy 153

TURP 2

Slides Total H&E slides 5,759 Total unstained slides 18,388

* Event = Biopsy, TURP, prostatectomy

Blood

PSA Reported by site

Cholesterol Case-cohort, Adherence subset

Tocopherols Case-cohort, Adherence subset

Carotenoids Case-cohort

Fatty acids Case-cohort subset (all high grade cases, all prostate cancers through 2007)

Selenium Case-cohort

Vitamin D Case-cohort

Genotyping

Various panels Case-cohort, all African Americans

Background

Baseline Characteristic

SELECT (n=35,533) CFU (n=17,747) N (%) N (%)

Age at baseline (years) Median 62 62 50 - 54 1,728 (4.9) 633 (3.6)

55 - 59 11,341 (31.9) 5,933 (33.4) 60 - 64 9,281 (26.1) 4,866 (27.4) 65 - 69 6,917 (19.5) 3,514 (19.8)

≥ 70 6,266 (17.6) 2,801 (15.8)

Current age (years) Median 72 72 58 - 69 12,334 (35.1) 6,385 (36.0)

70 -79 14,980 (42.2) 8,295 (46.7) 80 - 89 4,726 (13.3) 2,650 (14.9) ≥ 90 324 (0.9) 129 (0.7)

N/A Deceased 3,169 (8.9) 288 (1.6)

Race/Ethnicity White 27,592 (77.7) 14,753 (83.1) African American (AA) 4,907 (13.8) 1,990 (11.2) Hispanic (not AA) 1,945 (5.5) 555 (3.1) Hispanic (AA) 356 (1.0) 71 (0.4) Other 732 (2.1) 378 (2.1)

PSA (ng/ml) Median 1.1 1.1 0 - 1.0 17,177 (48.3) 8,436 (47.5)

1.0 - 2.0 10,895 (30.7) 5,579 (31.4) 2.1 - 3.0 4,815 (13.6) 2,410 (13.6)

3.0 - <4.0 2,646 (7.4) 1,322 (7.4)

Prostate Cancer in 1st Degree Relative Yes 6,609 (18.6) 3,453 (19.5)

Body Mass Index (BMI) Normal (< 25) 7,129 (20.1) 3,571 (20.1) Overweight (25 - <30) 16,991 (47.8) 8,692 (49.0) Obese (≥30) 11,198 (31.5) 5,408 (30.5)

Education ≤ High school or GED 8,100 (22.8) 2,854 (16.1) Some college/vocational 9,451 (26.6) 4,634 (26.1) ≥ College graduate 17,613 (49.6) 10,130 (57.1)

Cigarette smoking Never 15,107 (42.5) 8,158 (46.0) Former 17,333 (48.8) 8,524 (48.0)

Current 2,898 (8.2) 1,010 (5.7)

Numbers of unknowns are not presented

The Selenium and Vitamin E Cancer Prevention Trial (SELECT), conducted by SWOG at 427 study sites, recruited over 35,500 healthy men, age 55 and over (50 if African-American), from the United States, Canada and Puerto Rico to evaluate if selenium (200 mcg/day) or vitamin E (400 IU/day) alone or in combination would prevent prostate cancer. Prostate cancer detection was based on community standards and confirmed by central pathology review. Accrual began in 2001 and was completed in 2004. The intervention was stopped in 2008 due to lack of benefit of the study supplements on prostate cancer incidence. An updated analysis in 2011 showed a 17% increase in risk of prostate cancer in the vitamin E alone arm. Study sites were closed and over 17,700 participants agreed to annual Centralized Follow-up (CFU) by mail, phone and secure web access. SELECT has a robust repository of biologic specimens, data and a large number of dedicated participants.

Research Opportunities from SELECT, a Long Term Prevention Study: Biospecimens, Data and Participants

Monica Yee1, Phyllis Goodman2, Karen Anderson1, Jo Ann Hartline1, John Crowley1, Eric Klein3

Population

Biospecimen and Data Requests

Existing Clinical Data Biorepository: Available Serum and Tissue

1 SWOG Statistical Center at Cancer Research And Biostatistics (CRAB), Seattle, WA, 2 SWOG Statistical Center at Fred Hutchinson Cancer Research Center, Seattle, WA, 3 Glickman Urological and Kidney Institute, Cleveland, OH

Specimen Type Baseline

6 Months 1

Year 2

Years 4

Years 5

Years 6

Years

Toenail 31,196 Blood 29,381 2,174 2,190 1,949 1,807 20,972 1,057

Case-Cohort Study

SELECT is in its thirteenth year and continues collecting annual health and contact information for over 17,000 participants in Centralized Follow-up (CFU). Over 1,800 SELECT participants also participated in the Prostate Cancer Prevention Trial (PCPT) which preceded SELECT. Over 1,100 of the PCPT participants continued on CFU. Some CFU participants joined PCPT as early as 1994 resulting in over 20 years of SWOG clinical trial participation. Many of the participants also consented to participate in one or more of the four SELECT ancillary studies. The primary reason participants joined SELECT were altruistic reasons such as “it may help others in the future,” “it may prevent prostate cancer” and “it makes me proud to be part of a study.” Participants often ask if there are other research opportunities for their participation. SELECT has consents on file and current contact information for those who have agreed to be contacted for future studies. CFU participants are geographically located in all areas of the United States, including Puerto Rico and Canada, as demonstrated below. There is potential for researchers to approach a large number of dedicated participants to conduct surveys or recruit for other clinical trial research.

A case-cohort study was imbedded within SELECT to investigate hypotheses based on biomarkers. A case-cohort of 3,404 men, including 1,856 men (of the 2,494 diagnosed) with prostate cancer have had their baseline plasma nutrient levels (α-tocopherol, γ-tocopherol, cholesterol, selenium (in process), vitamin D, carotenoids) and toenail selenium measured, as well as DNA extracted. All incident prostate cancer cases and a subset of non-cases were chosen so that the same cohort can be used to analyze associations in addition to prostate cancer of other endpoints of interest such as other cancers, Alzheimer’s disease, respiratory function and macular degeneration. Other research areas could also utilize this case-cohort structure which will lead to efficiencies in study design. A nested case-control study could also be designed using the SELECT cohort depending on the research question of interest.

Over 100,000 biologic specimens are available to the research community to answer questions about cancer and other chronic diseases. Data from SELECT are also available to conduct other analyses. Investigators within SWOG as well as external investigators are welcome to submit a proposal for consideration. The application process and more information about the SELECT repository is described on the SWOG website at:

http://swog.org/Visitors/TranslationalMed.asp

Existing Biologic Measures

Potential Participants for Epidemiologic Research

ACKNOWLEDGEMENT SUPPORT: SELECT is supported by grant CA37429 and SELECT cohort UM1 grant CA182883 from the National Cancer Institute. TRIAL INFORMATION: clinicaltrials.gov Identifier: NCT00006392

Other cancers were reported by the participant to study site staff. Source documentation was to be submitted to the Statistical Center for storage. Upon the interest of an investigator, these source documents can be reviewed and coded. Sites were asked to collect source documentation for all deaths for coding cause of death on study forms but were not asked to submit the source documentation. A Social Security Death Index (SSDI) search was performed in 2012.

Completed and Ongoing Areas of Research

Additional studies • Geographic distribution of

selenium • Contributor to GWAS projects • Association of heavy metals with

outcomes

Prostate cancer risk and dietary factors Imbedded ancillary studies on • Alzheimer’s disease • Age-related macular degeneration and

cataracts • Pulmonary function • Colorectal adenomas and colorectal

cancer

Prostate Cancers

Biopsies and transurethral resections of the prostate (TURPs) were reviewed centrally by the central Pathology Diagnostic Laboratory (PDL) for confirmation of disease and Gleason scoring. If tissue was not submitted for review to the PDL, Gleason Score was abstracted from the local biopsy pathology report.

# Prostate Cancers

Gleason Score

Total 2-6 7- 10 Unk Placebo 8,856 596 301 138 157

Selenium 8,910 642 300 173 169

Vitamin E 8,904 687 330 164 193

Se + Vit E 8,863 604 289 169 146

Cancer N Any 4,815 Prostate 2,494

Bladder 249 Colorectal 323 Lung 381 Melanoma 333 Pancreatic 118 Renal 110 Other primary 807

Deaths Total 3,071

Prostate cancer 12

Other cancer 723

Cardiovascular 746

Other 671

Unknown/SSDI* 919

* A National Death Index search is planned to ascertain cause of death

Other Cancers and Deaths

Biospecimens were collected and stored on all SELECT participants. Specimens included baseline toenail and blood and Year 5 blood on all; serial blood samples were collected on a 7% adherence cohort. Bloods were collected at least 3 hours after a meal (i.e., a modified fast), and the date and time of blood collection, as well as time since last meal, was recorded. Plasma was divided into up to twenty 0.5 ml aliquots and frozen at -70oC. Buffy coat WBC’s were collected and separated into 3-4 aliquots: in two aliquots DMSO was added before freezing at a controlled rate in in vapor-phase liquid nitrogen; 1-2 aliquots were frozen at -70oC for later DNA extraction. Two large aliquots (4.5 ml) of RBC’s were also stored (-70oC). Tissue from biopsy, prostatectomy and transurethral resection specimens was obtained at study sites using the standard procedures in place at each site. All sites submitted material in neutral buffered formalin fixative for processing and mounting onto glass slides by local pathology laboratories. After the slides were reviewed by the local pathologists, the diagnostic or representative slides were shipped to the Core Pathology Lab for centralized review. Sites were also encouraged to send additional unstained sections or blocks of the diagnostic tissue to the Core Lab for archiving.