Table 1.
Characteristics of the 8 prospective studies included in the meta-analysis examining the associations between endogenous sex hormones and the risk of colorectal cancer risk
| Study | Country | Study design | Length of follow-up (years)a | Population | Cases | Controls | Age (years)a | BMI (kg/m^2)a | Exposure(s) of interest | Method of assessment | Adjustments |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NYUWHS (Clendenen, T. V., 2009) | USA | Nested case–control | From 1985 to 2003 | Post-menopausal women | 148 | 293 | Cases: 60.4; Controls: 60.4 | Case: 25.6; Control: 24.7 | Estradiol; SHBG |
Estradiol; RIA following organic extraction and celite chromatography (LLOQ = 2 pg/mL); SHBG: Two-site immunometric chemiluminescent assay on an IMMULITE 2000 instrument (LLOQ = 2 nmol/L) |
Age at enrolment, date of blood donation, BMI |
| Copenhagen City Heart Study (Orsted, D. D., 2014) | Denmark | Cohort | 22 | Men; Womenb | Men: 185; Women: 84 | Men: 4243; Women: 4217 | Men: 58.0; Women: 57.0 | Men: 25.6; Women: 24.0 | Testosterone | Testosterone: Immunochemically using the ADVIA (reportable range of the assay 0.35–260 nmol/L) | Smoking status, cumulative smoking, BMI, alcohol consumption, level of education, and level of income. In women also adjusted for parity, menopausal status, oral contraceptive use, and hormone replacement therapy |
| WHI-CT (Murphy, N., 2015) | UK | Nested case–control | From 1993–98 to 2008 | Post-menopausal women | 401 | 802 | Case: 66.0; Control: 66.0 |
Case: 28.5; Control: 28.4 |
Estradiol; SHBG |
Estradiol: RIA following organic extraction and celite chromatography (LLOQ = 2 pg/mL); SHBG: RIA following organic extraction and celite chromatography (LLOQ = 10 pg/mL) |
WC, alcohol consumption, history of CRC, physical activity, smoking status, and NSAID use |
| Busselton Health Study (Chan, Y. X., 2018) | Australia | Cohort | 20 | Men | 48 | 1526 | Overall: 51.1 | Overall: 26.7 | Testosterone; Estradiol; SHBG |
Testosterone: single LC–MS/MS (CV of 8.6% at 5.3 nmol/L and 7.9% at 26.9 nmol/L; Estradiol: Single LC–MS/MS (CV of 14.5% at 73 pmol/L and 9.9% at 279 pmol/L.); SHBG: Two-site immunometric chemiluminescent assay on an IMMULITE 2000 instrument (CV of 3.4% at 39.4 nmol/L) |
Age, marital status, occupation, smoking, alcohol consumption, leisure time physical activity, BMI and diabetes |
| HIMS (Chan, Y. X., 2017) | Australia | Cohort | 9 | Men | 137 | 3436 | Case: 77.9; Control: 76.9 | Case: 26.4; Control: 26.5 | Testosterone; Estradiol; SHBG |
Testosterone: single LC–MS/MS run (CV of < 6% for T levels of > 0.4 nmol/l); Estradiol: single LC–MS/MS run (CV of < 8% for E2 levels of > 25 pmol/l); SHBG: chemiluminescent immunoassays (CV < 7%) |
Age, BMI, smoking status, physical activity, duration of smoking, smoking exposure, alcohol, diabetes, HDL, TG, and history of cancer |
| JPHC (Mori, N., 2019) | Japan | Nested case–control | 12 | Post-menopausal women | 185 | 361 | Case: 60.0; Control: 59.8 | Case: 23.8 Control: 23.5 | Testosterone; Estradiol; SHBG |
Testosterone: electrochemiluminescence (LLOQ < 0.226 ng/ml); Estradiol: electrochemiluminescence (LLOQ < 0.039 ng/ml); SHBG: chemiluminescence enzyme immunoassay; |
BMI, smoking status, alcohol consumption, physical activity |
| NHS, WHS, HPFS, PHSII (Lin, J. H., 2013) | USA | Nested case–control | From (NHS:1989–90, WHS:1992, HPFS:1993–94, PHSII: 1986) to 2008 |
Men; Post-menopausal women |
Men: 439; Women: 293 | Men: 719; Women: 437 | Case: 67.2; Control: 67.7 | Case: 26.2; Control: 25.5 | Testosterone; Estradiol; SHBG |
Testosterone: competitive electrochemiluminescence immunoassay; Estradiol: turbulent flow liquid chromatography tandem mass spectrometry; SHBG: competitive electrochemiluminescence immunoassay; Mean intra-assay CVs 4%–7% in men and 3%–7% in women |
Age, fasting status, hour at blood draw, smoking, alcohol intake, history of cancer, physical activity, history of polyps, and screening examination, BMI and C-peptide |
| WHI-OS (Gunter, M. J., 2008) | USA | Case-Cohort | 6 (subcohort) | Post-menopausal women | 438 | 809 | Case: 65.9 Subcohort: 62.8 | Case: 27.56; Subcohort: 27.07 | Estradiol | Estradiol: Immunodiagnostic Assay | Age, smoking, ethnicity, family history of CRC, history of colonoscopy, physical activity, use of NSAIDs, and alcohol consumption |
aData are presented as mean or median values
bAt baseline approximately 52% of women were post-menopausal and we expect that the majority of women would have been be post-menopausal at the time of cancer diagnosis, though this information was not reported in the paper
NYUWHS New York University Women’s Health Study, WHI Women’s Health Initiative, CT Clinical trial, OS Observational study, CV coefficient of variation, HIMS Health in Men Study, JPHC Japan Public Health Center-based Prospective Study, NHS Nurses’ Health Study, WHS Women’s Health Study, HPFS Health Professional Follow-up Study, PHSII Physicians’ Health Study II, SHBG Sex hormone binding globulin, BMI: Body mass index, LLOQ lower limit of quantitation, WC Waist-circumference, CRC Colorectal cancer, HDL High-density lipoprotein, TG Triglycerides, NSAID Nonsteroidal anti-inflammatory drugs, RIA Radioimmunoassay, LC liquid chromatography, MS mass spectrometry, ng Nano-grammar, mL milliliter, nmol nanomole, L Litre, pmol picomol