Table 1. Characteristics of included studies [CGs use and cancer risk].
| Study | Year | Country | Drug | Study Design | Size of Study Sample | # of Cancer Cases | Years of Cancer Diagnosis1 | RR (95% CI) | Adjustments in Study Analysis |
|---|---|---|---|---|---|---|---|---|---|
| Risk of Breast Cancer | |||||||||
| Aromaa | 1976 | Finland | Digitalis | Case Control | 218 | 109 | 1973 | 1.33 (0.73–2.48) | None. |
| Danielson | 1982 | United States |
Digitalis | Cohort | - | 302 | 1977–1980 | 1.3 (0.7–2.2) 90% CI |
Age. |
| Friedman | 1984 | United States | Digitalis | Cohort | 143574 | 20 | 1969–1980 | 1.21 (0.78–1.88) | SMR of 10-year age interval. |
| Haux | 2001 | Norway | Digitoxin | Cohort | 5026 | 57 | 1986–1996 | 1.25 (0.95–1.62) | SIR of year of birth and age. |
| Ahern | 2008 | Denmark | Digoxin | Case Control | 61251 | 5,565 | 1991–2007 | 1.30 (1.14–1.48) | Age, residence, HRT, anticoagulants, aspirin and NSAIDs. |
| Biggar | 2011 | Denmark | Digoxin | Cohort | 2,116,029 | 49,016 | 1995–2008 | 1.39 (1.32–1.46) | Attained age and calendar period. |
| Hartz | 2013 | United States | Digitalis | Cohort | 147,202 | - | (1993–1998) + median 8 years follow up |
1.46 (1.24–1.72) | Age, race, and the type of study from which data were obtained. |
| Ahern | 2014 | United States | Digoxin | Cohort | 74,970 | 4,576 | 1994–2010 | 1.40 (1.18–1.65) | Age, height, BMI, age at menarche, age at menopause, alcohol, age at first birth, parity, use of postmenopausal hormones, family history of breast cancer, personal history of benign breast disease, screening mammogram, aspirin, ibuprofen, CLDs and tamoxifen use for breast cancer prevention. |
| Couraud [34] | 2014 | United Kingdom | Digoxin | Case Control | 9838 | 898 | 1988–2012 | 1.07 (0.90–1.26) | Smoking status, BMI, CG-related indications, HRT and estrogen-based contraceptive drug use, statins, aspirin, oral anticoagulants and antiplatelets, NSAIDs, anti-hypertensive drugs, and anti-diabetic drugs. |
| Risk of Prostate Cancer | |||||||||
| Friedman | 1989 | United States | Digitalis | Cohort | 143574 | 43 | 1969–1980 | 1.48 (1.1–2.0) | SMR of 10-year age interval. |
| Haux | 2001 | Norway | Digitoxin | Cohort | 4245 | 108 | 1986–1996 | 1.25 (1.03–1.50) | SIR of year of birth and age. |
| Platz | 2011 | United States | Digoxin | Cohort | 47,884 | 5002 | 1986–2006 | 0.76 (0.60–0.95) | Age, calendar year race, current BMI, BMI at 21, height, family history of prostate cancer, smoking, physical activity, diabetes mellitus, daily caloric intake, linolenic acid, calcium, bacon, fish, tomato sauce use of a vitamin E supplement, use of CLDs, aspirin, ibuprofen, furosemide diuretics, BBs, CCBs, anti-hypertensives, and anti-arrhythmics. |
| Wright | 2014 | United States | Digoxin | Case Control | 1943 | 1001 | 2002–2005 | 0.58 (0.30–1.10) | Age, race, family history of prostate cancer, PSA screening history. ACEIs, diuretics, statins and aspirin. |
| Kaapu | 2015 | Finland | Digoxin | Case Control | 49314 | 24,657 | 1995–2002 | 0.96 (0.90–1.02) | Age, use of antihypertensive drugs, CLDs, antidiabetic drugs, NSAIDs, 5a reductase inhibitors and alpha-blockers. |
| Kaapu | 2016 | Finland | Digoxin | Cohort | 78,615 | 6,639 | 1996–2012 | 1.01(0.87–1.16) | Age, screening trial arm, CLDs, antidiabetic and antihypertensive drugs, aspirin, NSAIDs, 5alpha-reductase inhibitors and alpha-blockers. |
| Risk of Colorectal Cancer | |||||||||
| Friedman | 1984 | United States | Digitalis | Cohort | 143574 | 35 | 1969–1980 | 1.46 (1.05–2.04) | SMR of sex and 10-year age interval. |
| Friedman | 1998 | United States | Digitalis | Case Control | 4403 | 1993 | 1991–1994 | 1.1 (0.8–1.5) | Age, sex, race, family history of colon cancer, BMI, daily intake of calories, fibers, calcium, physical activity, cigarette smoking and alcohol use. |
| Haux | 2001 | Norway | Digitoxin | Cohort | 9271 |
127 | 1986–1996 | 1.29 (1.06–1.51) | SIR of year of birth, age and sex. |
| Boursi | 2014 | United Kingdom | Digoxin | Case Control | 103044 | 20,990 | 1995–2013 | 1.52 (1.40–1.65) | BMI, alcoholism, smoking history, diabetes mellitus, heart disease, chronic NSAIDs use and previous screening colonoscopies |
| Risk of Lung Cancer | |||||||||
| Friedman | 1989 | United Sates | Digitalis | Cohort | 143574 | 56 | 1969–1984 | 1.65 (1.23–2.14) | SMR of sex and 10-year age interval. |
| Haux | 2001 | Norway | Digitoxin | Cohort | 9271 |
63 | 1986–1996 | 1.35 (1.04–1.74) | SIR of year of birth, age and sex. |
| Couraud [35] | 2014 | United Kingdom | Digoxin Lanatoside Digitoxin |
Case Control | 13557 | 1237 | 1988–2012 | 1.09 (0.94–1.26) | Smoking, BMI indication of CG use alcohol use, history of tobacco-related conditions, history of lung diseases, factors associated with sexual hormonal disorders, use of statins, aspirin, oral anticoagulants and antiplatelet, NSAIDs, diuretics spironolactone, CCBs, ARBs, ACEIs, BBs, oral bisphosphonates, metformin, sulfonylureas, insulins, thiazolidinediones, and amiodarone. |
| Risk of Male Breast Cancer | |||||||||
| Lenfant-Pejovic | 1990 | France Switzer land |
Digitalis | Case Control | 346 | 91 | 1975–1988 | 4.1 (1.4–12.4) | None. |
| Ewertz | 2001 | Denmark Norway Sweden |
Digoxin | Case Control | 624 | 156 | 1987–1991 | 1.91(1.05–3.49) | None. |
| Casagrande | 1988 | United States | Digitalis Digoxin |
Case Control | 146 | 73 | 1978–1985 | 0.37(0.11–1.22) | None. |
| Risk of Brain Cancer | |||||||||
| Boursi | 2016 | United Kingdom | Digoxin | Case Control | 5329 | 1076 | 1995–2013 | Glioblastoma: 0.80 (0.40–1.59) |
Obesity, BMI, smoking, diabetes and cardiovascular disease |
| Seliger |
2016 | United Kingdom | CG | Case Control | 22055 | 2005 | 1995–2012 | Glioma: 0.47 (0.27–0.81) Glioblastoma: 0.74(0.36–1.55) |
BMI, smoking, ACEIs, BBs, diuretics, anti-arrhythmics other than CG, ARBs, CCBs, statins, aspirin, thrombocyte inhibitors, vitamin K antagonists, coronary vasodilators, nitrates, insulin, and oral antidiabetics |
| Risk of Uterine Cancer | |||||||||
|
Biggar |
2012 |
Denmark |
Digoxin |
Cohort |
2,116,029 |
8,124 | 1995–2008 | 1.48, (1.32–1.65) |
Age and calendar time. |
| Risk of Ovarian Cancer | |||||||||
| 7,124 | 1995–2008 | 1.06 (0.92–1.22) | |||||||
| Risk of Cervical Cancer | |||||||||
| 5,001 | 1995–2008 | 1.00 (0.79–1.25) | |||||||
| Risk of Leukemia and Lymphoma | |||||||||
|
Haux |
2001 |
Norway |
Digitoxin |
Cohort |
9271 |
53 | 1986–1996 | 1.41 (1.06–1.85) |
SIR of year of birth, age and sex. |
| Risk of Kidney and Urinary Cancers | |||||||||
| 59 | 1986–1996 | 1.14 (0.87–1.47) | |||||||
| Risk of Melanoma and Skin Cancers | |||||||||
| 61 | 1986–1996 | 1.23 (0.94–1.58) | |||||||
| Risk of Uterine Cancer Non-Hodgkin’s Lymphoma | |||||||||
| Bernstein | 1992 | United States |
Digitalis | Case Control | 1238 | 619 | 1979–1982 | 1.55 (0.99–2.43) |
None. |
1Duration in which cancer cases were diagnosed.
*Abbreviations: (ACEIs) Angiotensin-Converting-Enzyme Inhibitors, (ARBs) Angiotensin Receptor Blockers, (BBs) Beta Blockers, (BMI) Body Mass Index, (CCBs) Calcium Channel Blockers, (CG) Cardiac Glycosides, (CLDs) Cholesterol-Lowering Drugs, (HRT) Hormone Replacement Therapy, (NSAIDs) Non-Steroidal Anti-Inflammatory Drugs, (PSA) Prostate-Specific Antigen, (SIR) Standardized Incidence Ratio, (SMR) Standardized Morbidity Ratio.