Studies investigating polymorphisms in the IGF-I, IGF-II, and IGFBP-3 genes in relation to measurements of serum levels of their protein products
| Reference . | Study details . | Study population . | Exclusion criteria . | Allele frequency* . | Variables matched or adjusted for . | Arithmetic mean*†‡ (SE or 95% CI), ng/mL . | Analysis . | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| IGF-I (CA 5′ STR) | ||||||||||||||
| Rosen et al. (55) | Study period NA, Richmond, VA. Observational study of hormonal determinants of bone mineral density | 30 men, age mean 48.0 y | Conditions and medications known to affect serum IGF-I or bone density | CA19: 59% for all three combined. Ethnicity Caucasian. HWE NA | None for main analysis. Some analysis stratified by gender | 129 (7) vs 154 (9); P = 0.03 in 59 men and 57 women combined | 19/19 vs (19/− and −/−) | |||||||
| Study period NA, Maine, randomized controlled trial of calcium supplementation | 37 postmenopausal women, age mean 72.3 y | 158.6 (9.0) vs 188.8 (8.6); P = 0.02 in men only (n = 89) | 19/19 vs (19/− and −/−) | |||||||||||
| Study period NA, location NA. Cardiology referrals | 59 men, 20 women, age mean 58.6 y | “No difference” between 19/− and any other genotype | ||||||||||||
| Jernström et al. (58) | Study period NA, Toronto, Canada. Healthy volunteers | 311 women, age mean 25.4 y (range 17-35) | Non-Caucasian, history of pregnancy/cancer/diabetes, hysterectomy, current estrogen non–oral contraceptive use | CA19: Allele frequency or genotypes for entire group NA. From graphs, −/− (n = 26) and “one or two 19” alleles (n = 263; 309 total). Ethnicity Caucasian. HWE NA | Age, estrogen dose (in oral contraceptive users) | 264 vs 315; P = 0.025 in oral contraceptive users | (19/19 and 19/−) vs −/− | |||||||
| Effect only given stratified by oral contraceptive use | 305 vs 287 in non–oral contraceptive users (approximate figures from graphs, exact figures NA) | (19/19 and 19/−) vs −/− | ||||||||||||
| Test for interaction between genotype and oral contraceptive use P = 0.04 | ||||||||||||||
| Jernström et al. (56) | Study period NA, Toronto, Canada. Healthy volunteers | 507 women, age mean NA (range, 17-35 y) | Mixed ethnicity, history of pregnancy/cancer/diabetes, hysterectomy, current estrogen non–oral contraceptive use | CA19: White§ 70.2%, Black 37.8%, Asian 40.8%, Indian/Pakistani 56.0%. Ethnicity 329 White, 78 Black, 71 Asian, 25 Indian/Pakistani. HWE NA | Age, estrogen dose (in oral contraceptive users), not ethnicity | 266 vs 338; P = 0.00007 in oral contraceptive users | (19/19 and 19/−) vs −/− | |||||||
| Effect only given stratified by oral contraceptive use | 305 vs 312 in non–oral contraceptive users (approximate figures from graphs, exact figures NA) | (19/19 and 19/−) vs −/− | ||||||||||||
| Test for interaction between genotype and oral contraceptive use P = 0.002 | ||||||||||||||
| Vaessen et al. (59) | 1990-1993, Rotterdam, the Netherlands. Population-based cohort (myocardial infarction cases) | 55 men, 95 women. 50 each of 19/19, 19/−, and −/−, age mean 60.7 y | Age <55 or >75 y, medication for non-insulin-dependent diabetes mellitus/hormone conditions | CA19: 67.6%. Ethnicity Caucasian. HWE P = 0.76 | Age | 157.7 vs 128.5 (geometric means) | 19/19 vs −/− | |||||||
| 29.2 (−46.2 to −10.0; P = 0.003) | Mean difference | |||||||||||||
| Allen et al. (62) | 1994-1997, Oxford, United Kingdom. European Prospective Investigation into Cancer and Nutrition | 660 men, age mean 47 y (range 20-78) | Cancer history, certain medications, estimated energy intake <3.1 or >18.4 mJ/d | CA19: 64.2%. Ethnicity Caucasian. HWE P = 0.95 | Age, body mass index dietary group, smoking, days between blood collection and processing | 151.5 (148.5-156.9) vs 150.8 (146.2-155.4) vs 150.0 (140.8-158.5; Plinear trend = 0.66) | 19/19 vs 19/− vs −/− | |||||||
| Also tested 19/19 and 19/− vs −/− (NS) and repeat length vs serum levels | ||||||||||||||
| Frayling et al. (64) | 1997-1999, Barry and Caerphilly, Wales. Adult offspring of mothers in randomized controlled trial of milk token supplementation | 342 men, 298 women, age 25 y (all) | Insulin-dependent diabetes mellitus | CA19: 62.9%. Ethnicity Caucasian. HWE P = 0.99 | Age, gender | 133.2 (127.2-139.5) vs 143.5 (137.6-149.6) vs 142.8 (133.4-152.5; Plinear trend = 0.01) | 19/19 vs 19/− vs −/− | |||||||
| Giovannucci et al. (65) | 1989-Jun 1994, Nurses' Healthy Study cohort (colorectal adenoma cases) | 202 cases, 202 controls, age mean NA | Family history of colorectal cancer, history of cancer or adenoma | CA19: 61.8%. Ethnicity NA. HWE NA | Age, month of/fasting status at blood draw, year of (and indications for) endoscopy | 168.6 vs 167.7 (P = 0.88), cases and controls combined | 19/19 vs (19/− and −/−) | |||||||
| 168.6 vs 166.4 (P = 0.76) cases and controls combined | 19/19 vs 19/20 | |||||||||||||
| (figures for controls only NA) | ||||||||||||||
| Kim et al. (63)∥ | Study period NA, Seoul, Korea. Attending menopause clinic for bone mineral density measurement | 229 postmenopausal women, age mean NA (range 45-75 y) | Premenopausal, bilateral oophorectomy, hepatic/renal disease, medications affecting bone metabolism | CA19: 14.3%. Ethnicity Korean. HWE NA | Age, body mass index, years since menopause | 140 vs 150 vs 160 (P > 0.05; approximate figures from graphs, exact figures NA) | 19/19 vs 19/− vs −/− | |||||||
| Higher levels in women with 20/20 genotype (P < 0.005) | 20/20 vs 20/− vs −/− | |||||||||||||
| Missmer et al. (61) | 1989-Jun 1994, Nurses' Health Study cohort | 418 control women, age mean NA | Cancer history | CA19: 63.3% (n = 622). Ethnicity all but eight women (cases + controls) Caucasian. HWE NA | Age, HRT use, menopausal status, time of/fasting status at blood draw | 173 vs 146 (P = 0.005) all women combined | 19/19 vs 19/− vs −/− | |||||||
| Stratified by fasting status, time of blood draw, HRT use | 183 vs 175 vs 155 (P = 0.10) premenopausal women | 19/19 vs −/− | ||||||||||||
| Values NA (P = 0.78) premenopausal women | 19/19 vs 19/− | |||||||||||||
| DeLellis et al. (66) | 1993-1996, Hawaii and Los Angeles, Multiethnic cohort | 230 postmenopausal women, age mean NA (range 45-75 y) | Cancer history, HRT use in previous 2 wk | CA19: African American 40.8%, Japanese American 39.0%, non-Latino White 69.1%, Latino White 64.0%. Genotypes 19/19 vs 19/− vs −/− differed “significantly” between ethnic groups. Ethnicity 65 African American, 50 Japanese American, 47 non-Latino White, 68 Latino White. HWE no evidence for departure (P = NA) | Crude and age-adjusted estimates presented | African American 150 (106-194) vs 166 (142-190) vs 150 (121-180; P ≥ 0.05) | 19/19 vs 19/− vs −/− | |||||||
| Japanese American 146 (101-190) vs 148 (130-167) vs 144 (119-169; P > 0.05) | 19/19 vs 19/− vs −/− | |||||||||||||
| Non-Latino White 146 (125-167) vs 142 (121-162) vs 160 (104-216; P > 0.05) | 19/19 vs 19/− vs −/− | |||||||||||||
| Latino White 118 (93-142) vs 126 (101-151) vs 149 (107-192; P > 0.05) | 19/19 vs 19/− vs −/− | |||||||||||||
| Kato et al. (57) | 1998-1999, Louisiana, Prostate screening program, breast clinic attendees, hospital employees | 60 men, age mean NA (range 48-86). 53 women, age mean NA (range 22-73) | Diabetes, cancer history, “any other serious condition” | CA19: Caucasians 30.4%, African Americans 18.4%. Frequency of 19 allele higher in Caucasian (P = 0.04). Ethnicity 56 Caucasian, 57 African American. HWE tested in all ethnic groups combined (P = 0.219) | Age, ethnicity matching to prostate/breast cancer cases: (a) hormone use, age, smoking, log height (African American women); (b) hormone use and age <40 (Caucasian women), (c) log-height, log body mass index (African American men) NA (Caucasian men) | African American women 110.8 vs 95.5 (P = 0.35) | 19/− vs −/− | |||||||
| Caucasian women 88.2 vs 92.3 (P = 0.79) | 19/− vs −/− | |||||||||||||
| African American men 106.9 vs 94.9 (P = 0.43) | 19/− vs −/− | |||||||||||||
| Caucasian men 94.8 vs 118.7 (P = 0.091) | 19/− vs −/− | |||||||||||||
| Rietveld et al. (60) | 1990-1993, Rotterdam, the Netherlands. Population-based cohort (myocardial infarction cases) | 80 men, 88 women, age mean 67.4 y | Age <55 or >75 y | CA19: 63.7% for random sample. Ethnicity Caucasian. HWE NA | Age group to myocardial infarction cases, gender, body mass index | 143.8 (134.8-152.8) vs 126.9 (117.9-135.9; P = 0.01). Combined figures for random sample (n = 168) and for those selected on genotype (n = 150) | 19/19 vs −/− | |||||||
| 150 selected on IGF-I genotype (59), age NA | Age <55 or >75 y, diabetes, HRT | |||||||||||||
| IGF-I (intronic STR) | ||||||||||||||
| Arends et al. (70) | Study period NA, location NA. Family-based association study comparing transmission of alleles | 124 children born small for gestational age and their parents, age mean NA | Neonatal complications, endocrine and metabolic disorders (children) | NA (not population-based). Ethnicity 113 Caucasians, 1 Asian, 1 Indo-Mediterranean, 4 mixed | Showed preferential transmission of 191-bp allele (P = 0.02) and lower IGF-I levels in children with this allele. −1.1 vs −0.5 SD scores (P = 0.03) | |||||||||
| IGF-II (A/G ApaI RFLP in 3′ untranslated region) | ||||||||||||||
| O'Dell et al. (73) | Study period NA, Northwick Park, United Kingdom. Northwick Park Heart cohort | 92 men (48 common, 44 rare homozygotes), age mean NA (range 45-65 y) | NA | A 0.28, G 0.72. Ethnicity Caucasian. HWE “applied” | 614.0 ± 124.0 vs 683.3 ± 146.9 (P = 0.01) | GG vs AA | ||||||||
| IGFBP-3 (A/C single nucleotide polymorphism at nucleotide −202) | ||||||||||||||
| Deal et al. (75) | 1982-1995, Physicians' Health Study (colorectal cancer cases) | 478 men (cases and controls), age mean NA (range 40-84 y) | History of cancer, myocardial infarction, stroke, transient ischemic attack, current liver/renal disease, peptic ulcer, gout, vitamin A use, β-carotene supplement at start of study | A 0.46, C 0.54. Ethnicity NA. HWE tested in cases and controls combined | R2 for polymorphism was 0.077 | 3,274 vs 2,753 (SD NA) for controls only | AA vs CC | |||||||
| 3180 vs 3000 vs 2760 in cases and controls combined (approximate figures from graphs, exact figures NA) | AA vs AC vs CC | |||||||||||||
| Jernström et al. (56) | Study period NA, Toronto, Canada. Healthy volunteers | 311 women, age 25.4 y (range 17-35) | Non-Caucasian, ever pregnant, cancer, diabetes, hysterectomy, estrogen non–oral contraceptive use | A 0.47, C 0.53. Ethnicity Caucasian. HWE NA | 4,390 vs 4,130 vs 3,840 | AA vs AC vs CC | ||||||||
| Schernhammer et al. (80) | 1989-Jun 1996, Nurses' Health Study cohort (breast cancer cases) | 943 women (cases and controls), age mean NA | Cancer history | A 0.46, C 0.54 in cases and controls combined. Ethnicity NA. HWE tested in cases and controls combined (P > 0.90) | Age, menopausal status, HRT use, blood draw details. R2 for polymorphism was 0.06 | 4,426 (4,291-4,561) vs 4,060 (3,970-4,150) vs 3,697 (3,581-3,813) in cases and controls combined (Plinear trend < 0.001) | AA vs AC vs CC | |||||||
| Reference . | Study details . | Study population . | Exclusion criteria . | Allele frequency* . | Variables matched or adjusted for . | Arithmetic mean*†‡ (SE or 95% CI), ng/mL . | Analysis . | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| IGF-I (CA 5′ STR) | ||||||||||||||
| Rosen et al. (55) | Study period NA, Richmond, VA. Observational study of hormonal determinants of bone mineral density | 30 men, age mean 48.0 y | Conditions and medications known to affect serum IGF-I or bone density | CA19: 59% for all three combined. Ethnicity Caucasian. HWE NA | None for main analysis. Some analysis stratified by gender | 129 (7) vs 154 (9); P = 0.03 in 59 men and 57 women combined | 19/19 vs (19/− and −/−) | |||||||
| Study period NA, Maine, randomized controlled trial of calcium supplementation | 37 postmenopausal women, age mean 72.3 y | 158.6 (9.0) vs 188.8 (8.6); P = 0.02 in men only (n = 89) | 19/19 vs (19/− and −/−) | |||||||||||
| Study period NA, location NA. Cardiology referrals | 59 men, 20 women, age mean 58.6 y | “No difference” between 19/− and any other genotype | ||||||||||||
| Jernström et al. (58) | Study period NA, Toronto, Canada. Healthy volunteers | 311 women, age mean 25.4 y (range 17-35) | Non-Caucasian, history of pregnancy/cancer/diabetes, hysterectomy, current estrogen non–oral contraceptive use | CA19: Allele frequency or genotypes for entire group NA. From graphs, −/− (n = 26) and “one or two 19” alleles (n = 263; 309 total). Ethnicity Caucasian. HWE NA | Age, estrogen dose (in oral contraceptive users) | 264 vs 315; P = 0.025 in oral contraceptive users | (19/19 and 19/−) vs −/− | |||||||
| Effect only given stratified by oral contraceptive use | 305 vs 287 in non–oral contraceptive users (approximate figures from graphs, exact figures NA) | (19/19 and 19/−) vs −/− | ||||||||||||
| Test for interaction between genotype and oral contraceptive use P = 0.04 | ||||||||||||||
| Jernström et al. (56) | Study period NA, Toronto, Canada. Healthy volunteers | 507 women, age mean NA (range, 17-35 y) | Mixed ethnicity, history of pregnancy/cancer/diabetes, hysterectomy, current estrogen non–oral contraceptive use | CA19: White§ 70.2%, Black 37.8%, Asian 40.8%, Indian/Pakistani 56.0%. Ethnicity 329 White, 78 Black, 71 Asian, 25 Indian/Pakistani. HWE NA | Age, estrogen dose (in oral contraceptive users), not ethnicity | 266 vs 338; P = 0.00007 in oral contraceptive users | (19/19 and 19/−) vs −/− | |||||||
| Effect only given stratified by oral contraceptive use | 305 vs 312 in non–oral contraceptive users (approximate figures from graphs, exact figures NA) | (19/19 and 19/−) vs −/− | ||||||||||||
| Test for interaction between genotype and oral contraceptive use P = 0.002 | ||||||||||||||
| Vaessen et al. (59) | 1990-1993, Rotterdam, the Netherlands. Population-based cohort (myocardial infarction cases) | 55 men, 95 women. 50 each of 19/19, 19/−, and −/−, age mean 60.7 y | Age <55 or >75 y, medication for non-insulin-dependent diabetes mellitus/hormone conditions | CA19: 67.6%. Ethnicity Caucasian. HWE P = 0.76 | Age | 157.7 vs 128.5 (geometric means) | 19/19 vs −/− | |||||||
| 29.2 (−46.2 to −10.0; P = 0.003) | Mean difference | |||||||||||||
| Allen et al. (62) | 1994-1997, Oxford, United Kingdom. European Prospective Investigation into Cancer and Nutrition | 660 men, age mean 47 y (range 20-78) | Cancer history, certain medications, estimated energy intake <3.1 or >18.4 mJ/d | CA19: 64.2%. Ethnicity Caucasian. HWE P = 0.95 | Age, body mass index dietary group, smoking, days between blood collection and processing | 151.5 (148.5-156.9) vs 150.8 (146.2-155.4) vs 150.0 (140.8-158.5; Plinear trend = 0.66) | 19/19 vs 19/− vs −/− | |||||||
| Also tested 19/19 and 19/− vs −/− (NS) and repeat length vs serum levels | ||||||||||||||
| Frayling et al. (64) | 1997-1999, Barry and Caerphilly, Wales. Adult offspring of mothers in randomized controlled trial of milk token supplementation | 342 men, 298 women, age 25 y (all) | Insulin-dependent diabetes mellitus | CA19: 62.9%. Ethnicity Caucasian. HWE P = 0.99 | Age, gender | 133.2 (127.2-139.5) vs 143.5 (137.6-149.6) vs 142.8 (133.4-152.5; Plinear trend = 0.01) | 19/19 vs 19/− vs −/− | |||||||
| Giovannucci et al. (65) | 1989-Jun 1994, Nurses' Healthy Study cohort (colorectal adenoma cases) | 202 cases, 202 controls, age mean NA | Family history of colorectal cancer, history of cancer or adenoma | CA19: 61.8%. Ethnicity NA. HWE NA | Age, month of/fasting status at blood draw, year of (and indications for) endoscopy | 168.6 vs 167.7 (P = 0.88), cases and controls combined | 19/19 vs (19/− and −/−) | |||||||
| 168.6 vs 166.4 (P = 0.76) cases and controls combined | 19/19 vs 19/20 | |||||||||||||
| (figures for controls only NA) | ||||||||||||||
| Kim et al. (63)∥ | Study period NA, Seoul, Korea. Attending menopause clinic for bone mineral density measurement | 229 postmenopausal women, age mean NA (range 45-75 y) | Premenopausal, bilateral oophorectomy, hepatic/renal disease, medications affecting bone metabolism | CA19: 14.3%. Ethnicity Korean. HWE NA | Age, body mass index, years since menopause | 140 vs 150 vs 160 (P > 0.05; approximate figures from graphs, exact figures NA) | 19/19 vs 19/− vs −/− | |||||||
| Higher levels in women with 20/20 genotype (P < 0.005) | 20/20 vs 20/− vs −/− | |||||||||||||
| Missmer et al. (61) | 1989-Jun 1994, Nurses' Health Study cohort | 418 control women, age mean NA | Cancer history | CA19: 63.3% (n = 622). Ethnicity all but eight women (cases + controls) Caucasian. HWE NA | Age, HRT use, menopausal status, time of/fasting status at blood draw | 173 vs 146 (P = 0.005) all women combined | 19/19 vs 19/− vs −/− | |||||||
| Stratified by fasting status, time of blood draw, HRT use | 183 vs 175 vs 155 (P = 0.10) premenopausal women | 19/19 vs −/− | ||||||||||||
| Values NA (P = 0.78) premenopausal women | 19/19 vs 19/− | |||||||||||||
| DeLellis et al. (66) | 1993-1996, Hawaii and Los Angeles, Multiethnic cohort | 230 postmenopausal women, age mean NA (range 45-75 y) | Cancer history, HRT use in previous 2 wk | CA19: African American 40.8%, Japanese American 39.0%, non-Latino White 69.1%, Latino White 64.0%. Genotypes 19/19 vs 19/− vs −/− differed “significantly” between ethnic groups. Ethnicity 65 African American, 50 Japanese American, 47 non-Latino White, 68 Latino White. HWE no evidence for departure (P = NA) | Crude and age-adjusted estimates presented | African American 150 (106-194) vs 166 (142-190) vs 150 (121-180; P ≥ 0.05) | 19/19 vs 19/− vs −/− | |||||||
| Japanese American 146 (101-190) vs 148 (130-167) vs 144 (119-169; P > 0.05) | 19/19 vs 19/− vs −/− | |||||||||||||
| Non-Latino White 146 (125-167) vs 142 (121-162) vs 160 (104-216; P > 0.05) | 19/19 vs 19/− vs −/− | |||||||||||||
| Latino White 118 (93-142) vs 126 (101-151) vs 149 (107-192; P > 0.05) | 19/19 vs 19/− vs −/− | |||||||||||||
| Kato et al. (57) | 1998-1999, Louisiana, Prostate screening program, breast clinic attendees, hospital employees | 60 men, age mean NA (range 48-86). 53 women, age mean NA (range 22-73) | Diabetes, cancer history, “any other serious condition” | CA19: Caucasians 30.4%, African Americans 18.4%. Frequency of 19 allele higher in Caucasian (P = 0.04). Ethnicity 56 Caucasian, 57 African American. HWE tested in all ethnic groups combined (P = 0.219) | Age, ethnicity matching to prostate/breast cancer cases: (a) hormone use, age, smoking, log height (African American women); (b) hormone use and age <40 (Caucasian women), (c) log-height, log body mass index (African American men) NA (Caucasian men) | African American women 110.8 vs 95.5 (P = 0.35) | 19/− vs −/− | |||||||
| Caucasian women 88.2 vs 92.3 (P = 0.79) | 19/− vs −/− | |||||||||||||
| African American men 106.9 vs 94.9 (P = 0.43) | 19/− vs −/− | |||||||||||||
| Caucasian men 94.8 vs 118.7 (P = 0.091) | 19/− vs −/− | |||||||||||||
| Rietveld et al. (60) | 1990-1993, Rotterdam, the Netherlands. Population-based cohort (myocardial infarction cases) | 80 men, 88 women, age mean 67.4 y | Age <55 or >75 y | CA19: 63.7% for random sample. Ethnicity Caucasian. HWE NA | Age group to myocardial infarction cases, gender, body mass index | 143.8 (134.8-152.8) vs 126.9 (117.9-135.9; P = 0.01). Combined figures for random sample (n = 168) and for those selected on genotype (n = 150) | 19/19 vs −/− | |||||||
| 150 selected on IGF-I genotype (59), age NA | Age <55 or >75 y, diabetes, HRT | |||||||||||||
| IGF-I (intronic STR) | ||||||||||||||
| Arends et al. (70) | Study period NA, location NA. Family-based association study comparing transmission of alleles | 124 children born small for gestational age and their parents, age mean NA | Neonatal complications, endocrine and metabolic disorders (children) | NA (not population-based). Ethnicity 113 Caucasians, 1 Asian, 1 Indo-Mediterranean, 4 mixed | Showed preferential transmission of 191-bp allele (P = 0.02) and lower IGF-I levels in children with this allele. −1.1 vs −0.5 SD scores (P = 0.03) | |||||||||
| IGF-II (A/G ApaI RFLP in 3′ untranslated region) | ||||||||||||||
| O'Dell et al. (73) | Study period NA, Northwick Park, United Kingdom. Northwick Park Heart cohort | 92 men (48 common, 44 rare homozygotes), age mean NA (range 45-65 y) | NA | A 0.28, G 0.72. Ethnicity Caucasian. HWE “applied” | 614.0 ± 124.0 vs 683.3 ± 146.9 (P = 0.01) | GG vs AA | ||||||||
| IGFBP-3 (A/C single nucleotide polymorphism at nucleotide −202) | ||||||||||||||
| Deal et al. (75) | 1982-1995, Physicians' Health Study (colorectal cancer cases) | 478 men (cases and controls), age mean NA (range 40-84 y) | History of cancer, myocardial infarction, stroke, transient ischemic attack, current liver/renal disease, peptic ulcer, gout, vitamin A use, β-carotene supplement at start of study | A 0.46, C 0.54. Ethnicity NA. HWE tested in cases and controls combined | R2 for polymorphism was 0.077 | 3,274 vs 2,753 (SD NA) for controls only | AA vs CC | |||||||
| 3180 vs 3000 vs 2760 in cases and controls combined (approximate figures from graphs, exact figures NA) | AA vs AC vs CC | |||||||||||||
| Jernström et al. (56) | Study period NA, Toronto, Canada. Healthy volunteers | 311 women, age 25.4 y (range 17-35) | Non-Caucasian, ever pregnant, cancer, diabetes, hysterectomy, estrogen non–oral contraceptive use | A 0.47, C 0.53. Ethnicity Caucasian. HWE NA | 4,390 vs 4,130 vs 3,840 | AA vs AC vs CC | ||||||||
| Schernhammer et al. (80) | 1989-Jun 1996, Nurses' Health Study cohort (breast cancer cases) | 943 women (cases and controls), age mean NA | Cancer history | A 0.46, C 0.54 in cases and controls combined. Ethnicity NA. HWE tested in cases and controls combined (P > 0.90) | Age, menopausal status, HRT use, blood draw details. R2 for polymorphism was 0.06 | 4,426 (4,291-4,561) vs 4,060 (3,970-4,150) vs 3,697 (3,581-3,813) in cases and controls combined (Plinear trend < 0.001) | AA vs AC vs CC | |||||||
NOTE: 19/19, homozygous for 19 allele; 19/−, heterozygous for 19 allele; −/−, no copies of 19 allele.
Where data are from case-control studies and where possible HWE Ps, allele frequencies and serum measurements for controls only are given unless stated otherwise.
Where serum levels were quoted as nmol/L, we converted to ng/mL by dividing by 0.13 (IGF-I) or 0.035 (IGFBP-3) (DSL product information, DSL-10-5600 and DSL-10-6600).
Crude effect estimates unless stated otherwise.
329 White women genotyped, but Table 2 of original article shows results for only 655 alleles.
Kim et al. (63) discuss a discrepancy between the IGF-I nucleotide sequence observed in their Korean women (absence of GA immediately 3′ to the CA microsatellite) compared with the IGF-I sequence in the National Center for Biotechnology Information database Genbank M12659 (presence of GA immediately 3′ to the CA microsatellite). These two (GA) nucleotides are not present in the IGF-I sequence on the human chromosome 12 contig or in the IGF-I nucleotide sequence of two Caucasian subjects (N. Johnson, personal communication.) and possibly reflect an error in the original M12659 sequence.