BACKGROUNDThere have been several epidemiologic studies investigating the association between circulating levels of insulin‐like growth factor I (IGF‐I), insulin‐like growth factor binding protein 3 (IGFBP‐3), and insulin in relation to the risk of prostate carcinoma, with conflicting results. To examine this issue further, the authors conducted a nested case–control study within the Cardiovascular Health Study cohort.METHODSIn men who were diagnosed with prostate carcinoma (cases) between 1990 and 1999 (n = 174), the levels of IGF‐I, IGFBP‐3, and insulin were measured on blood samples that were obtained 1–9 years prior to diagnosis (mean, 3.4 years). Similar measurements were made on 174 male participants without prostate carcinoma (controls) who were matched to cases based on the year blood was drawn, survival until the date of diagnosis, race, and age.RESULTSRelative to the men with IGF‐I levels in the first (lowest) quartile of the distribution, the risk of prostate carcinoma for men in the second, third, and fourth (upper) quartiles were 0.77 (95% confidence interval [95% CI], 0.43–1.38), 0.73 (95% CI, 0.41–1.30), and 0.67 (95% CI, 0.37–1.25), respectively. The results were influenced little by adjustment for levels of IGFBP‐3 or, instead, by evaluating the molar IGF‐I/IGFBP‐3 ratio. An analysis that was restricted to men who had plasma prostate‐specific antigen levels < 4 ng/mL at the time of the blood draw yielded similar results. The corresponding relative risks for IGFBP‐3 were 0.91 (95% CI, 0.49–1.68), 0.47 (95% CI, 0.25–0.94), and 0.65 (95% CI, 0.35–1.20), respectively. The distribution of serum insulin levels in cases and controls were nearly identical.CONCLUSIONSThe IGF‐I level was not associated positively with the risk of prostate carcinoma; however, an increase in the IGFBP‐3 level was associated with a modest decrease in risk. Cancer 2005. © 2004 American Cancer Society.
Increases in risk of breast cancer in successive generations of migrants to the United States from China and rapid temporal changes in incidence rates in China following social and economic changes clearly implicate environmental factors in the etiology of this disease. Case-control and cohort studies have provided evidence that at least some of these factors may be dietary. Iron, an essential element necessary for cell function, has also been demonstrated to have potential carcinogenic and co-carcinogenic activities. Iron overload, which was previously uncommon, has become more common in the United States than iron deficiency and may be increasing in China concurrently with dramatic increases in meat consumption. A case-control study nested in a cohort of women in Shanghai, China, was conducted to evaluate possible associations between risk of proliferative and nonproliferative fibrocystic changes as well as breast cancer and dietary iron intake and plasma ferritin levels. Plasma ferritin levels and reported dietary iron intake were compared in 346 women with fibrocystic changes, 248 breast cancer cases and 1,040 controls. Increasing ferritin levels were significantly associated with increasing risk of nonproliferative fibrocystic changes (OR: 2.51, 95% CI: 1.16-5.45, p trend 5 0.04). Similar, but weaker, trends were observed for proliferative changes and for breast cancer. Risk of breast cancer relative to the risk of fibrocystic changes was associated with dietary iron intake in women with nonproliferative fibrocystic changes (OR: 2.63, 95% CI: 1.04-6.68, p 5 0.02). In conclusion, this study finds significant associations between iron (stored and dietary) and fibrocystic disease and breast cancer. ' UICCKey words: breast cancer; iron; ferritin; fibrocystic breast disease; breast cancer risk factors Although mortality and incidence rates of breast cancer remain lower in China than in the United States, they have been increasing in recent decades.1,2 These increases in rates have been correlated with changes in the Chinese diet, including an increase in consumption of fat, fruits, eggs, meat, and the percent of energy derived from animal fats, indicating a move towards a more westernized diet.3-5 Similar dietary changes and temporal trends in breast cancer rates have been observed in Chinese migrants to the United States and other high-risk countries and in their descendents. [6][7][8]
Alcohol-related liver disease and hepatitis C were the most commonly identified etiologies among these American Indian patients with chronic liver disease in clinical care. Identifying American Indian and Alaska Native patients with chronic liver disease and providing treatment are critical for reducing disease burden.
We investigated whether circulating insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) levels are associated with the risk of fibrocystic breast conditions (FBC), in a case-control study nested within a randomized trial of breast self-examination conducted in Shanghai, China. Participants were enrolled during 1989-1991 and were followed over 10 years for the development of breast diseases. Controls (n 5 897) were frequency-matched by age to cases (n 5 451), who were diagnosed with FBC between 1995 and 2000. Circulating IGF-I and IGFBP-3 levels and their molar ratio were positively associated with risk of FBC. The odds ratios (ORs) and 95% confidence intervals (CI) for the upper fourth of the distribution compared to the lowest fourth for IGF-I, IGFBP3 and their molar ratio were 3.02 (2.02-4.52), 1.92 (1.37-2.71) and 2.26 (1.52-3.36), respectively. The strength of the association between IGF-I levels and FBC was attenuated after adjustment for IGFBP-3 and that for IGFBP-3 was largely eliminated after adjustment for IGF-I. Increasing levels of IGF-I were particularly associated with increasing risk of FBC with proliferative elements (ORs and 95% CIs for the 2nd, 3rd and upper fourth of the distribution of IGF-I: 3.13 (1.50-6.53), 4.57 (2.22-9.39) and 6.30 (3.08-12.89), compared with the lowest fourth. Our results suggest that elevated levels of IGF-I may contribute to the development of FBC. ' 2005 Wiley-Liss, Inc.Key words: insulin-like growth factor; insulin-like growth factor binding protein-3; breast cancer; fibrocystic breast conditions; Chinese Insulin-like growth factors (IGFs) are potent mitogenic and anti-apoptotic factors that regulate cell proliferation, differentiation and apoptosis. [1][2][3] The effect of IGFs is modulated by at least 6 high affinity IGF-binding proteins (IGFBPs); 4,5 greater than 95% of circulating IGF-I is complexed with IGFBP-3 and an acid-labile subunit. 6 The majority of IGF-I and IGFBPs are produced by the liver, the rest by a wide variety of tissues. 2 There are several reasons to suspect that the circulating levels of IGF-I and IGFBP-3 could influence breast cancer risk. In in vitro studies, IGF-I modulates gene expression and growth of the breast cancer cell line 8 Expression of IGF-I receptors affect responsiveness of MCF-7 cells to IGF-I and estradiol. 9 Evidence from breast cancer cell lines, experimental animal models and epidemiologic studies suggests that there is a synergistic effect between IGF-I and estrogens and androgens on cell proliferation and breast cancer risk. 10-14 Breast epithelial cells and stromal tissues have been shown to contain IGF-I and IGF-II proteins, [15][16][17][18]19 as well as IGFs mRNA 20,21 and IGF-I receptor. 22 In addition to modulation of IGF availability and action, IGFBPs have been shown to inhibit cellular growth [23][24][25][26] and IGF-I receptor activation, 27 and enhance apoptosis. 28,29 In a mouse mammary model, a reduced circulating IGF-I level delayed the onset of chemically and genet...
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