Kaaks R, Toniolo P, Akhmedkhanov A, Lukanova A, Biessy C, Dechaud H, Rinaldi S, Zeleniuch-Jacquotte A, Shore R E, Riboli E
International Agency for Research on Cancer, Lyon, France.
J Natl Cancer Inst. 2000 Oct 4;92(19):1592-600. doi: 10.1093/jnci/92.19.1592.
Leading a Western lifestyle, being overweight, and being sedentary are associated with an increased risk of colorectal cancer. Recent theories propose that the effects of these risk factors may be mediated by increases in circulating insulin levels and in the bioactivity of insulin-like growth factor (IGF)-I. To test this hypothesis, we conducted a case-control study nested within a cohort of 14 275 women in New York.
We used blood samples that had been obtained from these women from March 1985 through June 1991 and stored in a biorepository. C-peptide (a marker for insulin secretion), IGF-I, and IGF-binding proteins (IGFBPs)-1, -2, and -3 were assayed in the serum of 102 women who subsequently developed colorectal cancer and 200 matched control subjects. Logistic regression was used to relate cancer risk to these peptide levels, by adjustment for other risk factors. All statistical tests used are two-sided.
Colorectal cancer risk increased with increasing levels of C-peptide (P:(trend) =.001), up to an odds ratio (OR) of 2. 92 (95% confidence interval [CI] = 1.26-6.75) for the highest versus the lowest quintiles, after adjustment for smoking. For colon cancer alone (75 case subjects and 146 control subjects), ORs increased up to 3.96 (95% CI = 1.49-10.50; P:(trend) <.001) for the highest versus the lowest quintiles. A statistically significant decrease in colorectal cancer risk was observed for increasing levels of IGFBP-1 (P:(trend) =.02; OR in the upper quintile = 0.48 [95% CI = 0.23-1. 00]), as well as for the highest quintile of IGFBP-2 levels (P:(trend) =.06; OR = 0.38 [95% CI = 0.15-0.94]). Colorectal cancer risk showed a modest but statistically nonsignificant positive association with levels of IGF-I and was statistically significantly increased for the highest quintile of IGFBP-3 (OR = 2.46 [95% CI = 1. 09-5.57]).
Chronically high levels of circulating insulin and IGFs associated with a Western lifestyle may increase colorectal cancer risk, possibly by decreasing IGFBP-1 and increasing the bioactivity of IGF-I.
采用西方生活方式、超重和久坐不动与结直肠癌风险增加相关。最近的理论提出，这些风险因素的影响可能通过循环胰岛素水平及胰岛素样生长因子（IGF）-I生物活性的增加来介导。为验证这一假设，我们在纽约14275名女性队列中开展了一项巢式病例对照研究。
我们使用了1985年3月至1991年6月期间从这些女性身上采集并储存在生物样本库中的血样。对102名随后患结直肠癌的女性及200名匹配的对照者的血清进行C肽（胰岛素分泌标志物）、IGF-I以及IGF结合蛋白（IGFBP）-1、-2和-3的检测。通过对其他风险因素进行校正，采用逻辑回归分析将癌症风险与这些肽水平相关联。所有统计检验均为双侧检验。
校正吸烟因素后，结直肠癌风险随C肽水平升高而增加（P（趋势）=0.001），最高五分位数与最低五分位数相比，比值比（OR）为2.92（95%置信区间[CI]=1.26 - 6.75）。仅就结肠癌而言（75例病例和146例对照），最高五分位数与最低五分位数相比，OR高达3.96（95%CI = 1.49 - 10.50；P（趋势）<0.001）。观察到随着IGFBP-1水平升高，结直肠癌风险有统计学显著降低（P（趋势）=0.02；最高五分位数的OR = 0.48[95%CI = 0.23 - 1.00]），IGFBP-2水平最高五分位数时也是如此（P（趋势）=0.06；OR = 0.38[95%CI = 0.15 - 0.94]）。结直肠癌风险与IGF-I水平呈适度但无统计学显著意义的正相关，IGFBP-3最高五分位数时结直肠癌风险有统计学显著增加（OR = 2.46[95%CI = 1.09 - 5.57]）。
与西方生活方式相关的循环胰岛素和IGF长期高水平可能增加结直肠癌风险，可能是通过降低IGFBP-1和增加IGF-I的生物活性来实现。
