Weijenberg Matty P, Lüchtenborg Margreet, de Goeij Anton F P M, Brink Mirian, van Muijen Goos N P, de Bruïne Adriaan P, Goldbohm R Alexandra, van den Brandt Piet A
Department of Epidemiology, Nutrition and Toxicology Research Institute Maastricht, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands
Cancer Causes Control. 2007 Oct;18(8):865-79. doi: 10.1007/s10552-007-9032-6. Epub 2007 Jul 18.
To investigate baseline fat intake and the risk of colon and rectal tumors lacking MLH1 (mutL homolog 1, colon cancer, nonpolyposis type 2) repair gene expression and harboring mutations in the APC (adenomatous polyposis coli) tumor suppressor gene and in the KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) oncogene.
After 7.3 years of follow-up of the Netherlands Cohort Study (n = 120,852), adjusted incidence rate ratios (RR) and 95% confidence intervals (CI) were computed, based on 401 colon and 130 rectal cancer patients.
Total, saturated and monounsaturated fat were not associated with the risk of colon or rectal cancer, or different molecular subgroups. There was also no association between polyunsaturated fat and the risk of overall or subgroups of rectal cancer. Linoleic acid, the most abundant polyunsaturated fatty acid in the diet, was associated with increased risk of colon tumors with only a KRAS mutation and no additional truncating APC mutation or lack of MLH1 expression (RR = 1.41, 95% CI 1.18-1.69 for one standard deviation (i.e., 7.5 g/day) increase in intake, p-trend over the quartiles of intake <0.001). Linoleic acid intake was not associated with risk of colon tumors without any of the gene defects, or with tumors harboring aberrations in either MLH1 or APC.
Linoleic acid intake is associated with colon tumors with an aberrant KRAS gene, but an intact APC gene and MLH1 expression, suggesting a unique etiology of tumors with specific genetic aberrations.
研究基线脂肪摄入量与缺乏错配修复基因同源物1（MLH1，结肠癌，非息肉病2型）表达、腺瘤性息肉病基因（APC）肿瘤抑制基因突变及KRAS（ Kirsten大鼠肉瘤病毒癌基因同源物）癌基因突变的结肠和直肠肿瘤风险之间的关系。
在荷兰队列研究（n = 120,852）进行7.3年随访后，基于401例结肠癌患者和130例直肠癌患者计算调整后的发病率比（RR）和95%置信区间（CI）。
总脂肪、饱和脂肪和单不饱和脂肪与结肠癌或直肠癌风险以及不同分子亚组均无关联。多不饱和脂肪与直肠癌总体或亚组风险之间也无关联。饮食中最丰富的多不饱和脂肪酸亚油酸，与仅KRAS突变且无额外APC基因截短突变或MLH1表达缺失的结肠肿瘤风险增加相关（摄入量每增加一个标准差，即7.5克/天，RR = 1.41，95%CI 1.18 - 1.69，摄入量四分位数的p趋势<0.001）。亚油酸摄入量与无任何基因缺陷的结肠肿瘤风险或伴有MLH1或APC基因异常的肿瘤风险无关。
亚油酸摄入量与KRAS基因异常、APC基因完整且MLH1表达正常的结肠肿瘤相关，提示具有特定基因异常的肿瘤具有独特的病因。
