The MTHFR C677T polymorphism and colorectal cancer: the multiethnic cohort study.

Methylenetetrahydrofolate reductase (MTHFR) is a key regulatory enzyme in the metabolism of folate, a nutrient that has been inversely related to colorectal cancer risk. The common C677T variant in the MTHFR gene results in a reduced activity of this enzyme, thereby increasing the availability of folate for the production of thymidylate and purine for DNA synthesis and repair. We investigated the association of the 677TT genotype with colorectal cancer in a case-control study of 822 cases and 2,021 controls nested within the Multiethnic Cohort Study. The Multiethnic Cohort Study is a large prospective study of men and women of Japanese, White, African American, Latino, and Native Hawaiian origin, residing in Hawaii and Los Angeles. After adjusting for covariates, we found an inverse association between colorectal cancer risk and the TT genotype, with odds ratios (OR; and 95% confidence intervals) for the CC, CT, and TT genotypes of 1.00, 1.01 (0.84-1.21), and 0.77 (0.58-1.03), respectively. This association was similar in both sexes, stronger at high levels of folate intake, and limited to light and nondrinkers (P for interaction with ethanol = 0.02). An analysis by subsite (rectum versus colon) and stage (regional/distant versus in situ/localized) showed that the inverse association with the TT genotype was limited to colon tumors, especially those diagnosed at an advanced stage. The OR for the TT versus CC genotype for early- and late-stage colon cancer was 0.88 (0.58-1.33) and 0.52 (0.32-0.85), respectively (P for difference in OR = 0.04). The frequency of the T allele was relatively low in African Americans (0.13) and Native Hawaiians (0.22), consistent with their greater likelihood of presenting at a late stage when diagnosed with colorectal cancer. This study corroborates previous findings of an inverse association of the MTHFR 677TT genotype with colorectal cancer, especially at high levels of folate and low levels of ethanol intake. It also suggests that this effect may be specific to advanced colon cancer.     

Association of an exon 1 polymorphism in the IGFBP3 gene with circulating IGFBP-3 levels and colorectal cancer risk: the multiethnic cohort study.

Laboratory and seroepidemiologic studies have suggested that insulin-like growth factor binding protein-3 (IGFBP-3), the main binding protein for IGF-I, may be protective against colorectal cancer. We investigated the association of two polymorphisms (A-202C and G2133C) in the IGFBP3 gene with plasma IGF hormone levels among 887 randomly selected participants in the Multiethnic Cohort study. We found that these two genetic variants were in strong linkage disequilibrium and were both inversely associated with plasma IGFBP-3. However, the effect on plasma IGFBP-3 levels was stronger for the G2133C variant than the A-202C variant. Thus, we assessed the colorectal cancer risk associated with the G2133C in a case-control study of 817 cases and 1,995 controls nested within the Multiethnic Cohort study. Under the assumption of dominant genetic model, carriers of the 1233C allele were at 32% increased risk of colorectal cancer [95 % confidence interval (95% CI) for the odds ratio (OR), 1.07-1.62] and that this effect seemed stronger for the rectum (OR for the C allele, 1.95; 95% CI, 1.35-2.83) than the colon (OR, 1.16; 95% CI, 0.92-1.45). These data suggest that the exon 1 G2133C missense variant in IGFBP3 may be a susceptibility factor for colorectal cancer.     

Case-control study of diet and other risk factors for gastric cancer in Hawaii (United States)

Objective: To investigate the association of diet and other factors with gastric adenocarcinoma of the distal stomach. Methods: Three hundred cases and 446 population-based controls were interviewed with a quantitative, food frequency questionnaire, which listed over 250 foods. The questionnaire also included information on smoking history, alcohol intake, education, medical history, medication use, and a family history of cancer. Results: Cigarette smoking, family history of gastric cancer and personal history of gastric ulcer were positively associated with gastric cancer, while education and past use of non-steroidal anti-inflammatory drugs were inversely related to risk. The consumption of all vegetables, mainly dark green, light green, and yellow vegetables, reduced risk. Many of these vegetables contain -carotene, vitamin C, vitamin E or folate, which were also inversely related to gastric cancer risk. When these nutrients were analyzed simultaneously, the inverse association was mainly with -carotene. The intake of processed meats and bacon was positively associated with gastric cancer risk, but primarily in men. When we simultaneously adjusted these meats for the intake of the different vegetables, the association was no longer significant. Conclusions: These findings provide additional support that the consumption of dark green and yellow vegetables are protective against adenocarcinoma of the distal stomach.     

The relationship between twenty missense ATM variants and breast cancer risk: the Multiethnic Cohort.

Deficiencies in tasks of detecting and repairing DNA damage lead to mutations and chromosomal abnormalities, a hallmark of cancer. The gene mutated in ataxia-telangiectasia (A-T), ATM, is a proximal component in performing such tasks. Studies of A-T families have suggested an increased risk of breast cancer among obligate female heterozygous carriers of ATM mutations. Paradoxically, studies of sporadic and familial breast cancer have failed to demonstrate an elevated prevalence of mutations among breast cancer cases. We characterized the prevalence and distribution of 20 ATM missense mutations/polymorphisms in a population-based case-control study of 854 African-American, Latina, Japanese, and Caucasian women aged >/==" BORDER="0">45 years participating in the Multiethnic Cohort Study. The study population included 428 incident breast cancer cases and 426 controls. The prevalence of variants ranged from 0% to 13.6% among controls and varied by ethnicity (0-32.5%). Overall, these data provide little support for an association of ATM missense mutations with breast cancer among older women. We observed only one sequence variation (L546V), common among African-American women, to be overrepresented among all high-stage breast cancer cases (odds ratio, 3.35; 95% confidence interval, 1.27-8.84). After correction for multiple comparisons, this observed risk modification did not attain statistical significance. The distribution of ATM missense mutations and polymorphisms varied widely across the four ethnic groups studied. Although a single missense variant (L546V) appeared to act as a modest predictor of risk, the remaining variants were no more common in breast cancer cases as compared with controls.     

A pooled analysis of case–control studies of thyroid cancer. IV. Benign thyroid diseases

Objective: To obtain more precise estimates of the association between thyroid cancer and benign thyroid diseases and to elucidate the role of potential confounders or effect modifiers.Methods: The original data from 12 case–control studies from the United States, Asia, and Europe were pooled. Based on 2094 women and 425 men with cancer of the thyroid and, respectively, 3248 and 928 control subjects, odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were obtained by conditional regression models, conditioning on study and age at diagnosis, and adjusting for age and radiotherapy.Results: A history of hypothyroidism was not associated with cancer risk (pooled ORs=0.9, 95% confidence interval, CI: 0.7–1.3 in women and 1.7, 95% CI: 0.3–11.7 in men). ORs for hyperthyroidism were 1.4 (95% CI: 1.0–2.1) in women and 3.1 (95% CI: 1.0–9.8) in men. In women, however, risk was lower in the absence of or after allowance for history of goiter. Pooled ORs for a history of goiter were 5.9 (95% CI: 4.2–8.1) in women and 38.3 (95% CI: 5.0–291.2) in men. Risk for a history of benign nodules/adenomas was especially high (OR=29.9, 95% CI: 14.5–62.0, in women; 18 cases versus 0 controls in men). The excess risk for goiter and benign nodules/adenomas was greatest within 2–4 years prior to thyroid cancer diagnosis, but an elevated OR was present 10 years or more before cancer.Conclusions: Goiter and benign nodules/adenomas are the strongest risk factors for thyroid cancer, apart from radiation in childhood.     

迷迭香酸抗血栓和抗血小板聚集作用

迷迭香酸是丹参水溶性成分之一。大鼠体内实验(iv)表明,它能抑制静脉血栓形成。阻抑胶原诱导的血小板聚集,促进纤维蛋白溶解活性。当剂量为50及100 mg/kg时,血栓形成的抑制率分别为41.9和54.8%(P<0.vv05)。当剂量为100及150mg/kg时,血小板聚集的抑制率分别为30.4%(P<0.05)和46.4%(P<0.01),血浆优球蛋白溶解时间缩短(P<0.05)。纤维蛋白原含量无明显变化。以上结果说明,迷迭香酸有温和的抗血栓作用。其机理可能与抗血小板聚集和增强纤维蛋白溶解活性有关。