Diet and the prevention of cancer

Cancer ranks as the second-leading cause of death in developed countries and diet has long been suspected as playing a prominent role in its etiology. As a result, a substantial amount of research has been devoted to this field of study. Given the epidemiologic and biologic credibility, it is reasonable to attempt to identify specific nutrients, foods, or combination of these that are causally related to the development of cancer. Various study designs have been employed to generate and test specific hypotheses. In this review, we approach the dietary prevention of cancer primarily from an epidemiologic perspective. We examine the growing body of evidence on dietary etiologic factors and explore the practical prospects for prevention of cancer overall. An attempt is also made to explain inconsistencies in the findings and provide ideas for future research efforts in this field.     

Parity and other reproductive factors and risk of adenomatous polyps of the distal colorectum (United States)

Evidence for an effect of reproductive factors on colorectal carcinogenesis is inconsistent and little is known about their role in development of precursor adenomatous polyps. We evaluated the relation between reproductive factors and distal colorectal adenomas (n = 982) during14 years of follow up of 26,983 participants in the Nurses' Health Study(United States). The women were free of diagnosed cancer or polyps in 1980,underwent endoscopy 1980-94, and had reported on their parity, oral contraceptive (OC) use, and ages at menarche, first term-pregnancy, and menopause. We calculated relative risks (RR) and 95 percent confidence intervals (CI) using multiple logistic regression. Women with higher parity had an increased risk of adenomas of the distal colorectum (P trend = 0.004;6+ cf 0 parity: RR = 1.3, CI = 0.9-1.8) or distal colon (P trend = 0.002, RR= 1.7, CI = 1.2-2.6). This association was significantly stronger among women with a family history of colorectal cancer ( P interaction = 0.03); comparing6+ term-pregnancies with nulliparity, among those with a family history, the RR for distal colon adenoma was 3.2 (CI = 1.4-7.2), while among those without a family history, the RR was 1.3 (CI = 0.8-2.2). We observed no association for distal colorectal adenoma and age at menarche, age at first term-pregnancy, ever use of OCs, or menopausal status. Further work is needed to clarify the relation of parity with colon adenoma risk. This revised version was published online in July 2006 with corrections to the Cover Date.     

Determinants of tissue estradiol levels and biologic responsiveness in breast tumors

Estradiol stimulates the growth of breast tumor cells in both pre- and post menopausal women. Following the menopause, the levels of estradiol in breast tumor tissues are similar to those from tumors obtained prior to cessation of ovarian function, even though plasma estrogen levels are 10–50 fold lower in post- than in premenopausal women. These observations suggested the possibility of enhanced estradiol uptake from plasma or in situ synthesis in post-menopausal women. We systematically studied these possibilities in a series of model systems. Initially we demonstrated a very high affinity estradiol binding site in tissues from castrated rats. Enhanced uptake occurred under conditions of low plasma estrogen levels when compared to animals with higher estradiol levels. In situ synthesis also occurred both through the sulfatase and aromatase pathways. In further studies, we compared uptake from plasma with in situ synthesis via aromatase in a nude mouse model. Under the conditions utilized, in situ synthesis resulted in much higher tissue estradiol levels and tumor growth rates than did uptake from plasma. During these studies we demonstrated that tumors deprived of estradiol developed mechanisms rendering them more sensitive to estrogen. This involved the ability of cells to adapt to estradiol deprivation to allow them to be responsive to four log lower amounts of estrogen than when studied under wild type conditions. In addition, cells adapted by increasing their level of aromatase and thus developing the capability to become more sensitive to estrogen precursors. Taken together, these studies demonstrate that breast cancer tissue is highly plastic and can adapt to conditions of estrogen deprivation via a variety of mechanisms.     

Colonic Cell Proliferation in Normal Mucosa of Patients with Colon Cancer

Cell kinetics parameters have been analysed in colonic mucosa at different distances from a tumour in patients with colon carcinoma. Total cell number (TCN), H thymidine labelling index (TLI), mitotic index (MI), Goblet cell index (GCI) and the distribution of labelled cells along the crypt column (cell position frequency plot) were determined in well-aligned crypts. Total cell number, GCI and the labelled cell position frequency plots were similar in different samples from the same individual. A negative linear correlation between TCN and TLI was observed. The analysis of the cell position plots showed two patterns 1) with a high concentration in the bottom fifth of the crypt and 2) with frequent labelled cells at high positions. Whereas a negative correlation between overall TLI and the percent contribution to the TLI of the lowermost fifth was seen, the correlation was positive for the next 3 fifths and labelling was absent in the last part of the crypt.     

Preoperative low molecular weight heparin as venous thromboembolism prophylaxis in patients at risk for prosthetic infection after knee arthroplasty.

OBJECTIVE: To investigate the effect of preoperative initiation of low molecular weight heparin as prophylaxis for deep venous thrombosis in patients at risk of developing surgical-site infections after knee arthroplasty. DESIGN: Case-control study nested in a cohort. The incidence of surgical-site infection in the cohort was calculated. With the use of data extracted from medical histories and after adjustment for other risk factors, the effect of preoperative heparinization on the risk of incisional and prosthetic infection among case-patients and control-patients (1:3 ratio) was assessed. SETTING: Orthopedic department in a tertiary-care referral hospital. PATIENTS: A cohort of 160 consecutive patients who had received prosthetic knee implants between October 1, 2001, and November 30, 2003. RESULTS: Eighteen patients with surgical-site infections were identified, yielding an incidence of incisional and prosthetic infection of 6.9 (95% confidence interval [CI95], 3.5 to 12.0) and 4.4 (CI95, 1.8 to 8.8) cases per 100 patients undergoing surgery, respectively. Surgical-site infection was associated with preoperative use of low molecular weight heparin (odds ratio [OR], 6.2 after adjustment for medical and surgical factors; CI95 1.5 to 23). Prosthetic infection was strongly associated with preoperative use of prophylaxis (OR, undetermined [100% exposure in case-patients vs 35% exposure in control-patients]; P = .002), but incisional surgical-site infection was not. CONCLUSION: The use of low molecular weight heparins immediately before knee arthroplasty as prophylaxis for deep venous thrombosis should be questioned because of probable increased risk of prosthetic infection.