Estimating the global and regional burden of suboptimal nutrition on chronic disease: methods and inputs to the analysis.

BACKGROUND/OBJECTIVES: Global burdens of cardiovascular disease (CVD), diabetes and cancer are on the rise. Little quantitative data are available on the global impact of diet on these conditions. The objective of this study was to develop systematic and comparable methods to quantitatively assess the impact of suboptimal dietary habits on CVD, diabetes and cancer burdens globally and in 21 world regions. SUBJECTS/METHODS: Using a comparative risk assessment framework, we developed methods to establish for selected dietary risk factors the effect sizes of probable or convincing causal diet-disease relationships, the alternative minimum-risk exposure distributions and the exposure distributions. These inputs, together with disease-specific mortality rates, allow computation of the numbers of events attributable to each dietary factor. RESULTS: Using World Health Organization and similar evidence criteria for convincing/probable causal effects, we identified 14 potential diet-disease relationships. Effect sizes and ranges of uncertainty will be derived from systematic reviews and meta-analyses of trials or high-quality observational studies. Alternative minimum-risk distributions were identified based on amounts corresponding to the lowest disease rates in populations. Optimal and alternative definitions for each exposure were established based on the data used to quantify harmful or protective effects. We developed methods for identifying and obtaining data from nationally representative surveys. A ranking scale was developed to assess survey quality and validity of dietary assessment methods. Multi-level hierarchical models will be developed to impute missing data. CONCLUSIONS: These new methods will allow, for the first time, assessment of the global impact of specific dietary factors on chronic disease mortality. Such global assessment is not only possible but is also imperative for priority setting and policy making.

Does intentional weight loss reduce cancer risk?

Epidemiologic evidence points to obesity as a major risk factor for many cancers, including cancers of the breast, endometrium, colorectum, kidney, oesophagus and pancreas. Whether intentional weight loss might reduce this excess risk is not yet proven. We searched the medical literature for studies reporting changes in cancer risk following intentional weight loss, and for studies reporting changes in cancer-relevant risk factors of oestrogens, sex hormone binding globulin (SHBG), Insulin-like growth factor-I (IGF-I), IGF binding proteins and selected inflammatory markers [C-reactive protein (CRP), interleukin 6 (IL-6) and tumour necrosis factor-α (TNF-α)]. Observational cohort studies and randomized controlled trials of both dietary interventions and bariatric surgery all indicate fairly immediate reductions in cancer incidence following intentional weight loss. Oestrogen levels drop and SHBG levels increase coincident with intentional weight loss, with about a one-third reduction in free oestradiol to be expected from a 10% weight loss. CRP levels also drop substantially after weight loss at about this same 3 : 1 ratio. Reductions in TNF-α and IL-6 are consistently seen, but of a smaller magnitude, and IGF-I and IGFBP changes after weight loss are small and inconsistent. Because both cancer incidence and levels of circulating cancer biomarkers drop fairly rapidly following weight loss, intentional weight loss may well lead to meaningful reductions in cancer risk with a short latency time.

Genetic variation in IGF1, IGFBP3, IRS1, IRS2 and risk of breast cancer in women living in Southwestern United States.

BACKGROUND: An insulin-related pathway to breast cancer has been hypothesized. METHODS: We examine the 19 CA repeat of the IGF1 gene, the -202 C > A IGFBP3, the G972R IRS, and the G1057D IRS2 polymorphisms among 1,175 non-Hispanic white (NHW) and 576 Hispanic newly diagnosed breast cancer cases and 1,330 NHW and 727 Hispanic controls living in Arizona, Colorado, New Mexico, and Utah. RESULTS: Among post-menopausal women not recently exposed to hormones, not having the 19 CA repeat of IGF1 gene was associated with breast cancer among NHW women [odds ratio (OR) 2.14, 95% confidence interval (CI) 1.21-3.79] and having an R allele of G972R IRS1 increased breast cancer risk among Hispanic women (OR 2.70, 95% CI 1.13-6.46). Among post-menopausal Hispanic women recently exposed to hormones the A allele of the -202 C > A IGFBP3 polymorphism increased risk of breast cancer (OR 1.57, 95% CI 1.06-2.33). The IGF1 19 CA repeat polymorphism interacted with hormone replacement therapy (HRT) among NHW post-menopausal women; women who had the 19/19 IGF1 genotype were at reduced risk of breast cancer (OR 0.64, 95% CI 0.47-0.88) if they did not use HRT. We also observed interaction between body mass index and IGF1 19 CA repeat (p=0.06) and between weight gain and the -202 C > A IGFBP3 polymorphism (p=0.05) in NHW post-menopausal women not recently exposed to hormones. CONCLUSIONS: Our data suggest that associations between insulin-related genes and breast cancer risk among women living in the Southwestern United States may be dependent on estrogen exposure and may differ by ethnicity.

The ID effect on youth access to cigarettes.

OBJECTIVE: To estimate the effect on cigarette sales rates when minors present identification (ID). DESIGN: Controlled experiment in which minors attempting to purchase cigarettes either carried a valid photo ID (documenting they were minors) or carried no ID, and were instructed to show the ID or admit having no ID if the clerk requested proof of age. SETTING: Census of retail stores in six urban and suburban Colorado counties. SUBJECTS: Retail cigarette clerks, uninformed of the study. MAIN OUTCOME MEASURES: Relative risk (RR) of cigarette sale to a minor when ID was requested and presented versus requested but not presented. RESULTS: When clerks requested ID, sales were more than six times as frequent if minors presented ID than if they did not (12.2% v 2.0%, RR 6.2, p < 0.0001). The relative risk remained substantially unchanged under adjustment for demographic and circumstantial covariates. CONCLUSIONS: Presentation of photo ID in compliance checks increases illegal cigarette sales to minors. The impact may vary among states or locales and depends strongly on how often clerks request proof of age. Clerk training and responsible cigarette sales practices should include age calculations from photo ID. Programmes relying on investigative purchase attempts to estimate actual rates of cigarette sales to minors should ascertain and replicate local ID presenting behaviours that minors typically use during genuine attempts to buy cigarettes.

18S ribosomal DNA typing and tracking of Acanthamoeba species isolates from corneal scrape specimens, contact lenses, lens cases, and home water supplies of Acanthamoeba keratitis patients in Hong Kong.

We examined partial 18S ribosomal DNA (Rns) sequences of Acanthamoeba isolates cultured in a study of microbial keratitis in Hong Kong. Sequence differences were sufficient to distinguish closely related strains and were used to examine links between strains obtained from corneal scrape specimens, contact lenses, lens cases, lens case solutions, and home water-supply faucets of patients with Acanthamoeba. We also looked for evidence of mixed infections. Identification of Acanthamoeba Rns genotypes was based on sequences of approximately 113 bp within the genus-specific amplicon ASA.S1. This permitted genotype identification by using nonaxenic cultures. Of 13 specimens obtained from corneal scrapes, contact lenses, lens cases, or lens case solutions, 12 were Rns genotype T4 and the remaining one was Rns genotype T3. The sequences of corneal scrape specimens of two patients also were the same as those obtained from their contact lenses or lens case specimens. A possible triple-strain infection was indicated by three different T4 sequences in cultures from one patient's lenses. Although faucet water used by patients to clean their lenses is a possible source of infections, specimens isolated from the faucets at two Acanthamoeba keratitis patients' homes differed from their corneal scrape or lens specimens. The overall results demonstrate the potential of this Rns region for tracking Acanthamoeba keratitis strains in infections and for distinguishing single-strain and closely related multiple-strain infections even when other microorganisms might be present with the cultured specimens. They also confirm the predominance of Rns genotype T4 strains in Acanthamoeba keratitis infections.

American Cancer Society guidelines for the early detection of cancer: update of early detection guidelines for prostate, colorectal, and endometrial cancers. Also: update 2001--testing for early lung cancer detection.

Updates to the American Cancer Society (ACS) guidelines regarding screening for the early detection of prostate, colorectal, and endometrial cancers, based on the recommendations of recent ACS workshops, are presented. Additionally, the authors review the "cancer-related check-up," clinical encounters that provide case-finding and health counseling opportunities. Finally, the ACS is issuing an updated narrative related to testing for early lung cancer detection for clinicians and individuals at high risk of lung cancer in light of emerging data on new imaging technologies. Although it is likely that current screening protocols will be supplanted in the future by newer, more effective technologies, the establishment of an organized and systematic approach to early cancer detection would lead to greater utilization of existing technology and greater progress in cancer control.

Nutrition during and after cancer treatment: a guide for informed choices by cancer survivors.

Many studies have been conducted about dietary interventions aimed at preventing cancer. The American Cancer Society has published guidelines on diet, nutrition and cancer prevention, which are updated periodically as new evidence emerges, and other groups, too, have issued statements or guidelines about nutritional strategies to prevent cancer. Much less is known, however, about optimal nutrition for cancer survivors. This report looks at the different phases of cancer survivorship, from active treatment to advanced disease, and presents existing evidence from which informed decisions can be made regarding dietary choices. Popular complementary and alternative methods related to dietary intervention are reviewed. Nutrition information is also provided according to common cancer sites. As this is an area that requires survivors and health care providers to communicate effectively, a special section on "frequently asked questions" is provided for use as a patient education handout.

Ki-ras proto-oncogene mutations in sporadic colorectal adenomas: relationship to histologic and clinical characteristics.

BACKGROUND & AIMS: [corrected] The goal of this study was to examine the relationship between Ki-ras mutations in colorectal adenomas and characteristics of both the subject (age, gender, and family/personal history of colonic neoplasia) and the adenoma (multiplicity, size, location, and histologic features). METHODS: Ki-ras mutations were detected by direct sequencing in 738 adenomatous polyps removed at baseline from 639 participants in a nutritional trial of adenoma recurrence. RESULTS: Ki-ras mutations were detected in 17.2% of the adenomas. Ki-ras mutations were unrelated to gender, family, or personal history of colonic neoplasia, location within the colorectum, or adenoma multiplicity, but were more common in older subjects (P = 0.01 for trend), in larger adenomas (P < 0.0001 for trend), in adenomas with villous histology (odds ratio [OR], 3.2; 95% confidence interval [CI], 2.1-4.9 vs. tubular), and in adenomas with high-grade dysplasia (32.0% vs. 13.6%; OR, 3.0; 95% CI, 1.9-4.6 vs. low-grade dysplasia). Multivariate analysis showed Ki-ras mutations to be independently associated with subject age (P = 0.01 for trend), tubulovillous/villous histology (OR, 2.3; 95% CI, 1.5-3.7), and high-grade dysplasia (OR, 1.9; 95% CI, 1.2-3.1). Adenoma size was not independently related to Ki-ras mutation. CONCLUSIONS: Ki-ras mutations are associated with the histologic features of adenoma progression (villous histology and high-grade dysplasia) rather than with adenoma growth.

Use of subgenic 18S ribosomal DNA PCR and sequencing for genus and genotype identification of acanthamoebae from humans with keratitis and from sewage sludge.

This study identified subgenic PCR amplimers from 18S rDNA that were (i) highly specific for the genus Acanthamoeba, (ii) obtainable from all known genotypes, and (iii) useful for identification of individual genotypes. A 423- to 551-bp Acanthamoeba-specific amplimer ASA.S1 obtained with primers JDP1 and JDP2 was the most reliable for purposes i and ii. A variable region within this amplimer also identified genotype clusters, but purpose iii was best achieved with sequencing of the genotype-specific amplimer GTSA.B1. Because this amplimer could be obtained from any eukaryote, axenic Acanthamoeba cultures were required for its study. GTSA.B1, produced with primers CRN5 and 1137, extended between reference bp 1 and 1475. Genotypic identification relied on three segments: bp 178 to 355, 705 to 926, and 1175 to 1379. ASA.S1 was obtained from single amoeba, from cultures of all known 18S rDNA genotypes, and from corneal scrapings of Scottish patients with suspected Acanthamoeba keratitis (AK). The AK PCR findings were consistent with culture results for 11 of 15 culture-positive specimens and detected Acanthamoeba in one of nine culture-negative specimens. ASA.S1 sequences were examined for 6 of the 11 culture-positive isolates and were most closely associated with genotypic cluster T3-T4-T11. A similar distance analysis using GTSA.B1 sequences identified nine South African AK-associated isolates as genotype T4 and three isolates from sewage sludge as genotype T5. Our results demonstrate the usefulness of 18S ribosomal DNA PCR amplimers ASA.S1 and GTSA.B1 for Acanthamoeba-specific detection and reliable genotyping, respectively, and provide further evidence that T4 is the predominant genotype in AK.

Surgical treatment of an intrastromal epithelial corneal cyst.

PURPOSE: To describe corneal intrastromal epithelial cysts and present a minimally invasive surgical technique successfully used to treat such a lesion. METHODS: A 5-year-old girl with a progressive, vision-threatening, intrastromal corneal opacity in the left eye is described. The patient had a history of accommodative esotropia and bilateral medial rectus recession two years before presentation. A presumptive diagnosis of an epithelial cyst secondary to iatrogenic seeding of the limbal corneal stroma was made. Because of documented growth toward the visual axis and a decrease in best-corrected visual acuity, surgical treatment was initiated. The cyst was incised and debrided through a 2.0-mm, partial-thickness, limbus-parallel, clear corneal incision. RESULTS: Cytologic analysis of the cyst contents showed intact and degenerated epithelial cells, thereby confirming the diagnosis. The cyst walls were scraped through the nonenlarged incision, and irrigation resulted in nearly complete clearing of the opacity. Stable vision and no recurrences were documented with 21 months of follow-up. CONCLUSION: This minimally invasive surgical approach may be a good alternative to previously described treatments for intrastromal corneal cysts.

Smoking during pregnancy and breast cancer risk in very young women (United States).

OBJECTIVE: To evaluate the association of smoking during a woman's first pregnancy, a period of pronounced growth and differentiation of mammary tissue, and her subsequent breast cancer risk. METHODS: In this matched case-control study, we used linked birth certificate and tumor registry data from the New York State Health Department. Cases were 319 women aged 26-45 who were diagnosed with breast cancer in New York State between 1989 and 1995 and who completed a first pregnancy in New York State after 1987 at least one year prior to diagnosis of cancer. Controls were 768 primiparous women matched to cases on county of residence and delivery date. Information on prenatal smoking and other factors characterizing the woman's first pregnancy was obtained from the pregnancy record of each subject, and the association of these factors to breast cancer risk was assessed using conditional logistic regression. RESULTS: Smoking during pregnancy was associated with increased risk for breast cancer (crude OR = 2.7, 95% confidence interval (CI): 1.1-6.3). Adjustment for maternal age, subject age, race, and education strengthened this association (OR = 4.8, CI 1.6-14.6). CONCLUSIONS: These findings suggest that cigarette smoking during a woman's first pregnancy may increase her risk for early-onset breast cancer.

Reducing risk for cardiovascular disease in uninsured women: combined results from two WISEWOMAN projects.

OBJECTIVE: to evaluate the effectiveness of a cardiovascular disease (CVD) risk factor reduction program for financially disadvantaged women. The program included cholesterol and blood pressure assessments and tailored physical activity and nutrition interventions. METHODS: Women who attended selected National Breast and Cervical Cancer Early Detection Program sites in North Carolina and Massachusetts received either enhanced physical activity and nutrition interventions (EI) or minimum interventions (MI). The effectiveness of EI was assessed by pooling data from the North Carolina and Massachusetts projects after 1 year, and a mixed models analysis of covariance was used to compare changes in CVD risk factors across groups. RESULTS: The blood pressure, total cholesterol, and high-density lipoprotein cholesterol profiles of both groups improved, body weight was maintained, and smoking declined. The 10-year estimated coronary heart disease death rate (per 1,000 women) at baseline was 64.8 for the El group and 61.9 for the MI group. The rate declined by 3.5 deaths per 1,000 for the EI and 0.7 per 1,000 for the MI. Although the decline was statistically significant for the EI group, the difference between groups was not significant. CONCLUSION: Further lifestyle intervention research targeting financially disadvantaged women is needed.

Birth characteristics and subsequent risk for breast cancer in very young women.

There is growing evidence that prenatal exposures may influence later breast cancer risk. This matched case-control study used linked New York State birth and tumor registry data to examine the association between birth characteristics and breast cancer risk among women aged 14-37 years. Cases were women diagnosed with breast cancer between 1978 and 1995 who were also born in New York after 1957 (n = 484). For each case, selected controls were the next six liveborn females with the same maternal county of residence. The authors found a J-shaped association between birth weight and breast cancer risk, and very high birth weight (> or =4,500 g) was associated with the greatest elevation in risk (adjusted odds ratio (OR) = 3.10, 95% confidence interval (CI): 1.18, 7.97). The association of maternal age with breast cancer risk was also J-shaped, with maternal age of more than 24 years showing a positive, linear association (adjusted OR = 1.94, 95% CI: 1.18, 3.18 for maternal age > or =35 vs. 20-24 years; p for trend = 0.02). In contrast, women born very preterm had a lower risk (adjusted OR = 0.11, 95% CI: 0.02, 0.79 for gestational age <33 vs. > or =37 weeks). These findings support a role for early life factors in the development of breast cancer in very young women.

Intentional weight loss and mortality among overweight individuals with diabetes.

OBJECTIVE: To estimate the effect of intentional weight loss on mortality in overweight individuals with diabetes. RESEARCH DESIGN AND METHODS: We performed a prospective analysis with a 12-year mortality follow-up (1959-1972) of 4,970 overweight individuals with diabetes, 40-64 years of age, who were enrolled in the American Cancer Society's Cancer Prevention Study I. Rate ratios (RRs) were calculated, comparing overall death rates, and death from cardiovascular disease (CVD) or diabetes in individuals with and without reported intentional weight loss. RESULTS: Intentional weight loss was reported by 34% of the cohort. After adjustment for initial BMI, sociodemographic factors, health status, and physical activity, intentional weight loss was associated with a 25% reduction in total mortality (RR = 0.75; 95% CI 0.67-0.84), and a 28% reduction in CVD and diabetes mortality (RR = 0.72; 0.63-0.82). Intentional weight loss of 20-29 lb was associated with the largest reductions in mortality (approximately 33%). Weight loss >70 lb was associated with small increases in mortality CONCLUSIONS: Intentional weight loss was associated with substantial reductions in mortality in this observational study of overweight individuals with diabetes.