Polygon method: A systematic margin assessment for breast conservation.

BACKGROUND: Radiation therapy (RT) for women with ductal carcinoma in situ (DCIS) undergoing breast-conserving surgery (BCS) may be overtreatment for some, especially for those in which DCIS is eradicated, and ipsilateral breast tumor recurrence (IBTR) risk approaches the contralateral breast cancer (CBC) level. The aim of this study was to clarify whether the polygon method, a new systematic method of en face (tangential, shaved) margin assessment, can identify a subset of DCIS that can be safely treated by BCS alone. METHODS: A key tool of the polygon method is an adjustable mold that prevents the "pancake phenomenon" (flattening) of breast tissue after surgical removal so that the specimen is fixed in the shape of a polygonal prism. This preanalytical procedure enables us to command a panoramic view of entire en face margins 3-5-mm deep from the real peripheral cut surfaces. Competing risk analysis was used to quantify rates of IBTR and CBC and to evaluate risk factors. RESULTS: From 2000 to 2013, we identified 146 DCIS patients undergoing BCS with a contralateral breast at risk. In 100 DCIS patients whose margin was negative by the polygon method, 5 IBTR (3 DCIS and 2 invasive ductal carcinoma [IDC]) and 10 CBC (6 DCIS and 4 IDC) cases were identified during a median follow-up of 7.6 years (range, 0.9-17.4). Five- and 10-year cumulative incidence rates were 3.0% and 5.3% for IBTR, and 7.1% and 13.3% for CBC, respectively. Thus, patients with a negative margin consistently showed at least twofold lower IBTR than CBC despite omission of RT. CONCLUSIONS: Japanese women classified with a negative margin by the polygon method show a very low risk of IBTR and account for approximately half of CBC cases. In this subset of DCIS patients, additional RT is not beneficial.

Dietary factors and the risk of gastric cancer among Japanese women: a comparison between the differentiated and non-differentiated subtypes.

PURPOSE: Using data from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC), a case-referent study was performed to clarify whether dietary habits differentially impact on the risk of female gastric cancers of different histological subtypes. METHODS: The study subjects comprised 508 histologically confirmed female gastric cancer cases (156 differentiated, 352 non-differentiated), identified via hospital cancer registry and surgical records between 1988 to 1998. The referents were 36,490 cancer-free first-visit female outpatients over 30 years old presenting at the center within the same period of time. The odds ratios were estimated by logistic regression analyses and adjusted for potential confounding factors. RESULTS: Frequent vegetable and fruit conferred reduced risk of both differentiated and non-differentiated female gastric cancers in similar patterns. In addition, reduced risk was observed for intake of fish and soybean products, particularly for the non-differentiated type. CONCLUSIONS: These results suggest that both differentiated and non-differentiated female gastric cancers are preventable by frequent intake of vegetable and fruit, fish and soybean products, suggested to be common protective factors, although the possibility of some variation in the impact of the diet on different histopathological entities needs to be further addressed.

Impact of established risk factors for breast cancer in nulligravid Japanese women.

BACKGROUND: The mechanism by which pregnancy impacts breast cancer risk remains poorly understood. There is a need for detailed quantification of risk in nulliparous women. We therefore have undertaken a case-referent study of breast cancer employing data from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC), Japan, examining the impact of reproductive and anthropometric factors on breast cancer risk among nulligravid women compared with their parous counterparts. METHODS: In total, 2032 breast cancer cases were included, and 17848 women, confirmed as free of cancer, were recruited as a reference group. Odds ratios (OR) and 95% confidence intervals (95% CI) were determined by multiple logistic regression analysis. RESULTS: A protective effect of later age at menarche was observed among parous women, but it did not alter risk in nulligravid cases. The risk increment with a family history appeared to be most pronounced among premenopausal cases with no history of pregnancy (OR=2.68, 95% CI: 1.41-5.11). Among postmenopausal women, positive associations with height and current body mass index (BMI) in the nulligravid group were similar to those observed in the parous group. The present study indicated that age at menopause, family history in premenopausal women, and height and obesity in postmenopausal women seemed to exert more influence in nulligravid women. Formal tests for interaction between maternity status and these factors, however, did not prove statistically significant. CONCLUSION: Our findings suggest that established risk factors for breast cancer have an additive impact with nulligravid status. Thus, it is implied that obesity control for all women, including nulliparous individuals, is important from a practical viewpoint for primary breast cancer prevention.

Height, weight, menstrual and reproductive factors and risk of gastric cancer among Japanese postmenopausal women: analysis by subsite and histologic subtype.

To clarify whether reproductive factors have an impact on gastric cancer in Japanese females, a case-control study was conducted using data from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC), Japan. The study subjects included 365 postmenopausal women with gastric cancer and 1,825 age-class frequency-matched noncancer outpatients presenting at Aichi Cancer Center in 1988-1998. Cases were further divided with regard to the anatomic subsite (upper third, middle third, lower third) and histologic subtypes (differentiated, nondifferentiated) and the association was evaluated using odds ratios (ORs) estimated by the logistic regression model, adjusting for potential confounding factors. A high body weight and corresponding body mass index at age 20 moderately increased the risk of gastric cancer, especially for middle third and nondifferentiated cancers. Risk fluctuation with early or late age at menarche and menopause and total duration of fertility was not consistent. Individuals with a high age at first parity tended to show decreased risk of cancer, irrespective of their subsite or histologic subtype. The ORs were decreased with a short average period of breastfeeding, especially for upper third and nondifferentiated cancers. From these results, however, it appears that height, weight, menstrual and reproductive factors have less impact on gastric cancer than environmental factors such as smoking and dietary habits or family history of gastric cancer.

Correlation between Food Consumption and Colorectal Cancer: An Ecological Analysis in Japan.

Objectives: Incidence rates for colorectal cancer are universally high in western countries while values in the orient are very variable. Japan is one of the oriental countries with a high incidence but any association with food components remains to be clarified. To explore specific nutrient effects on risk of colorectal cancer in Japan, we here conducted a correlation analysis between change in the diet and incidence rates. Methods: Incidence data for 1976-1996 and national values for per capita daily food nutrient intake in 1956-1995 were used. We first analyzed chronological changes of food nutrients and colorectal cancer, and then calculated correlation coefficients with time lags of 5, 10, 15 or 20 years. To adjust for the confounding effects of total energy, we also performed a partial correlation analysis. Results: Incidences of colorectal cancer gradually increased during 1976-1996 with the highest incidence rates for colon and rectal cancers, 25.31 and 13.75 per 100,000, respectively, in 1996. Food nutrient intake also demonstrated major variation during 1956-1995, total fats and oils increasing most, followed by animal protein and animal fats. Incidences of colorectal cancer were positively associated with fat and oil intake, of both plant and animal types; a positive link was noted with animal protein but the association with plant protein consumption was inverse, as was also the case for carbohydrate and cereals; no simple association was evident with total energy intake. Conclusions: Food nutrients play roles in risk of colon and rectal cancers. Lower animal protein and fat intake, and higher carbohydrate and cereal consumption might reduce the risk of colon and rectal cancers.

Valid Responses to ABO Blood Type Question in Self-reporting Questionnaire.

This paper reports the sensitivity and specificity of self-reported ABO blood type. Subjects were 283 outpatients who participated in Helicobacter pylori eradication program at Aichi Cancer Center Hospital. Excluding seven patients, an ABO blood test was successfully conducted for 276 participants (133 males and 143 females). Only three participants answered their blood type differently from the results of the blood test; one A-type male answered to be with AB type, one B-type male with AB type, and one AB-type male with A type. Nine participants stated that they did not know their ABO blood type. The sensitivity was 98.7% (95% confidence interval, 92.8-100.0%) for 75 O-type individuals, 96.1% (90.3-98.9%) for 102 A-type individuals, 92.9% (84.1-97.6%) for 70 B-type individuals, and 93.1% (77.2-99.2%) for 29 AB-type individuals, when the nine individuals were included. The specificity was more than 99% for any blood type. These findings revealed that self-reported ABO blood type is highly valid for epidemiologic studies.

Gene-environment Interactions and Polymorphism Studies of Cancer Risk in the Hospital-based Epidemiologic Research Program at Aichi Cancer Center II (HERPACC-II).

Genetic polymorphisms may modify the effects of environmental risk factors on cancer occurrence. We have recently launched a comprehensive epidemiologic project, HERPACC II (Hospital-based Epidemiologic Research Program at Aichi Cancer Center II), including both lifestyle and polymorphism data, following HERPACC-I which solely concentrated on lifestyle data. As of April 2001, about 3000 samples of DNA are being stored to conduct case-control studies. Genotyping of 46 polymorphisms has been conducted at the laboratory of the Division of Epidemiology and Prevention. Twelve case-control studies and two papers on a new PCR method, PCR-CTPP (polymerase chain reaction with confronting two-pair primers), have been accepted for publication. Significant findings in Japanese were found for 1) gene-environment interaction for esophageal cancer between heavy drinking and aldehyde dehydrogenase 2 (ALDH2), 2) malignant lymphoma risk with methylenetetrahydrofalate reductase (MTHFR) and methionine synthase (MS), 3) interactions between smoking and two polymorphisms, interleukin 1B (IL-1B) and myeloperoxidase (MPO) for Helicobacter pylori infection, and 4) smoking habits with dopamine receptor D2 (DRD2) and IL-1B. Further studies on interactions with polymorphisms will continue to be conducted for Japanese, using larger sizes of samples.

A Model of Practical Cancer Prevention for Out-patients Visiting a Hospital: the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC).

To promote a cancer prevention program at hospital, we started the hospital-based epidemiologic research program at Aichi Cancer Center (HERPACC) in 1988. Because patients visiting hospitals are very concerned not only about their own health condition but also practical way of disease prevention, we consider outpatients, especially those free of cancer, as ideal targets to make a model program and a practical cancer prevention strategy for general people. To confirm risk and protective effects of lifestyle factors like dietary habits, smoking and drinking, and exercise on cancer in Japanese, we have been undertaking large-scale case-referent comparative studies of main cancer sites (stomach, colorectal, lung, breast and uterine cancers) using the data generated by HERPACC. The risk of respiratory tract cancer was definitely elevated by habitual smoking and that of upper digestive tract cancer by combined habitual smoking and drinking. Frequent intake of raw vegetables and/or fruit in contrast reduced the risk of lung cancer among smokers. Current obesity was positively associated with risk of post-menopausal breast cancer, recently on the increase in Japan. However, all sites of cancer were linearly decreased with frequency of exercise in both males and females. Based on these pieces of evidence and other main results obtained from the HERPACC studies, prevention trials with provision of information about protective and risk factors for main sites of cancers to outpatients have been planned in parallel to continuation of HERPACC.