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Jo L Freudenheim

Publications and source records attributed to Jo L Freudenheim.

At least 19 recordsLinked to original sources

Lifetime adult weight gain, central adiposity, and the risk of pre- and postmenopausal breast cancer in the Western New York exposures and breast cancer study.

While there are quite consistent data regarding associations of body weight and postmenopausal breast cancer, there are now accumulating data that would indicate that weight gain in adult life is more predictive of risk than absolute body weight. There is, however, little known about the relative impact of timing of weight gain in adult life as well as other characteristics of the weight and breast cancer association that might provide insight into the mechanism of the observation. We conducted a population-based case control study of breast cancer (1996-2001), the Western New York Exposures and Breast Cancer Study. Included were 1,166 women with primary, histologically confirmed, incident breast cancer and 2,105 controls frequency-matched on age, race and county of residence. Unconditional logistic regression was used to estimate odds ratios and 95% confidence intervals. We found increased risk of breast cancer associated with lifetime adult weight gain among post- but not premenopausal women, and there was a 4% increase in risk for each 5 kg increase in adult weight. Further there was a tendency toward a stronger association for those with higher waist circumference and those with positive estrogen or progesterone status, and who had never used HRT. We also found an association with risk for weight gain since first pregnancy and for weight gain between the time of the first pregnancy and menopause, independent of body mass index and lifetime adult weight gain. Our results suggest that there are time periods of weight gain that have greater impact on risk, and that central body fat, receptor status and hormone replacement therapy may all affect the observed association.

Adiposity↗

Dietary carotenoids and risk of colorectal cancer in a pooled analysis of 11 cohort studies.

Dietary carotenoids have been hypothesized to protect against epithelial cancers. The authors analyzed the associations between intakes of specific carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein + zeaxanthin, and lycopene) and risk of colorectal cancer using the primary data from 11 cohort studies carried out in North America and Europe. Carotenoid intakes were estimated from food frequency questionnaires administered at baseline in each study. During 6-20 years of follow-up between 1980 and 2003, 7,885 incident cases of colorectal cancer were diagnosed among 702,647 participants. The authors calculated study-specific multivariate relative risks and then combined them using a random-effects model. In general, intakes of specific carotenoids were not associated with colorectal cancer risk. The pooled multivariate relative risks of colorectal cancer comparing the highest quintile of intake with the lowest ranged from 0.92 for lutein + zeaxanthin to 1.04 for lycopene; only for lutein + zeaxanthin intake was the result borderline statistically significant (95% confidence interval: 0.84, 1.00). The associations observed were generally similar across studies, for both sexes, and for colon cancer and rectal cancer. These pooled data did not suggest that carotenoids play an important role in the etiology of colorectal cancer.

Carotenoids↗

Intake of the major carotenoids and the risk of epithelial ovarian cancer in a pooled analysis of 10 cohort studies.

Carotenoids, found in fruits and vegetables, have the potential to protect against cancer because of their properties, including their functions as precursors to vitamin A and as antioxidants. We examined the associations between intakes of alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein/zeaxanthin and lycopene and the risk of invasive epithelial ovarian cancer. The primary data from 10 prospective cohort studies in North America and Europe were analyzed and then pooled. Carotenoid intakes were estimated from a validated food frequency questionnaire administered at baseline in each study. Study-specific relative risks (RR) were estimated using the Cox proportional hazards model and then combined using a random-effects model. Among 521,911 women, 2,012 cases of ovarian cancer occurred during a follow-up of 7-22 years across studies. The major carotenoids were not significantly associated with the risk of ovarian cancer. The pooled multivariate RRs (95% confidence intervals) were 1.00 (0.95-1.05) for a 600 microg/day increase in alpha-carotene intake, 0.96 (0.93-1.03) for a 2,500 microg/day increase in beta-carotene intake, 0.99 (0.97-1.02) for a 100 microg/day increase in beta-cryptoxanthin intake, 0.98 (0.94-1.03) for a 2,500 microg/day increase in lutein/zeaxanthin intake and 1.01 (0.97-1.05) for a 4,000 microg/day increase in lycopene intake. These associations did not appreciably differ by study (p-values, tests for between-studies heterogeneity >0.17). Also, the observed associations did not vary substantially by subgroups of the population or by histological type of ovarian cancer. These results suggest that consumption of the major carotenoids during adulthood does not play a major role in the incidence of ovarian cancer.

Breast Neoplasms↗

Lifetime cumulative exposure to secondhand smoke and risk of myocardial infarction in never smokers: results from the Western New York health study, 1995-2001.

BACKGROUND: Although many epidemiologic studies have investigated the association between exposure to secondhand smoke (SHS) and risk of coronary heart disease (CHD), few of these studies have assessed exposure measures from different sources over a lifetime. Therefore, we sought to test the association between lifetime cumulative exposure to SHS and risk of myocardial infarction (MI) (as an indication of CHD) among never smokers. METHODS: A population-based case-control study in which participants were 1541 never smokers (284 cases and 1257 controls) drawn from 1197 women and men with incident MI and 2850 healthy controls (aged 35-70 years) identified from 2 Western New York counties between 1995 and 2001. Study subjects were asked to report their exposure to SHS at home, at work, and in public settings from childhood to their present age. Exposure histories from each source were combined to form a cumulative lifetime exposure measure. Multiple logistic regression analysis estimated the association between SHS exposure and case status adjusted for age, sex, education, body mass index, race, drinking status, lifetime physical activity, hypertension, diabetes mellitus, and hypercholesterolemia. RESULTS: After adjustment for covariates, exposure to SHS was not significantly associated with an increased risk of MI. Compared with participants in the bottom tertile of SHS exposure, those in the top tertile had an odds ratio of 1.19 [95% confidence interval, 0.78-1.82] for MI. Virtually all subjects reported some exposure to SHS over their lifetime, but self-reported exposures declined over time, especially in the period closest to the interview. CONCLUSIONS: Exposure to SHS has declined sharply among nonsmokers in recent years. In the absence of high levels of recent exposure to SHS, cumulative lifetime exposure to SHS may not be as important a risk factor for MI as previously thought.

Adult↗

Association between anemia and quality of life in a population sample of individuals with chronic obstructive pulmonary disease.

BACKGROUND: Several studies investigated the association of anemia with health related quality of life (HRQL) in patients with chronic disease. However, there is little evidence regarding the association of anemia with HRQL in patients with chronic obstructive pulmonary disease (COPD). METHODS: This is a post-hoc analysis of a study which enrolled a population of adults aged 35-79 randomly selected from residents of Erie and Niagara Counties, NY, between 1996 and 2000. In addition to demographic information and physical measurements, we obtained spirometry data and hemoglobin levels. We used modified Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria to define COPD, and World Health Organization (WHO) criteria to define anemia. To assess HRQL we used the Short Form-36 (SF-36) to assess physical functioning (PF), physical component summary (PCS) measures and mental component summary (MCS) measures. RESULTS: In the entire study population (n = 2704), respondents with anemia had lower scores on the physical functioning domain [45.4 (SD10.9) vs. 49.2 (SD 9.1); p < 0.0001]. Among patients with COPD (n = 495) the PF scores (39.9 vs. 45.4) and the PCS (41.9 vs. 45.9) were significantly lower in individuals with anemia compared to those without. In multiple regression analysis, the association between hemoglobin and PCS was positive (regression coefficient 0.02, p = 0.003). There was no significant association of hemoglobin with PF scores or the mental component summary measure after adjusting for covariates in patients with COPD. CONCLUSION: In patients with moderate to very severe COPD anemia may be associated with worse HRQL. However, co-morbidities may explain part or all of this association in these patients.

Adult↗

Methods for pooling results of epidemiologic studies: the Pooling Project of Prospective Studies of Diet and Cancer.

With the growing number of epidemiologic publications on the relation between dietary factors and cancer risk, pooled analyses that summarize results from multiple studies are becoming more common. Here, the authors describe the methods being used to summarize data on diet-cancer associations within the ongoing Pooling Project of Prospective Studies of Diet and Cancer, begun in 1991. In the Pooling Project, the primary data from prospective cohort studies meeting prespecified inclusion criteria are analyzed using standardized criteria for modeling of exposure, confounding, and outcome variables. In addition to evaluating main exposure-disease associations, analyses are also conducted to evaluate whether exposure-disease associations are modified by other dietary and nondietary factors or vary among population subgroups or particular cancer subtypes. Study-specific relative risks are calculated using the Cox proportional hazards model and then pooled using a random- or mixed-effects model. The study-specific estimates are weighted by the inverse of their variances in forming summary estimates. Most of the methods used in the Pooling Project may be adapted for examining associations with dietary and nondietary factors in pooled analyses of case-control studies or case-control and cohort studies combined.

Diet↗

Dietary lignan intakes and risk of breast cancer by tumor estrogen receptor status.

We examined the association of dietary lignan intake with estrogen receptor negative (ER-) and ER positive (ER+) breast cancer risk in a breast cancer case-control study. Among premenopausal women only, there was a reduced risk of ER- breast cancer for those in the highest compared to the lowest quartile of lignan intake suggesting that the observed negative association of lignans with breast cancer may be limited to ER- tumors.

Adult↗

Intakes of vitamins A, C and E and folate and multivitamins and lung cancer: a pooled analysis of 8 prospective studies.

Intakes of vitamins A, C and E and folate have been hypothesized to reduce lung cancer risk. We examined these associations in a pooled analysis of the primary data from 8 prospective studies from North America and Europe. Baseline vitamin intake was assessed using a validated food-frequency questionnaire, in each study. We calculated study-specific associations and pooled them using a random-effects model. During follow-up of 430,281 persons over a maximum of 6-16 years in the studies, 3,206 incident lung cancer cases were documented. Vitamin intakes were inversely associated with lung cancer risk in age-adjusted analyses; the associations were greatly attenuated after adjusting for smoking and other risk factors for lung cancer. The pooled multivariate relative risks, comparing the highest vs. lowest quintile of intake from food-only, were 0.96 (95% confidence interval (CI) 0.83-1.11) for vitamin A, 0.80 (95% CI 0.71-0.91) for vitamin C, 0.86 (95% CI 0.76-0.99) for vitamin E and 0.88 (95% CI 0.74-1.04) for folate. The association with vitamin C was not independent of our previously reported inverse association with beta-cryptoxanthin. Further, vitamin intakes from foods plus supplements were not associated with a reduced risk of lung cancer in multivariate analyses, and use of multivitamins and specific vitamin supplements was not significantly associated with lung cancer risk. The results generally did not differ across studies or by sex, smoking habits and lung cancer cell type. In conclusion, these data do not support the hypothesis that intakes of vitamins A, C and E and folate reduce lung cancer risk.

Antioxidants↗

A pooled analysis of 12 cohort studies of dietary fat, cholesterol and egg intake and ovarian cancer.

Fat and cholesterol are theorized to promote ovarian carcinogenesis by increasing circulating estrogen levels. Although case-control studies have reported positive associations between total and saturated fat intake and ovarian cancer risk, two cohort studies have observed null associations. Dietary cholesterol and eggs have been positively associated with ovarian cancer risk. A pooled analysis was conducted on 12 cohort studies. Among 523,217 women, 2,132 incident epithelial ovarian cancer cases were identified. Study-specific relative risks (RR) and 95% confidence intervals (CI) were calculated by Cox proportional hazards models, and then pooled using a random effects model. Total fat intake was not associated with ovarian cancer risk (pooled multivariate RR = 1.08, 95% CI 0.86-1.34 comparing > or =45 to 30-<35% of calories). No association was observed for monounsaturated, polyunsaturated, trans-unsaturated, animal and vegetable fat, cholesterol and egg intakes with ovarian cancer risk. A weakly positive, but non-linear association, was observed for saturated fat intake (pooled multivariate RR = 1.29, 95% CI: 1.01-1.66 comparing highest versus lowest decile). Results for histologic subtypes were similar. Overall, fat, cholesterol and egg intakes were not associated with ovarian cancer risk. The positive association for saturated fat intake at very high intakes merits further investigation.

Cholesterol↗

Perinatal exposures and breast cancer risk in the Western New York Exposures and Breast Cancer (WEB) Study.

BACKGROUND: There is increasing evidence that early life exposures, such as birth weight, infant feeding practices, birth rank and maternal age at delivery may play a role in breast carcinogenesis. METHODS: We conducted a case-control study of women aged 35-80 in Western New York (Western New York Exposure and Breast Cancer Study, the WEB Study, 1996-2001). The study included 845 women diagnosed with primary, incident, histologically confirmed breast cancer, and 1538 controls frequency-matched to cases on age, race, and county of residence. We conducted extensive in-person interviews including self-reported birth weight, history of having been breastfed, birth rank, and maternal age at delivery. RESULTS: Birth weight was significantly associated with pre- but not post-menopausal breast cancer risk. Compared to women whose birth weight was 5.5-7 pounds, we found an increased risk associated with a birth weight greater than 8.5 pounds (OR 1.84, 95%CI: 1.12-3.02). Risk was also increased for pre- but not post-menopausal women who had not been breastfed (OR 1.78, 95%CI: 1.21-2.60). Birth order and maternal age at delivery were not significantly associated with breast cancer risk. CONCLUSIONS: Our findings are consistent with other studies showing breast cancer risk associated with birth weight for pre- but not post-menopausal breast cancer. As we found in an earlier study, having been breastfed was associated with decreased risk. These findings add to the accumulating evidence that early life events impact women's subsequent breast cancer risk.

Adult↗

Lifetime alcohol drinking pattern is related to the prevalence of metabolic syndrome. The Western New York Health Study (WNYHS).

The association of lifetime alcohol drinking pattern with the prevalence of the metabolic syndrome is largely unknown. Analyses were conducted on a population-based sample in a cross-sectional study (N=2818, ages 35-79 years, 93% whites). Included were subjects who drank at least once a month for a period of at least six months during their lifetimes and were free of cardiovascular disease and cancer at the time of interview. Lifetime drinking measures included total years of drinking, total drinking days, volume (total drinks) and average intensity (#drinks/drinking day); frequency of intoxication and heavy drinking; and age drinking began and ended. Metabolic syndrome components included impaired fasting glucose (IFG), high triglycerides (HTG), low HDL cholesterol (LHDLC), abdominal obesity (ABO), and hypertension (HBP). Potential confounders examined were age, gender, race, family history of coronary heart disease or diabetes, years of education, lifetime and current cigarette smoking, current drinking status, physical activity, and dietary factors. Multiple logistic regressions indicated that average intensity was directly related to IFG, HTG, HBP, and metabolic syndrome overall (p for linear trend=0.03, 0.04, 0.003, and 0.009, respectively) and to ABO in women only (p for trend=0.0004). Prevalence ratios (95% CI) for the metabolic syndrome according to quartiles of intensity were 1.00 (lowest), 1.23 (0.91-1.67), 1.43 (1.06-1.91) and 1.60 (1.12-2.30). Total drinking days was inversely related to LHDLC (p for trend=0.0002) and to ABO in women only (p for trend<0.0001). It is concluded that lifetime drinking patterns are significantly related to the prevalence of the metabolic syndrome.

Abdominal Fat↗

Alcohol drinking pattern and subjective health in a population-based study.

AIMS: Some patterns of alcohol consumption (e.g. binge drinking, drinking outside of meals) have been associated with detrimental effects on health outcomes. Subjective health provides a global assessment of health status and is a strong predictor of total mortality; however, little is known about its relationship with alcohol drinking pattern. The association between several drinking patterns (i.e. drinking intensity and frequency, frequency of intoxication, drinking outside of meals, and beverage type) and subjective health was examined in a random sample of 3586 women and men. DESIGN: A population-based cross-sectional study. METHODS: Subjective health was assessed using the physical and mental health component summaries of the Short Form-36 health survey questionnaire. Alcohol consumption refers to the 30 days before the interview. Analysis of covariance compared gender-specific mean scores across alcohol drinking patterns. FINDINGS: Overall, non-current drinkers reported poorer physical and mental health than life-time abstainers and current drinkers, while no consistent differences were found between life-time abstainers and current drinkers. In female current drinkers, daily drinking, beer and mixed beverage consumption were associated with better mental health. In male current drinkers, moderate alcohol consumption (2-2.9 drinks per day), wine and mixed beverage consumption were associated with better physical health. Intoxication and liquor consumption were associated with poorer mental health in women and poorer physical health in men. No consistent associations were found for drinking outside meals. CONCLUSIONS: Aspects of drinking pattern may affect subjective health differentially in women and men. Overall, intoxication and liquor drinking are associated with poorer self-perceived health status than regular, moderate consumption of other alcoholic beverages.

Adult↗

p53 Mutation analysis in breast tumors by a DNA microarray method.

The p53 gene acts as a regulator of cell growth and DNA repair in normal cells; inactivation of the gene seems to lead to cancer. It is the most commonly mutated gene in human cancers, and a high-throughput sequencing method is needed for cancer etiology studies using large sample sets. In our population-based case-control study of breast cancer, the p53 gene was amplified by PCR for 392 subjects from seven hospitals in Western New York using the Affymetrix GeneChip technology. One hundred thirty-eight (35%) of the breast tumors had p53 mutations, of which 88% were located in exons 5 to 8. New hotspots were identified at codons 179, 195, 196, 213, 217, 249, 254, 278, 281, and 298, and previously reported hotspots were found at codons 175, 248, and 273. Manual sequencing for exons 5 to 9 of the p53 gene was done for 139 tumors to validate the Affymetrix assay. The two methods had 100% concordance for mutations detectable by the Affymetrix assay. We also successfully assayed paraffin-embedded breast and lung tumors from as early as 1958 and employed a nested PCR strategy to improve weak PCR amplification. To have statistical power, the investigation of gene environment interactions and cancer requires a large number of tumor analyses, which are frequently only available from archived tissue from multiple sources. We have shown the utility of the Affymetrix GeneChip method under these challenging conditions and provided new data for the mutational spectra of breast cancer in a population-based study.

Breast Neoplasms↗

Dairy products and ovarian cancer: a pooled analysis of 12 cohort studies.

BACKGROUND: Dairy foods and their constituents (lactose and calcium) have been hypothesized to promote ovarian carcinogenesis. Although case-control studies have reported conflicting results for dairy foods and lactose, several cohort studies have shown positive associations between skim milk, lactose, and ovarian cancer. METHODS: A pooled analysis of the primary data from 12 prospective cohort studies was conducted. The study population consisted of 553,217 women among whom 2,132 epithelial ovarian cases were identified. Study-specific relative risks and 95% confidence intervals were calculated by Cox proportional hazards models and then pooled by a random-effects model. RESULTS: No statistically significant associations were observed between intakes of milk, cheese, yogurt, ice cream, and dietary and total calcium intake and risk of ovarian cancer. Higher lactose intakes comparing > or = 30 versus <10 g/d were associated with a statistically significant higher risk of ovarian cancer, although the trend was not statistically significant (pooled multivariate relative risk, 1.19; 95% confidence interval, 1.01-1.40; P(trend) = 0.19). Associations for endometrioid, mucinous, and serous ovarian cancer were similar to the overall findings. DISCUSSION: Overall, no associations were observed for intakes of specific dairy foods or calcium and ovarian cancer risk. A modest elevation in the risk of ovarian cancer was seen for lactose intake at the level that was equivalent to three or more servings of milk per day. Because a new dietary guideline recommends two to three servings of dairy products per day, the relation between dairy product consumption and ovarian cancer risk at these consumption levels deserves further examination.

Calcium, Dietary↗

Pulmonary function and abdominal adiposity in the general population.

BACKGROUND: The prevalence of obesity is increasing, and there is evidence that obesity, in particular abdominal obesity as a marker of insulin resistance, is negatively associated with pulmonary function. The mechanism for this association and the best marker of abdominal adiposity in relation to pulmonary function is not known. STUDY OBJECTIVE: We assessed the association between pulmonary function and weight, body mass index (BMI), waist circumference, waist/hip ratio, and abdominal height as markers of adiposity and body fat distribution. We used multiple linear regression to analyze the association of pulmonary function (ie, FEV(1) and FVC) [with maneuvers performed in the sitting position] with overall adiposity markers (ie, weight and BMI) and abdominal adiposity markers, stratified by gender, and adjusted for height, age, race, smoking, and other covariates. SETTING AND PARTICIPANTS: A random sample of individuals (n = 2,153) from the general population living in western New York state, 35 to 79 years of age. RESULTS: In women, abdominal height and waist circumference were negatively associated with FEV(1) percent predicted, while all five adiposity markers were negatively associated with FVC percent predicted. In men, all overall and abdominal adiposity markers were inversely associated with FEV(1) percent predicted and FVC percent predicted. CONCLUSION: These results suggest that abdominal adiposity is a better predictor of pulmonary function than weight or BMI, and investigators should consider it when investigating the determinants of pulmonary function.

Abdominal Fat↗

Dietary fiber intake and risk of colorectal cancer: a pooled analysis of prospective cohort studies.

CONTEXT: Inconsistent findings from observational studies have continued the controversy over the effects of dietary fiber on colorectal cancer. OBJECTIVE: To evaluate the association between dietary fiber intake and risk of colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS: From 13 prospective cohort studies included in the Pooling Project of Prospective Studies of Diet and Cancer, 725,628 men and women were followed up for 6 to 20 years across studies. Study- and sex-specific relative risks (RRs) were estimated with the Cox proportional hazards model and were subsequently pooled using a random-effects model. MAIN OUTCOME MEASURE: Incident colorectal cancer. RESULTS: During 6 to 20 years of follow-up across studies, 8081 colorectal cancer cases were identified. For comparison of the highest vs lowest study- and sex-specific quintile of dietary fiber intake, a significant inverse association was found in the age-adjusted model (pooled RR = 0.84; 95% confidence interval [CI], 0.77-0.92). However, the association was attenuated and no longer statistically significant after adjusting for other risk factors (pooled multivariate RR = 0.94; 95% CI, 0.86-1.03). In categorical analyses compared with dietary fiber intake of 10 to <15 g/d, the pooled multivariate RR was 1.18 (95% CI, 1.05-1.31) for less than 10 g/d (11% of the overall study population); and RR, 1.00 (95% CI, 0.85-1.17) for 30 or more g/d. Fiber intake from cereals, fruits, and vegetables was not associated with risk of colorectal cancer. The pooled multivariate RRs comparing the highest vs lowest study- and sex-specific quintile of dietary fiber intake were 1.00 (95% CI, 0.90-1.11) for colon cancer and 0.85 (95% CI, 0.72-1.01) for rectal cancer (P for common effects by tumor site = .07). CONCLUSIONS: In this large pooled analysis, dietary fiber intake was inversely associated with risk of colorectal cancer in age-adjusted analyses. However, after accounting for other dietary risk factors, high dietary fiber intake was not associated with a reduced risk of colorectal cancer.

Colorectal Neoplasms↗

Oxidative stress and pulmonary function in the general population.

Studies have shown increased oxidative stress in patients with chronic airflow limitation; however, the population-based evidence for the association of oxidative stress with pulmonary function is limited. The authors analyzed the association of plasma thiobarbituric acid-reactive substances (TBARS), glutathione, glutathione peroxidase, and 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox)-equivalent antioxidant capacity with forced expiratory volume in 1 second and forced vital capacity using data collected from 1996 to 2000 in a general population sample from western New York State (n = 2,346). After adjustment for covariates including smoking status, lifetime pack-years of smoking, education, weight, and eosinophils, multivariate analysis showed an inverse association of TBARS with forced expiratory volume in 1 second and forced vital capacity as the percentage of the predicted value (FEV1% and FVC%, respectively), positive associations of glutathione peroxidase with FEV1% and FVC%, and an inverse association of glutathione with FEV1% in men (p < 0.05). The associations of TBARS and glutathione peroxidase with FVC% in men remained statistically significant after adjustment for serum carotenoid levels. There were no statistically significant associations of oxidative stress with pulmonary function in women. These results suggest that oxidative stress may be associated with airflow limitation in men, and that gender differences may exist in the relation of oxidative stress to pulmonary function.

Biomarkers↗

Accurate genotyping from paraffin-embedded normal tissue adjacent to breast cancer.

Genetic polymorphism analysis for disease risk is widely used in epidemiology studies; blood or oral cavity cells are the most widely used source of DNA. However, these types of samples are not always available, particularly for studies that were conducted years ago. An alternative potential source of patient DNA exists in the form of paraffin-embedded normal tissue adjacent to tumor samples, which are collected and stored routinely for clinical use. The use of such samples can be conceptually problematic, however, due to the presence of field cancerization in the surrounding normal tissue, with the possible presence of chromosomal loss. Specifically, loss of heterozygosity (LOH) might bias the genotyping results and cause genotype misclassification. However, field cancerization and LOH might not be an issue because LOH is not easily found unless there is careful microdissection of only tumor cells (leaving stromal, inflammatory and fat cells), for example, laser-capture microdissection. In this study, we set out to determine the degree of genotype misclassification from normal tissues adjacent to tumors, if any, by comparing these results with blood genotyping. We examined samples from 106 subjects with breast cancer, analyzing five different genotypes selected from regions commonly known to have LOH in breast cancer. These genotypes were methylenetetrahydrofolate reductase (MTHFR), oxoguanosine glycosylase 1 (hOGG1), dopamine beta-hydroxylase (DBH), dopamine receptor D2 (DRD2) and NAD(P)H dehydrogenase quinone 1 (NQO1), conducted by using real-time PCR and TaqMan genotyping analyses. We found that among these five genotypes and 106 comparisons, there was a 100% concordance for genotyping from normal tissue adjacent to tumor and from blood. Our findings indicate that the use of adjacent normal tissues provides accurate genotyping results with high specificity. Although this study only used breast tumor samples, and may be applicable only to breast cancer studies, we expect the results to be applicable to other types of cancers also.

Biopsy↗