Gail Garbowski - Academia.edu (original) (raw)

Papers by Gail Garbowski

Research paper thumbnail of WIC AND SOMATIC AND PSYCHOLOGICAL DEVELOPMENT OF PRE SCHOOL CHILDREN: THE NATIONAL WIC EVALUATION

Pediatric Research, 1984

Einstein College o f Medicine, Dept. of P e d i a t r i c s , Bronx, NY. W e r e l a t e d age of... more Einstein College o f Medicine, Dept. of P e d i a t r i c s , Bronx, NY. W e r e l a t e d age of onset of b e n e f i t s from t h e Special Supplement a l Food Program f o r Women, I n f a n t s and Children (WIC) t o h e i g h t , welght, Q u e t e l e t ' s index (wt/length2), head circumference, mldarm circumference and t r i c e p s and subscapular skinfold thickness among 2 1 4 2 representative poor children under f l v e from 59 a r e a s nationwide and behavior and cognition among 486 four and f i v e year o l d s . W e used S c h a e f f e r ' s I n f a n t Behavior Inventory, t h e Peahody Picture Vocabulary t e s t and the forward and backward d i g i t memory t e s t s from t h e McCarthy Scale of I n f a n t Development. W e c o n t r o l l e d f o r age and sex, and then f o r a wide range of additiona l s o c i a l , demographic and somatic c o v a r i a t e s . Highly significant improvements i n c h i l d r e n ' s d i e t s by WIC were not r e f l e c t e d by advantages i n l i n e a r growth. WIC p a r t i c i p a n t s were s i g n i f l c a n t l y s h o r t e r than c o n t r o l s (0.8 cm). Early WIC rec r u i t s had no p a r a l l e l decrease i n head circumference. We conclude t h a t a ) t h e WIC program i s t a r g e t e d t o appropriate ( s h o r t and deprived) children; b) i d e n t i f y i n g adequate c o n t r o l s f o r WIC recipients may now be impossible, with t h e wide d i f f u s i o n of the program; c ) it is unlikely t h a t WIC b e n e f i t s had any e f f e c t on l l n e a r growth; dl e a r l y WIC b e n e f i t s had some b e n e f i c i a l e f f e c t on l a t e r head, and presumably, b r a i n growth. Prenatal WIC recipi e n t s had s i g n i f i c a n t l y b e t t e r performance on the PPVT, and l a t e r r e c r u i t s had s i g n i f i c a n t l y b e t t e r (backward) d i g i t memory. There were no s i g n i f i c a n t d i f f e r e n c e s i n c h i l d behavior. The implicat i o n s of these observations w l l l be discussed. MATERNAL SELF-ESTEEM AND MASTERY IN RELATION TO 104 INFANT BIRTHWEIGHT. J i l l Schlansker, Marilyn Escobedo. Cheryl Cipriani , Carolyn McLerran, Maria R e n d o n . (Spon. by YW Brans). The Univ of TX Health Science Ctr a t San Antonio and Brooke Army Med C t r , Dept of P e d i a t r i c s , San Antonio and Ft. Sam Houston, TX

Research paper thumbnail of Global DNA Methylation, Measured by the Luminometric Methylation Assay (LUMA), Associates with Postmenopausal Breast Cancer in Non-Obese and Physically Active Women

Journal of Cancer, 2015

Little is known about how modifiable lifestyle factors interact with the epigenome to influence d... more Little is known about how modifiable lifestyle factors interact with the epigenome to influence disease. Body mass index (BMI, weight kg/height m2) and physical activity are associated with postmenopausal breast cancer, but the mechanisms are not well-understood. We hypothesized that BMI or physical activity may modify the association between markers of global DNA methylation and postmenopausal breast cancer risk. Resources from a population-based case-control study (~1300 postmenopausal women) were used to construct logistic regression models. We explored whether the association between breast cancer and global methylation, assessed using the luminometric methylation assay (LUMA) and long interspersed elements-1 (LINE-1) methylation in white blood cell DNA, was modified by BMI or recreational physical activity (RPA). The LUMA-breast cancer association was modified by BMI (multiplicative p=0.03) and RPA (p=0.004). Non-obese women in the highest quartile of LUMA experienced a greater...

Research paper thumbnail of Gene-Specific Promoter Methylation Status in Hormone-Receptor-Positive Breast Cancer Associates with Postmenopausal Body Size and Recreational Physical Activity

International journal of cancer and clinical research

Breast cancer, the leading cancer diagnosis among American women, is positively associated with p... more Breast cancer, the leading cancer diagnosis among American women, is positively associated with postmenopausal obesity and little or no recreational physical activity (RPA). However, the underlying mechanisms of these associations remain unresolved. Aberrant changes in DNA methylation may represent an early event in carcinogenesis, but few studies have investigated associations between obesity/RPA and gene methylation, particularly in postmenopausal breast tumors where these lifestyle factors are most relevant. We used case-case unconditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CI) for the associations between body mass index (BMI=weight [kg]/height [m(2)]) in the year prior to diagnosis, or RPA (average hours/week), and methylation status (methylated vs. unmethylated) of 13 breast cancer-related genes in 532 postmenopausal breast tumor samples from the Long Island Breast Cancer Study Project. We also explored whether the association betwe...

Research paper thumbnail of Abstract LB-290: The influence of body size and weight gain on global and gene promoter methylation in a population-based breast cancer study

Research paper thumbnail of Environmental toxins and breast cancer on Long Island. I. Polycyclic aromatic hydrocarbon DNA adducts

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2002

Polycyclic aromatic hydrocarbons (PAH) are potent mammary carcinogens in rodents, but their effec... more Polycyclic aromatic hydrocarbons (PAH) are potent mammary carcinogens in rodents, but their effect on breast cancer development in women is not clear. To examine whether currently measurable PAH damage to DNA increases breast cancer risk, a population-based case-control study was undertaken on Long Island, NY. Cases were women newly diagnosed with in situ and invasive breast cancer; controls were randomly selected women frequency matched to the age distribution of cases. Blood samples were donated by 1102 (73.0%) and 1141 (73.3%) of case and control respondents, respectively. Samples from 576 cases and 427 controls were assayed for PAH-DNA adducts using an ELISA. The geometric mean (and geometric SD) of the log-transformed levels of PAH-DNA adducts on a natural scale was slightly, but nonsignificantly, higher among cases [7.36 (7.29)] than among controls [6.21 (4.17); P = 0.51]. The age-adjusted odds ratio (OR) for breast cancer in relation to the highest quintile of adduct levels c...

Research paper thumbnail of Leisure and occupational physical activity and risk of colorectal adenomatous polyps

International Journal of Cancer, 1996

Multiple studies have shown a protective effect for physical activity on the incidence of colorec... more Multiple studies have shown a protective effect for physical activity on the incidence of colorectal cancer, but few have addressed its association with incident adenomas and none have investigated its association with metachronous adenomas. We interviewed 2,001 patients undergoing colonoscopy in 3 New York City practices between 1986-1988. Of these, 298 had a first diagnosis of adenomas, 506 had normal colonoscopies, 197 had metachronous adenomas and 345 had normal colonoscopies with a past history of adenomas. Subjects were queried regarding use of moderate amounts of recreational exercise (swimming, jogging, biking, racket sports and other sports) on a regular basis, and were also asked to estimate their level of physical activity. Occupational physical activity was assessed through a blinded coding of occupational titles. After adjusting for age, years of education, body mass index, total caloric intake, dietary fiber intake, dietary fat intake and years of cigarette smoking, protective effects of borderline significance were observed among males for leisure physical activity for metachronous and incident cases. Occupational physical activity was found to be significantly protective in male incident cases. Men with increased levels of either occupational or leisure activity showed a reduction for incident and metachronous cases. No effects were observed for females. Thus, in this study, both leisure and occupational physical activity were associated with a reduced risk of incident and metachronous adenomas among men but not women.

Research paper thumbnail of Helicobacter pylori and colorectal neoplasia: Evidence against an association

Research paper thumbnail of Incidence and recurrence rates of colorectal adenomas: A prospective study

Research paper thumbnail of Associations between Polycyclic Aromatic Hydrocarbon–Related Exposures and p53 Mutations in Breast Tumors

Environmental Health Perspectives, 2009

Research paper thumbnail of Coronary artery disease and colorectal neoplasia

Diseases of the Colon & Rectum, 1995

This study was designed to determine whether patients with coronary artery disease are at elevate... more This study was designed to determine whether patients with coronary artery disease are at elevated risk for colorectal neoplasia. A case-control study was conducted among consecutive patients in three colonoscopy practices in New York City from 1986 to 1988. All study participants completed an interview questionnaire covering demographics, diet, environmental and behavioral exposures, family and personal medical history, and other variables. For the present study, 298 newly diagnosed colorectal adenoma cases and 107 incident cancer cases were compared with 507 colonoscoped controls without colorectal neoplasia or other significant findings on colonoscopy. Data on history of coronary artery disease (angina and/or heart attack) were obtained solely from the study participants' questionnaire responses. No association was observed between angina, heart attack, or either and colorectal adenomas in males. However, prior coronary artery disease was found to be associated with colorectal cancer in males more than 60 years of age and with colorectal adenomas in females aged 50 years or younger. Men with coronary artery disease may be at elevated risk for subsequent colorectal cancer. Young women with coronary artery disease also may be at elevated risk for colorectal neoplasia.

Research paper thumbnail of Evaluation of 4-aminobiphenyl-DNA adducts in human breast cancer: the influence of tobacco smoke

Carcinogenesis, 2003

Breast cancer is one of the major cancers around the world but its etiology is still not well und... more Breast cancer is one of the major cancers around the world but its etiology is still not well understood. Only~50% of the disease is associated with known risk factors including highly penetrant genes and lifestyle factors. Thus, environmental carcinogens may play an important role in the etiology of breast cancer. The arylamine 4-aminobiphenyl (4-ABP) is a tobacco smoke constituent, an environmental contaminant, and a well-established bladder carcinogen in rodents and humans. In this study, we investigated the role of 4-ABP in the etiology of human breast cancer by measuring 4-ABP±DNA adducts using a monoclonal antibody based immunoperoxidase method that had been validated by comparison with gas chromatography/mass spectroscopy analysis of liver tissues from 4-ABP-treated mice. Adducts were analyzed in 150 paraffin-embedded breast tumors and in 55 adjacent normal tissues collected from cases in the Long Island Breast Cancer Study Project. The role of polymorphisms in genes involved in the metabolism of 4-ABP including N-acetyl transferase 2 (NAT2), cytochrome P4501A2 (CYP1A2) and glutathione S-transferase M1 (GSTM1) and the nucleotide excision repair gene XPD was also explored in the same patients. The mean logtransformed relative staining intensity for 4-ABP±DNA adducts was higher in normal (5.93 AE 0.54) than in the corresponding tumor (5.44 AE 0.62, P 5 0.0001) tissues. However, a highly significant positive correlation was observed between the levels of 4-ABP±DNA in both tissues (r 0.72, P 5 0.0001). Smoking status was correlated with the levels of 4-ABP±DNA in tumor adjacent normal tissues with a significant linear trend (P 0.04) for current, former and never smokers; adducts were not related to smoking status in tumor tissues. No correlation was observed between the levels of 4-ABP±DNA and polymorphisms in the genes analyzed even when subjects were stratified by smoking status. These results demonstrate that smoking is associated with increased levels of 4-ABP±DNA adducts in human mammary tissue. In this study, genetic polymorphisms did not significantly affect the formation of 4-ABP±DNA adducts in breast cancer cases, perhaps due to the small number of samples.

Research paper thumbnail of Levels of p53 antigen in the plasma of patients with adenomas and carcinomas of the colon

Cancer Letters, 1995

Plasma levels of p53 protein were examined by an enzyme linked immunosorbent assay in 184 patient... more Plasma levels of p53 protein were examined by an enzyme linked immunosorbent assay in 184 patients enrolled in a colonoscopy study. The mean levels among 47 individuals with normal colonoscopic examinations and no prior history of colonic neoplasia (0.12 ng/ml) and among 61 individuals with normal colonoscopic examinations and a prior history of colonic neoplasia (0.09 ng/ml) were similar. However, the mean levels among 54 individuals with newly diagnosed colonic adenomas (0.44 ng/ml) and 22 individuals with newly diagnosed colonic carcinomas (0.55 ng/ml) were statistically significantly elevated compared to the normal controls (P < 0.02). Among these tumor patients, the plasma levels tended to increase with increasing adenoma size and with increasing carcinoma stage, although these trends were not statistically significant. Defining a significant positive plasma level as any value greater than ten times background, the percentage of positive samples increased from 4% in the controls to 20% in the adenoma cases to 32% in the carcinoma cases. These results demonstrate that plasma p53 protein levels are elevated in a subgroup of individuals with colonic neoplasia.

Research paper thumbnail of Reproductive risk factors for colorectal adenomatous polyps (New York City, NY, United States)

Cancer Causes and Control, 1995

Events of reproductive life, such as parity and age at menarche, have been found in some but not ... more Events of reproductive life, such as parity and age at menarche, have been found in some but not all studies to be associated with risk for colorectal cancer in females. Because adenomatous polyps (adenomas) are precursors of colorectal cancer, we investigated whether reproductive variables were associated with colorectal adenomas. We conducted a case-control study among patients examined in three colonoscopy practices in New York City (NY, United States) from 1986 to 1988. Adenoma cases (n = 128) were defined as women who had an adenoma detected at the index colonoscopy with no history of inflammatory bowel disease, adenomas, or cancer. Controls (n = 283) were women with a normal index colonoscopy and no history of inflammatory bowel disease, adenomas, or cancer. The adjusted odds ratio (OR) for the association of early menarche (age less than 13 years) with adenomas was 0.6 (95 percent confidence interval = 0.4-0.9). Parity, history of spontaneous or induced abortion, infertility, type of menopause, age at menopause, use of oral contraceptives, and use of menopausal hormone replacement therapy were not associated statistically significantly with adenoma risk, although some possible trends were observed. Our findings do not implicate reproductive events, nulliparity, or overexposure to estrogens or to menstrual cycles as mechanisms of increased risk for colorectal neoplasia. Cancer Causes and Control 1995, 6, 513-518

Research paper thumbnail of Cigarette smoking and other behavioral risk factors for recurrence of colorectal adenomatous polyps (New York City, NY, USA)

Cancer Causes & Control, 1994

Adenomatous polyps (hereinafter referred to as adenomas) are known precursors of colorectal cance... more Adenomatous polyps (hereinafter referred to as adenomas) are known precursors of colorectal cancer. Cigarette smoking has been associated with adenomas but not with colorectal cancer, while alcohol and fat intake have been associated with both adenomas and cancer in some studies. Approximately 30 percent of patients with resected adenomas develop another adenoma within three years. This case-control study explores the association of cigarette smoking with adenoma recurrence. Between April 1986 and March 1988, we administered a questionnaire to colonoscoped patients aged 35 to 84 years in three New York City (NY, USA) practices. We compared 186 recurrent polyp cases (130 males, 56 females) and 330 controls (187 males, 143 females) who had a history of polypectomy but normal follow-up colonoscopy, by cigarette-smoking pack-years adjusted for possible confounders. Risk for a metachronous or recurrent adenoma was significantly greater in the highest quartile of smokers than in never-smokers among both men (odds ratio [OR] = 1.8, 95 percent confidence interval [CI] --1.0-3.4) and women (OR = 3.6, CI = 1.7-7.6). Adjustment for time since smoking cessation reduced risk only slightly, as did adjustment for dietary fat intake, which itself remained significant. No association was found between alcohol intake and risk of recurrence. Cigarette smokers appear to have an elevated risk of adenoma recurrence that is not eliminated entirely by smoking cessation. Intervention trials that use adenoma recurrence as an endpoint should take smoking into account.

Research paper thumbnail of Relationship between breast cancer and colorectal adenomatous polyps a case-control study

Cancer, 1992

Although there is a known reciprocal association between breast and colorectal cancer in women, f... more Although there is a known reciprocal association between breast and colorectal cancer in women, few studies have investigated whether a similar association exists between breast cancer and colorectal adenomatous polyps, known to be precursor lesions for colon cancer. A case-control study was conducted on patients in three colonoscopy practices in New York to determine possible risk factors for adenomatous polyps. Among women studied, there were 128 patients with incident adenomatous polyps and 284 control subjects who underwent colonoscopy and had no colorectal neoplasia. No significant association between the incidence of an adenomatous polyp in the colon or rectum and a history of breast cancer was found (odds ratio, 0.71; 95% confidence interval, 0.34 to 1.64). If shared risk factors for breast and colorectal cancer are the reasons for the concurrence of these two malignant lesions, these results suggest that these factors act at the level of promoting adenomatous polyps of the colon and rectum into colorectal cancer.

Research paper thumbnail of The effect of calcium and vitamin supplements on the incidence and recurrence of colorectal adenomatous polyps

Research paper thumbnail of Cholecystectomy as a risk factor for colorectal adenomatous polyps and carcinoma

Cancer, 1991

Multiple studies have suggested a possible relationship between prior cholecystectomy and the occ... more Multiple studies have suggested a possible relationship between prior cholecystectomy and the occurrence of subsequent colorectal carcinoma. This relationship has been particularly noticed among female patients and for right-sided lesions of the colon. In the current study, the authors undertook a case-control study among patients who underwent colonoscopy in three private practices in New York City between April 1986 and March 1988. Over this period, 302 adenomatous polyp cases, 106 colon cancer cases, and 507 controls were interviewed regarding their prior history of cholecystectomy. Overall, no significant association was observed between cholecystectomy and either colorectal adenomatous polyps or cancer. Cholecystectomy does not appear to be a significant risk factor for colorectal neoplasia.

Research paper thumbnail of The Long Island Breast Cancer Study Project: Description of a Multi-Institutional Collaboration to Identify Environmental Risk Factors for Breast Cancer

Breast Cancer Research and Treatment, 2002

The metabolism of the estrogenic hormone is oxidative in nature in contrast to the reductive path... more The metabolism of the estrogenic hormone is oxidative in nature in contrast to the reductive pathway for the neutral steroid hormones.

Research paper thumbnail of Prognostic significance of gene-specific promoter hypermethylation in breast cancer patients

Breast Cancer Research and Treatment, 2012

The association between promoter methylation status and survival was investigated in a large coho... more The association between promoter methylation status and survival was investigated in a large cohort of women with breast cancer, participants in the Long Island Breast Cancer Study Project. Archived tumor tissues (n = 839) were collected from women diagnosed with a first primary invasive or in situ breast cancer in 1996-1997. Vital status was followed through the end of 2005 with a mean follow-up time of 8 years. Promoter methylation of eight breast cancer-related genes was assessed by Methy-Light. The frequencies of methylation for HIN1, RASSF1A, DAPK1, GSTP1, CyclinD2, TWIST, CDH1 and RARb were 62.9, 85.2, 14.1, 27.8, 19.6, 15.3, 5.8 and 27.6%, respectively. Since survival rates of in situ and invasive breast cancers are substantially different, survival analyses were conducted within 670 invasive cases with complete data on all genes. Age-adjusted Cox proportional hazards models revealed that GSTP1, TWIST and RARb methylation was significantly associated with higher breast cancer-specific mortality. Methylation of GSTP1 and RARb was significantly associated with higher all-cause mortality. To investigate the relationship between the number of methylated genes and breast cancer-specific mortality, we included previously published MethyLight data on p16 and APC methylation status. Breast cancer-specific mortality increased in a dose-dependent manner with increasing number of methylated genes (P trend = 0.002), although confidence intervals were wide. Our results suggest that promoter methylation, particularly for a panel of genes, has the potential to be used as a biomarker for predicting prognosis in breast cancer.

Research paper thumbnail of Gene promoter methylation is associated with increased mortality among women with breast cancer

Breast Cancer Research and Treatment, 2010

To better understand breast cancer etiology and progression, we explored the association between ... more To better understand breast cancer etiology and progression, we explored the association between promoter methylation status of three breast cancer related genes (BRCA1, APC and p16) and survival in a large cohort of women with breast cancer. About 800 archived tumor tissues were collected from women diagnosed with a first primary invasive or in situ breast cancer in 1996-1997. The vital status of the participants was followed through the end of year 2005 with a mean follow up time of 8.0 years. Promoter methylation was assessed by methylation-specific PCR (for BRCA1) and MethyLight (for APC and p16). The association of promoter methylation and breast cancer mortality was evaluated by Cox-proportional hazards models. Methylated promoters were found in 59.0%, 48.4% and 3.6% of the tumor samples for BRCA1, APC and p16, respectively. Breast cancer-specific mortality was strongly associated with promoter methylation of p16 [HR and 95% CI: 3.53(1.83-6.78)], whereas the associations with of BRCA1 and APC were less pronounced [HR and 95% CI: 1.81(1.18-2.78) and 1.46(0.98-2.17), respectively]. Similar associations were observed with allcause mortality. As the number of methylated genes increased, the risk of breast cancer-specific mortality also increased in a dose-dependent manner (p, trend=0.01). Importantly, even with our results stratified by hormone receptor status, promoter methylation of the three genes remained predictive of mortality. Our results suggest that promoter methylation could be promising epigenetic markers to be considered for breast cancer survival.

Research paper thumbnail of WIC AND SOMATIC AND PSYCHOLOGICAL DEVELOPMENT OF PRE SCHOOL CHILDREN: THE NATIONAL WIC EVALUATION

Pediatric Research, 1984

Einstein College o f Medicine, Dept. of P e d i a t r i c s , Bronx, NY. W e r e l a t e d age of... more Einstein College o f Medicine, Dept. of P e d i a t r i c s , Bronx, NY. W e r e l a t e d age of onset of b e n e f i t s from t h e Special Supplement a l Food Program f o r Women, I n f a n t s and Children (WIC) t o h e i g h t , welght, Q u e t e l e t ' s index (wt/length2), head circumference, mldarm circumference and t r i c e p s and subscapular skinfold thickness among 2 1 4 2 representative poor children under f l v e from 59 a r e a s nationwide and behavior and cognition among 486 four and f i v e year o l d s . W e used S c h a e f f e r ' s I n f a n t Behavior Inventory, t h e Peahody Picture Vocabulary t e s t and the forward and backward d i g i t memory t e s t s from t h e McCarthy Scale of I n f a n t Development. W e c o n t r o l l e d f o r age and sex, and then f o r a wide range of additiona l s o c i a l , demographic and somatic c o v a r i a t e s . Highly significant improvements i n c h i l d r e n ' s d i e t s by WIC were not r e f l e c t e d by advantages i n l i n e a r growth. WIC p a r t i c i p a n t s were s i g n i f l c a n t l y s h o r t e r than c o n t r o l s (0.8 cm). Early WIC rec r u i t s had no p a r a l l e l decrease i n head circumference. We conclude t h a t a ) t h e WIC program i s t a r g e t e d t o appropriate ( s h o r t and deprived) children; b) i d e n t i f y i n g adequate c o n t r o l s f o r WIC recipients may now be impossible, with t h e wide d i f f u s i o n of the program; c ) it is unlikely t h a t WIC b e n e f i t s had any e f f e c t on l l n e a r growth; dl e a r l y WIC b e n e f i t s had some b e n e f i c i a l e f f e c t on l a t e r head, and presumably, b r a i n growth. Prenatal WIC recipi e n t s had s i g n i f i c a n t l y b e t t e r performance on the PPVT, and l a t e r r e c r u i t s had s i g n i f i c a n t l y b e t t e r (backward) d i g i t memory. There were no s i g n i f i c a n t d i f f e r e n c e s i n c h i l d behavior. The implicat i o n s of these observations w l l l be discussed. MATERNAL SELF-ESTEEM AND MASTERY IN RELATION TO 104 INFANT BIRTHWEIGHT. J i l l Schlansker, Marilyn Escobedo. Cheryl Cipriani , Carolyn McLerran, Maria R e n d o n . (Spon. by YW Brans). The Univ of TX Health Science Ctr a t San Antonio and Brooke Army Med C t r , Dept of P e d i a t r i c s , San Antonio and Ft. Sam Houston, TX

Research paper thumbnail of Global DNA Methylation, Measured by the Luminometric Methylation Assay (LUMA), Associates with Postmenopausal Breast Cancer in Non-Obese and Physically Active Women

Journal of Cancer, 2015

Little is known about how modifiable lifestyle factors interact with the epigenome to influence d... more Little is known about how modifiable lifestyle factors interact with the epigenome to influence disease. Body mass index (BMI, weight kg/height m2) and physical activity are associated with postmenopausal breast cancer, but the mechanisms are not well-understood. We hypothesized that BMI or physical activity may modify the association between markers of global DNA methylation and postmenopausal breast cancer risk. Resources from a population-based case-control study (~1300 postmenopausal women) were used to construct logistic regression models. We explored whether the association between breast cancer and global methylation, assessed using the luminometric methylation assay (LUMA) and long interspersed elements-1 (LINE-1) methylation in white blood cell DNA, was modified by BMI or recreational physical activity (RPA). The LUMA-breast cancer association was modified by BMI (multiplicative p=0.03) and RPA (p=0.004). Non-obese women in the highest quartile of LUMA experienced a greater...

Research paper thumbnail of Gene-Specific Promoter Methylation Status in Hormone-Receptor-Positive Breast Cancer Associates with Postmenopausal Body Size and Recreational Physical Activity

International journal of cancer and clinical research

Breast cancer, the leading cancer diagnosis among American women, is positively associated with p... more Breast cancer, the leading cancer diagnosis among American women, is positively associated with postmenopausal obesity and little or no recreational physical activity (RPA). However, the underlying mechanisms of these associations remain unresolved. Aberrant changes in DNA methylation may represent an early event in carcinogenesis, but few studies have investigated associations between obesity/RPA and gene methylation, particularly in postmenopausal breast tumors where these lifestyle factors are most relevant. We used case-case unconditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CI) for the associations between body mass index (BMI=weight [kg]/height [m(2)]) in the year prior to diagnosis, or RPA (average hours/week), and methylation status (methylated vs. unmethylated) of 13 breast cancer-related genes in 532 postmenopausal breast tumor samples from the Long Island Breast Cancer Study Project. We also explored whether the association betwe...

Research paper thumbnail of Abstract LB-290: The influence of body size and weight gain on global and gene promoter methylation in a population-based breast cancer study

Research paper thumbnail of Environmental toxins and breast cancer on Long Island. I. Polycyclic aromatic hydrocarbon DNA adducts

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2002

Polycyclic aromatic hydrocarbons (PAH) are potent mammary carcinogens in rodents, but their effec... more Polycyclic aromatic hydrocarbons (PAH) are potent mammary carcinogens in rodents, but their effect on breast cancer development in women is not clear. To examine whether currently measurable PAH damage to DNA increases breast cancer risk, a population-based case-control study was undertaken on Long Island, NY. Cases were women newly diagnosed with in situ and invasive breast cancer; controls were randomly selected women frequency matched to the age distribution of cases. Blood samples were donated by 1102 (73.0%) and 1141 (73.3%) of case and control respondents, respectively. Samples from 576 cases and 427 controls were assayed for PAH-DNA adducts using an ELISA. The geometric mean (and geometric SD) of the log-transformed levels of PAH-DNA adducts on a natural scale was slightly, but nonsignificantly, higher among cases [7.36 (7.29)] than among controls [6.21 (4.17); P = 0.51]. The age-adjusted odds ratio (OR) for breast cancer in relation to the highest quintile of adduct levels c...

Research paper thumbnail of Leisure and occupational physical activity and risk of colorectal adenomatous polyps

International Journal of Cancer, 1996

Multiple studies have shown a protective effect for physical activity on the incidence of colorec... more Multiple studies have shown a protective effect for physical activity on the incidence of colorectal cancer, but few have addressed its association with incident adenomas and none have investigated its association with metachronous adenomas. We interviewed 2,001 patients undergoing colonoscopy in 3 New York City practices between 1986-1988. Of these, 298 had a first diagnosis of adenomas, 506 had normal colonoscopies, 197 had metachronous adenomas and 345 had normal colonoscopies with a past history of adenomas. Subjects were queried regarding use of moderate amounts of recreational exercise (swimming, jogging, biking, racket sports and other sports) on a regular basis, and were also asked to estimate their level of physical activity. Occupational physical activity was assessed through a blinded coding of occupational titles. After adjusting for age, years of education, body mass index, total caloric intake, dietary fiber intake, dietary fat intake and years of cigarette smoking, protective effects of borderline significance were observed among males for leisure physical activity for metachronous and incident cases. Occupational physical activity was found to be significantly protective in male incident cases. Men with increased levels of either occupational or leisure activity showed a reduction for incident and metachronous cases. No effects were observed for females. Thus, in this study, both leisure and occupational physical activity were associated with a reduced risk of incident and metachronous adenomas among men but not women.

Research paper thumbnail of Helicobacter pylori and colorectal neoplasia: Evidence against an association

Research paper thumbnail of Incidence and recurrence rates of colorectal adenomas: A prospective study

Research paper thumbnail of Associations between Polycyclic Aromatic Hydrocarbon–Related Exposures and p53 Mutations in Breast Tumors

Environmental Health Perspectives, 2009

Research paper thumbnail of Coronary artery disease and colorectal neoplasia

Diseases of the Colon & Rectum, 1995

This study was designed to determine whether patients with coronary artery disease are at elevate... more This study was designed to determine whether patients with coronary artery disease are at elevated risk for colorectal neoplasia. A case-control study was conducted among consecutive patients in three colonoscopy practices in New York City from 1986 to 1988. All study participants completed an interview questionnaire covering demographics, diet, environmental and behavioral exposures, family and personal medical history, and other variables. For the present study, 298 newly diagnosed colorectal adenoma cases and 107 incident cancer cases were compared with 507 colonoscoped controls without colorectal neoplasia or other significant findings on colonoscopy. Data on history of coronary artery disease (angina and/or heart attack) were obtained solely from the study participants' questionnaire responses. No association was observed between angina, heart attack, or either and colorectal adenomas in males. However, prior coronary artery disease was found to be associated with colorectal cancer in males more than 60 years of age and with colorectal adenomas in females aged 50 years or younger. Men with coronary artery disease may be at elevated risk for subsequent colorectal cancer. Young women with coronary artery disease also may be at elevated risk for colorectal neoplasia.

Research paper thumbnail of Evaluation of 4-aminobiphenyl-DNA adducts in human breast cancer: the influence of tobacco smoke

Carcinogenesis, 2003

Breast cancer is one of the major cancers around the world but its etiology is still not well und... more Breast cancer is one of the major cancers around the world but its etiology is still not well understood. Only~50% of the disease is associated with known risk factors including highly penetrant genes and lifestyle factors. Thus, environmental carcinogens may play an important role in the etiology of breast cancer. The arylamine 4-aminobiphenyl (4-ABP) is a tobacco smoke constituent, an environmental contaminant, and a well-established bladder carcinogen in rodents and humans. In this study, we investigated the role of 4-ABP in the etiology of human breast cancer by measuring 4-ABP±DNA adducts using a monoclonal antibody based immunoperoxidase method that had been validated by comparison with gas chromatography/mass spectroscopy analysis of liver tissues from 4-ABP-treated mice. Adducts were analyzed in 150 paraffin-embedded breast tumors and in 55 adjacent normal tissues collected from cases in the Long Island Breast Cancer Study Project. The role of polymorphisms in genes involved in the metabolism of 4-ABP including N-acetyl transferase 2 (NAT2), cytochrome P4501A2 (CYP1A2) and glutathione S-transferase M1 (GSTM1) and the nucleotide excision repair gene XPD was also explored in the same patients. The mean logtransformed relative staining intensity for 4-ABP±DNA adducts was higher in normal (5.93 AE 0.54) than in the corresponding tumor (5.44 AE 0.62, P 5 0.0001) tissues. However, a highly significant positive correlation was observed between the levels of 4-ABP±DNA in both tissues (r 0.72, P 5 0.0001). Smoking status was correlated with the levels of 4-ABP±DNA in tumor adjacent normal tissues with a significant linear trend (P 0.04) for current, former and never smokers; adducts were not related to smoking status in tumor tissues. No correlation was observed between the levels of 4-ABP±DNA and polymorphisms in the genes analyzed even when subjects were stratified by smoking status. These results demonstrate that smoking is associated with increased levels of 4-ABP±DNA adducts in human mammary tissue. In this study, genetic polymorphisms did not significantly affect the formation of 4-ABP±DNA adducts in breast cancer cases, perhaps due to the small number of samples.

Research paper thumbnail of Levels of p53 antigen in the plasma of patients with adenomas and carcinomas of the colon

Cancer Letters, 1995

Plasma levels of p53 protein were examined by an enzyme linked immunosorbent assay in 184 patient... more Plasma levels of p53 protein were examined by an enzyme linked immunosorbent assay in 184 patients enrolled in a colonoscopy study. The mean levels among 47 individuals with normal colonoscopic examinations and no prior history of colonic neoplasia (0.12 ng/ml) and among 61 individuals with normal colonoscopic examinations and a prior history of colonic neoplasia (0.09 ng/ml) were similar. However, the mean levels among 54 individuals with newly diagnosed colonic adenomas (0.44 ng/ml) and 22 individuals with newly diagnosed colonic carcinomas (0.55 ng/ml) were statistically significantly elevated compared to the normal controls (P < 0.02). Among these tumor patients, the plasma levels tended to increase with increasing adenoma size and with increasing carcinoma stage, although these trends were not statistically significant. Defining a significant positive plasma level as any value greater than ten times background, the percentage of positive samples increased from 4% in the controls to 20% in the adenoma cases to 32% in the carcinoma cases. These results demonstrate that plasma p53 protein levels are elevated in a subgroup of individuals with colonic neoplasia.

Research paper thumbnail of Reproductive risk factors for colorectal adenomatous polyps (New York City, NY, United States)

Cancer Causes and Control, 1995

Events of reproductive life, such as parity and age at menarche, have been found in some but not ... more Events of reproductive life, such as parity and age at menarche, have been found in some but not all studies to be associated with risk for colorectal cancer in females. Because adenomatous polyps (adenomas) are precursors of colorectal cancer, we investigated whether reproductive variables were associated with colorectal adenomas. We conducted a case-control study among patients examined in three colonoscopy practices in New York City (NY, United States) from 1986 to 1988. Adenoma cases (n = 128) were defined as women who had an adenoma detected at the index colonoscopy with no history of inflammatory bowel disease, adenomas, or cancer. Controls (n = 283) were women with a normal index colonoscopy and no history of inflammatory bowel disease, adenomas, or cancer. The adjusted odds ratio (OR) for the association of early menarche (age less than 13 years) with adenomas was 0.6 (95 percent confidence interval = 0.4-0.9). Parity, history of spontaneous or induced abortion, infertility, type of menopause, age at menopause, use of oral contraceptives, and use of menopausal hormone replacement therapy were not associated statistically significantly with adenoma risk, although some possible trends were observed. Our findings do not implicate reproductive events, nulliparity, or overexposure to estrogens or to menstrual cycles as mechanisms of increased risk for colorectal neoplasia. Cancer Causes and Control 1995, 6, 513-518

Research paper thumbnail of Cigarette smoking and other behavioral risk factors for recurrence of colorectal adenomatous polyps (New York City, NY, USA)

Cancer Causes & Control, 1994

Adenomatous polyps (hereinafter referred to as adenomas) are known precursors of colorectal cance... more Adenomatous polyps (hereinafter referred to as adenomas) are known precursors of colorectal cancer. Cigarette smoking has been associated with adenomas but not with colorectal cancer, while alcohol and fat intake have been associated with both adenomas and cancer in some studies. Approximately 30 percent of patients with resected adenomas develop another adenoma within three years. This case-control study explores the association of cigarette smoking with adenoma recurrence. Between April 1986 and March 1988, we administered a questionnaire to colonoscoped patients aged 35 to 84 years in three New York City (NY, USA) practices. We compared 186 recurrent polyp cases (130 males, 56 females) and 330 controls (187 males, 143 females) who had a history of polypectomy but normal follow-up colonoscopy, by cigarette-smoking pack-years adjusted for possible confounders. Risk for a metachronous or recurrent adenoma was significantly greater in the highest quartile of smokers than in never-smokers among both men (odds ratio [OR] = 1.8, 95 percent confidence interval [CI] --1.0-3.4) and women (OR = 3.6, CI = 1.7-7.6). Adjustment for time since smoking cessation reduced risk only slightly, as did adjustment for dietary fat intake, which itself remained significant. No association was found between alcohol intake and risk of recurrence. Cigarette smokers appear to have an elevated risk of adenoma recurrence that is not eliminated entirely by smoking cessation. Intervention trials that use adenoma recurrence as an endpoint should take smoking into account.

Research paper thumbnail of Relationship between breast cancer and colorectal adenomatous polyps a case-control study

Cancer, 1992

Although there is a known reciprocal association between breast and colorectal cancer in women, f... more Although there is a known reciprocal association between breast and colorectal cancer in women, few studies have investigated whether a similar association exists between breast cancer and colorectal adenomatous polyps, known to be precursor lesions for colon cancer. A case-control study was conducted on patients in three colonoscopy practices in New York to determine possible risk factors for adenomatous polyps. Among women studied, there were 128 patients with incident adenomatous polyps and 284 control subjects who underwent colonoscopy and had no colorectal neoplasia. No significant association between the incidence of an adenomatous polyp in the colon or rectum and a history of breast cancer was found (odds ratio, 0.71; 95% confidence interval, 0.34 to 1.64). If shared risk factors for breast and colorectal cancer are the reasons for the concurrence of these two malignant lesions, these results suggest that these factors act at the level of promoting adenomatous polyps of the colon and rectum into colorectal cancer.

Research paper thumbnail of The effect of calcium and vitamin supplements on the incidence and recurrence of colorectal adenomatous polyps

Research paper thumbnail of Cholecystectomy as a risk factor for colorectal adenomatous polyps and carcinoma

Cancer, 1991

Multiple studies have suggested a possible relationship between prior cholecystectomy and the occ... more Multiple studies have suggested a possible relationship between prior cholecystectomy and the occurrence of subsequent colorectal carcinoma. This relationship has been particularly noticed among female patients and for right-sided lesions of the colon. In the current study, the authors undertook a case-control study among patients who underwent colonoscopy in three private practices in New York City between April 1986 and March 1988. Over this period, 302 adenomatous polyp cases, 106 colon cancer cases, and 507 controls were interviewed regarding their prior history of cholecystectomy. Overall, no significant association was observed between cholecystectomy and either colorectal adenomatous polyps or cancer. Cholecystectomy does not appear to be a significant risk factor for colorectal neoplasia.

Research paper thumbnail of The Long Island Breast Cancer Study Project: Description of a Multi-Institutional Collaboration to Identify Environmental Risk Factors for Breast Cancer

Breast Cancer Research and Treatment, 2002

The metabolism of the estrogenic hormone is oxidative in nature in contrast to the reductive path... more The metabolism of the estrogenic hormone is oxidative in nature in contrast to the reductive pathway for the neutral steroid hormones.

Research paper thumbnail of Prognostic significance of gene-specific promoter hypermethylation in breast cancer patients

Breast Cancer Research and Treatment, 2012

The association between promoter methylation status and survival was investigated in a large coho... more The association between promoter methylation status and survival was investigated in a large cohort of women with breast cancer, participants in the Long Island Breast Cancer Study Project. Archived tumor tissues (n = 839) were collected from women diagnosed with a first primary invasive or in situ breast cancer in 1996-1997. Vital status was followed through the end of 2005 with a mean follow-up time of 8 years. Promoter methylation of eight breast cancer-related genes was assessed by Methy-Light. The frequencies of methylation for HIN1, RASSF1A, DAPK1, GSTP1, CyclinD2, TWIST, CDH1 and RARb were 62.9, 85.2, 14.1, 27.8, 19.6, 15.3, 5.8 and 27.6%, respectively. Since survival rates of in situ and invasive breast cancers are substantially different, survival analyses were conducted within 670 invasive cases with complete data on all genes. Age-adjusted Cox proportional hazards models revealed that GSTP1, TWIST and RARb methylation was significantly associated with higher breast cancer-specific mortality. Methylation of GSTP1 and RARb was significantly associated with higher all-cause mortality. To investigate the relationship between the number of methylated genes and breast cancer-specific mortality, we included previously published MethyLight data on p16 and APC methylation status. Breast cancer-specific mortality increased in a dose-dependent manner with increasing number of methylated genes (P trend = 0.002), although confidence intervals were wide. Our results suggest that promoter methylation, particularly for a panel of genes, has the potential to be used as a biomarker for predicting prognosis in breast cancer.

Research paper thumbnail of Gene promoter methylation is associated with increased mortality among women with breast cancer

Breast Cancer Research and Treatment, 2010

To better understand breast cancer etiology and progression, we explored the association between ... more To better understand breast cancer etiology and progression, we explored the association between promoter methylation status of three breast cancer related genes (BRCA1, APC and p16) and survival in a large cohort of women with breast cancer. About 800 archived tumor tissues were collected from women diagnosed with a first primary invasive or in situ breast cancer in 1996-1997. The vital status of the participants was followed through the end of year 2005 with a mean follow up time of 8.0 years. Promoter methylation was assessed by methylation-specific PCR (for BRCA1) and MethyLight (for APC and p16). The association of promoter methylation and breast cancer mortality was evaluated by Cox-proportional hazards models. Methylated promoters were found in 59.0%, 48.4% and 3.6% of the tumor samples for BRCA1, APC and p16, respectively. Breast cancer-specific mortality was strongly associated with promoter methylation of p16 [HR and 95% CI: 3.53(1.83-6.78)], whereas the associations with of BRCA1 and APC were less pronounced [HR and 95% CI: 1.81(1.18-2.78) and 1.46(0.98-2.17), respectively]. Similar associations were observed with allcause mortality. As the number of methylated genes increased, the risk of breast cancer-specific mortality also increased in a dose-dependent manner (p, trend=0.01). Importantly, even with our results stratified by hormone receptor status, promoter methylation of the three genes remained predictive of mortality. Our results suggest that promoter methylation could be promising epigenetic markers to be considered for breast cancer survival.