The Metabolic Syndrome (MetSyn), which is a clustering of traits including insulin resistance, ob... more The Metabolic Syndrome (MetSyn), which is a clustering of traits including insulin resistance, obesity, hypertension and dyslipidemia, is estimated to have a substantial genetic component, yet few specific genetic targets have been identified. Factor analysis, a sub-type of structural equation modeling (SEM), has been used to model the complex relationships in MetSyn. Therefore, we aimed to define the genetic determinants of MetSyn in the Framingham Heart Study (Offspring Cohort, Exam 7) using the Affymetrix 50 k Human Gene Panel and three different approaches: 1) an association-based "one-SNP-at-a-time" analysis with MetSyn as a binary trait using the World Health Organization criteria; 2) an association-based "one-SNP-at-a-time" analysis with MetSyn as a continuous trait using second-order factor scores derived from four first-order factors; and, 3) a multivariate SEM analysis with MetSyn as a continuous, second-order factor modeled with multiple putative genes...
Insulin resistance (IR) is postulated to underlie diabetes, the metabolic syndrome (MS) and cardi... more Insulin resistance (IR) is postulated to underlie diabetes, the metabolic syndrome (MS) and cardiovascular disease (CVD). The D20S32e marker close to the melanocortin receptor-3 (hMC3-R) has been shown to be associated with IR in a large New Zealand Māori kindred, a population at high risk for MS and CVD. Here we examine the potential association of the D20S32e marker with the MS in this 60 member Māori kindred. There was a significant association between the D20S32e "B" allele and the fasting insulin component under both polygenic (beta=-5.3077; p=0.008) and common sibship effect (beta=-4.2161; p=0.03) models. No significant association between the same allele of D20S32e and the MS was observed after adjusting for age under a polygenic (p=0.103) or sibling (p=0.09) correlation model. We conclude that in this Māori kindred, the D20S32e polymorphism is significantly associated with insulin resistance but not with MS. Our data supports the hypothesis that multiple gene varia...
To date, the potential impact of hormones on prostate cancer has predominantly focused on recepto... more To date, the potential impact of hormones on prostate cancer has predominantly focused on receptor-mediated events. However, catechol estrogens, if not inactivated by catechol-O-methyltransferase (COMT), can generate large quantities of reactive oxygen species (ROS). ROS may cause a spectrum of damage including oxidative DNA base lesions, which can lead to irreversible mutation(s) if they are not repaired by base excision repair (BER) systems. hOGG1 is a key enzyme in short patch BER because it recognizes and performs initial excision of the most common form of oxidative DNA base damage, 8-hydroxyguanine (8-oxo-dG). To investigate potential non-receptor-mediated estrogen effects, we evaluated the association between COMT Val158Met and hOGG1 Ser326Cys polymorphisms and prostate cancer in a family-based case-control study (439 prostate cancer cases, 479 brother controls). We observed no noteworthy associations between these polymorphisms and prostate cancer risk in the total study pop...
Obesity has been associated with increased colon cancer risk in epidemiological studies; however,... more Obesity has been associated with increased colon cancer risk in epidemiological studies; however, the specific time periods during which obesity may be most relevant as well as how changes in adult body size over time affect colon cancer risk have not been well explored. We evaluated potential associations between BMI in each age decade(20s, 30s, 40s, 50s, and 2 years before study recruitment ("recruitment period")) and in BMI changes over timeand colon cancer risk in a population-based case-control study comprising 438 cases and 491 controls. We found that obese (BMI>or=30.0 kg/m2) compared to normal (BMI>or=18.5 to <25.0 kg/m2) body size at the recruitment period was associated with increased colon cancer risk (odds ratio (OR)=1.54; 95% confidence interval (CI)=1.03-2.31; P=0.03). No associations were observed for obese body size in the other age decades. An increased risk was found for changes in BMI between the 30s decade and the recruitment period of 5-10 kg/m2 (OR=1.54; 95%CI=1.02-2.34; P=0.04) and >10 kg/m2 (OR=2.40; 95% CI=1.23-4.66; P=0.01) (P trend=0.01). Stratification by gender revealed that BMI changes>10 kg/m2 increased risk in women but not men. Similar results were found for BMI changes between the 20s decade and the recruitment period but effect sizes were smaller. Our results provide additional support to obesity's role in colon cancer and suggest large body size increases exceeding 10 kg/m2 may potentially be more important after age 30, particularly among women; however, prospective studies with sex hormone, growth factor, and pro-inflammatory biomarkers are needed to provide insights to the underlying biological mechanism(s).
Journal of physical therapy and health promotion, 2013
African-American (AA) women have higher rates of breast cancer (BCa) mortality than Caucasian wom... more African-American (AA) women have higher rates of breast cancer (BCa) mortality than Caucasian women, and a recent study using data from the Surveillance, Epidemiology and End Results (SEER) registry suggests that this disparity may be due, in part, to the poorer health status of AAs at diagnosis and not treatment related issues. Randomized controlled trials involving supervised aerobic and resistance exercise have shown improved body composition and improvement in cancer-related biomarkers in BCa patients and may lead to improved recurrence and survival rates; however, most trials have focused on Caucasians and many have been conducted in academic- and clinic-based settings. We evaluated the feasibility of conducting a 20-week, supervised, resistance training, group exercise intervention coupled with a support group and home walking program utilizing facilities and personnel at a community cancer support center (The Gathering Place, Beachwood, Ohio) in AA Stage I-III BCa survivors w...
Physical activity has been shown to be inversely associated with breast cancer recurrence and sur... more Physical activity has been shown to be inversely associated with breast cancer recurrence and survival. Although physical activity is known to decline with age, rates of change in physical activity have not been well characterized in breast cancer patients and subgroups with known disparities in breast cancer survival, especially in minorities, the elderly, and the obese. We evaluated moderate and strenuous physical activity from high school through diagnosis in 1,220 breast cancer patients, and from high school to recruitment in 935 controls. We compared the proportion of patients and controls meeting the American Cancer Society (ACS) guidelines for physical activity and differences in declines in level of physical activity by race, age, and obesity. At diagnosis, only 33.2% of breast cancer patients met the ACS physical activity guidelines. Only 13.2, 24.7, and 30.5% of African-American (AA), obese, and older (≥65 years) patients met the guidelines, respectively. Controls showed s...
Obesity has been associated with increased colon cancer risk in epidemiological studies; however,... more Obesity has been associated with increased colon cancer risk in epidemiological studies; however, the specific time periods during which obesity may be most relevant as well as how changes in adult body size over time affect colon cancer risk have not been well explored. We evaluated potential associations between BMI in each age decade(20s, 30s, 40s, 50s, and 2 years before study recruitment ("recruitment period")) and in BMI changes over timeand colon cancer risk in a population-based case-control study comprising 438 cases and 491 controls. We found that obese (BMI>or=30.0 kg/m2) compared to normal (BMI>or=18.5 to <25.0 kg/m2) body size at the recruitment period was associated with increased colon cancer risk (odds ratio (OR)=1.54; 95% confidence interval (CI)=1.03-2.31; P=0.03). No associations were observed for obese body size in the other age decades. An increased risk was found for changes in BMI between the 30s decade and the recruitment period of 5-10 kg/m2 (OR=1.54; 95%CI=1.02-2.34; P=0.04) and >10 kg/m2 (OR=2.40; 95% CI=1.23-4.66; P=0.01) (P trend=0.01). Stratification by gender revealed that BMI changes>10 kg/m2 increased risk in women but not men. Similar results were found for BMI changes between the 20s decade and the recruitment period but effect sizes were smaller. Our results provide additional support to obesity's role in colon cancer and suggest large body size increases exceeding 10 kg/m2 may potentially be more important after age 30, particularly among women; however, prospective studies with sex hormone, growth factor, and pro-inflammatory biomarkers are needed to provide insights to the underlying biological mechanism(s).
The Metabolic Syndrome (MetSyn), which is a clustering of traits including insulin resistance, ob... more The Metabolic Syndrome (MetSyn), which is a clustering of traits including insulin resistance, obesity, hypertension and dyslipidemia, is estimated to have a substantial genetic component, yet few specific genetic targets have been identified. Factor analysis, a sub-type of structural equation modeling (SEM), has been used to model the complex relationships in MetSyn. Therefore, we aimed to define the genetic determinants of MetSyn in the Framingham Heart Study (Offspring Cohort, Exam 7) using the Affymetrix 50 k Human Gene Panel and three different approaches: 1) an association-based "one-SNP-at-a-time" analysis with MetSyn as a binary trait using the World Health Organization criteria; 2) an association-based "one-SNP-at-a-time" analysis with MetSyn as a continuous trait using second-order factor scores derived from four first-order factors; and, 3) a multivariate SEM analysis with MetSyn as a continuous, second-order factor modeled with multiple putative genes...
Insulin resistance (IR) is postulated to underlie diabetes, the metabolic syndrome (MS) and cardi... more Insulin resistance (IR) is postulated to underlie diabetes, the metabolic syndrome (MS) and cardiovascular disease (CVD). The D20S32e marker close to the melanocortin receptor-3 (hMC3-R) has been shown to be associated with IR in a large New Zealand Māori kindred, a population at high risk for MS and CVD. Here we examine the potential association of the D20S32e marker with the MS in this 60 member Māori kindred. There was a significant association between the D20S32e "B" allele and the fasting insulin component under both polygenic (beta=-5.3077; p=0.008) and common sibship effect (beta=-4.2161; p=0.03) models. No significant association between the same allele of D20S32e and the MS was observed after adjusting for age under a polygenic (p=0.103) or sibling (p=0.09) correlation model. We conclude that in this Māori kindred, the D20S32e polymorphism is significantly associated with insulin resistance but not with MS. Our data supports the hypothesis that multiple gene varia...
To date, the potential impact of hormones on prostate cancer has predominantly focused on recepto... more To date, the potential impact of hormones on prostate cancer has predominantly focused on receptor-mediated events. However, catechol estrogens, if not inactivated by catechol-O-methyltransferase (COMT), can generate large quantities of reactive oxygen species (ROS). ROS may cause a spectrum of damage including oxidative DNA base lesions, which can lead to irreversible mutation(s) if they are not repaired by base excision repair (BER) systems. hOGG1 is a key enzyme in short patch BER because it recognizes and performs initial excision of the most common form of oxidative DNA base damage, 8-hydroxyguanine (8-oxo-dG). To investigate potential non-receptor-mediated estrogen effects, we evaluated the association between COMT Val158Met and hOGG1 Ser326Cys polymorphisms and prostate cancer in a family-based case-control study (439 prostate cancer cases, 479 brother controls). We observed no noteworthy associations between these polymorphisms and prostate cancer risk in the total study pop...
Obesity has been associated with increased colon cancer risk in epidemiological studies; however,... more Obesity has been associated with increased colon cancer risk in epidemiological studies; however, the specific time periods during which obesity may be most relevant as well as how changes in adult body size over time affect colon cancer risk have not been well explored. We evaluated potential associations between BMI in each age decade(20s, 30s, 40s, 50s, and 2 years before study recruitment ("recruitment period")) and in BMI changes over timeand colon cancer risk in a population-based case-control study comprising 438 cases and 491 controls. We found that obese (BMI>or=30.0 kg/m2) compared to normal (BMI>or=18.5 to <25.0 kg/m2) body size at the recruitment period was associated with increased colon cancer risk (odds ratio (OR)=1.54; 95% confidence interval (CI)=1.03-2.31; P=0.03). No associations were observed for obese body size in the other age decades. An increased risk was found for changes in BMI between the 30s decade and the recruitment period of 5-10 kg/m2 (OR=1.54; 95%CI=1.02-2.34; P=0.04) and >10 kg/m2 (OR=2.40; 95% CI=1.23-4.66; P=0.01) (P trend=0.01). Stratification by gender revealed that BMI changes>10 kg/m2 increased risk in women but not men. Similar results were found for BMI changes between the 20s decade and the recruitment period but effect sizes were smaller. Our results provide additional support to obesity's role in colon cancer and suggest large body size increases exceeding 10 kg/m2 may potentially be more important after age 30, particularly among women; however, prospective studies with sex hormone, growth factor, and pro-inflammatory biomarkers are needed to provide insights to the underlying biological mechanism(s).
Journal of physical therapy and health promotion, 2013
African-American (AA) women have higher rates of breast cancer (BCa) mortality than Caucasian wom... more African-American (AA) women have higher rates of breast cancer (BCa) mortality than Caucasian women, and a recent study using data from the Surveillance, Epidemiology and End Results (SEER) registry suggests that this disparity may be due, in part, to the poorer health status of AAs at diagnosis and not treatment related issues. Randomized controlled trials involving supervised aerobic and resistance exercise have shown improved body composition and improvement in cancer-related biomarkers in BCa patients and may lead to improved recurrence and survival rates; however, most trials have focused on Caucasians and many have been conducted in academic- and clinic-based settings. We evaluated the feasibility of conducting a 20-week, supervised, resistance training, group exercise intervention coupled with a support group and home walking program utilizing facilities and personnel at a community cancer support center (The Gathering Place, Beachwood, Ohio) in AA Stage I-III BCa survivors w...
Physical activity has been shown to be inversely associated with breast cancer recurrence and sur... more Physical activity has been shown to be inversely associated with breast cancer recurrence and survival. Although physical activity is known to decline with age, rates of change in physical activity have not been well characterized in breast cancer patients and subgroups with known disparities in breast cancer survival, especially in minorities, the elderly, and the obese. We evaluated moderate and strenuous physical activity from high school through diagnosis in 1,220 breast cancer patients, and from high school to recruitment in 935 controls. We compared the proportion of patients and controls meeting the American Cancer Society (ACS) guidelines for physical activity and differences in declines in level of physical activity by race, age, and obesity. At diagnosis, only 33.2% of breast cancer patients met the ACS physical activity guidelines. Only 13.2, 24.7, and 30.5% of African-American (AA), obese, and older (≥65 years) patients met the guidelines, respectively. Controls showed s...
Obesity has been associated with increased colon cancer risk in epidemiological studies; however,... more Obesity has been associated with increased colon cancer risk in epidemiological studies; however, the specific time periods during which obesity may be most relevant as well as how changes in adult body size over time affect colon cancer risk have not been well explored. We evaluated potential associations between BMI in each age decade(20s, 30s, 40s, 50s, and 2 years before study recruitment ("recruitment period")) and in BMI changes over timeand colon cancer risk in a population-based case-control study comprising 438 cases and 491 controls. We found that obese (BMI>or=30.0 kg/m2) compared to normal (BMI>or=18.5 to <25.0 kg/m2) body size at the recruitment period was associated with increased colon cancer risk (odds ratio (OR)=1.54; 95% confidence interval (CI)=1.03-2.31; P=0.03). No associations were observed for obese body size in the other age decades. An increased risk was found for changes in BMI between the 30s decade and the recruitment period of 5-10 kg/m2 (OR=1.54; 95%CI=1.02-2.34; P=0.04) and >10 kg/m2 (OR=2.40; 95% CI=1.23-4.66; P=0.01) (P trend=0.01). Stratification by gender revealed that BMI changes>10 kg/m2 increased risk in women but not men. Similar results were found for BMI changes between the 20s decade and the recruitment period but effect sizes were smaller. Our results provide additional support to obesity's role in colon cancer and suggest large body size increases exceeding 10 kg/m2 may potentially be more important after age 30, particularly among women; however, prospective studies with sex hormone, growth factor, and pro-inflammatory biomarkers are needed to provide insights to the underlying biological mechanism(s).
Uploads
Papers by Nora Nock