Physical Activity / Exercise
Lifestyle influence/damage P53 gene (tumor suppressor)
>16 February 2010
New research sheds light on breast cancer prognosis for poorer women
Researchers from the University of Dundee have established a link between deprivation and the p53 gene that explains why women from poorer backgrounds are less likely to survive breast cancer.
In a paper published in this month’s British Journal of Cancer, the Dundee team identifies – for the first time – that p53 mutation in breast cancer is associated with socio-economic deprivation, and that this helps account for the poorer prognosis for women from deprived communities.
Deprivation has long been known to play a role in the development of a wide range of diseases and to a higher risk of recurrence or death for patients diagnosed with a number of cancers, including breast cancer.
The reasons for survival rates differing between breast cancer sufferers from poorer areas and from more affluent areas – the deprivation gap – has never been fully understood.
Initiating this study, Dr Lee Baker, of the Department of Surgery and Molecular Oncology, suggested examining the p53 gene as a candidate molecular marker that might account for these biological differences.
What the team found was that women from deprived backgrounds were more likely to experience a mutation of p53, and that this linked to higher relapse and mortality rates.
‘There are two ways that p53 mutations can come about,’ explained Dr Baker. ‘One is as a result of genetic predisposition, and the other is as a result of lifestyle.
Smoking, drinking, poor diet etc can lead to p53 mutations and are more common in women from lower socio-economic groups, who are also more likely to experience a recurrence of the disease and to die as a result of breast cancer.’
‘This research makes a strong link between p53 and deprivation, and then between p53 mutation and recurrence and death. As a social issue, it shows that if we lift people up the deprivation scale then they will be less likely to have problems with their p53 gene, and go on to develop breast cancer.’
‘In terms of science, it shows that successfully creating a treatment for p53 mutation will go a long way down the road to finding a cure for this form of breast cancer.
Deprivation alone doesn’t cause breast cancer, but can affect prognosis when p53 is damaged as a result of lifestyle choices commonly associated with deprivation.’
p53 is a tumor suppressor protein that is involved in preventing cancer. In healthy humans, the p53 protein is continually produced and degraded in the cell but if the gene becomes damaged, or mutates, then tumor suppression is severely reduced.
The survey looked at a total of 246 women who underwent treatment for breast cancer between 1997 and 2001. Examining frozen tissue, tests were carried out to determine p53 mutation status. Using the patients’ postcodes, a deprivation score was attributed to each, and examined against the outcome (full recovery, relapse, death etc).
What the team found was that patients in the lowest socio-economic group were significantly more likely to have a relapse and die compared to those in more affluent categories. They also demonstrated that the worse survival and shorter disease-free interval in breast cancer for the most deprived patients is associated with tumour p53 mutation.
The research combines the skill sets of several different disciplines and is an example of the unique combination of clinical data, statistical data and high-quality molecular biology laboratory analyses that Dundee is developing. It also featured collaborative working between the University and Roche Diagnostics, a US-based diagnostic company, who developed for this study a novel technology to determine quickly and reliably p53 mutation in tumours.
Alastair Thompson, professor of Surgical Oncology at the University, explained the significance of the research.
‘Although the data will in future need confirmation in additional studies, this paper suggests, for the first time, an underlying biology, based around the p53 gene, explaining why women with breast cancer from the most deprived backgrounds do worst in terms of survival,’ he said.
‘We would like to explore this further with collaborating colleagues in Europe. Our partners Roche Diagnostics produce a test that allows the detection of p53 mutations and that was particularly useful in this context.’
Professor Thompson expressed gratitude to all those who helped fund the study, including the patients, Breast Cancer Research Scotland and the Tayside Tissue Bank, which provided samples and was established with finance from Cancer Research UK and the Medical Research Council.
Ann’s NOTE: It is interesting that there is NO mention of stress. Stress which might consist of worry about feeding oneself, ones’ children, rushing to a job, being treated ‘badly’ on the job, rudeness, etc.
About the British Journal of Cancer (BJC)
The BJC is owned by Cancer Research UK. Its mission is to encourage communication of the very best cancer research from laboratories and clinics in all countries. Broad coverage, its editorial independence and consistent high standards have made BJC one of the world’s premier general cancer journals.
www.bjcancer.com.
>16 February 2010
New research sheds light on breast cancer prognosis for poorer women
Researchers from the University of Dundee have established a link between deprivation and the p53 gene that explains why women from poorer backgrounds are less likely to survive breast cancer.
In a paper published in this month’s British Journal of Cancer, the Dundee team identifies – for the first time – that p53 mutation in breast cancer is associated with socio-economic deprivation, and that this helps account for the poorer prognosis for women from deprived communities.
Deprivation has long been known to play a role in the development of a wide range of diseases and to a higher risk of recurrence or death for patients diagnosed with a number of cancers, including breast cancer.
The reasons for survival rates differing between breast cancer sufferers from poorer areas and from more affluent areas – the deprivation gap – has never been fully understood.
Initiating this study, Dr Lee Baker, of the Department of Surgery and Molecular Oncology, suggested examining the p53 gene as a candidate molecular marker that might account for these biological differences.
What the team found was that women from deprived backgrounds were more likely to experience a mutation of p53, and that this linked to higher relapse and mortality rates.
‘There are two ways that p53 mutations can come about,’ explained Dr Baker. ‘One is as a result of genetic predisposition, and the other is as a result of lifestyle.
Smoking, drinking, poor diet etc can lead to p53 mutations and are more common in women from lower socio-economic groups, who are also more likely to experience a recurrence of the disease and to die as a result of breast cancer.’
‘This research makes a strong link between p53 and deprivation, and then between p53 mutation and recurrence and death. As a social issue, it shows that if we lift people up the deprivation scale then they will be less likely to have problems with their p53 gene, and go on to develop breast cancer.’
‘In terms of science, it shows that successfully creating a treatment for p53 mutation will go a long way down the road to finding a cure for this form of breast cancer.
Deprivation alone doesn’t cause breast cancer, but can affect prognosis when p53 is damaged as a result of lifestyle choices commonly associated with deprivation.’
p53 is a tumor suppressor protein that is involved in preventing cancer. In healthy humans, the p53 protein is continually produced and degraded in the cell but if the gene becomes damaged, or mutates, then tumor suppression is severely reduced.
The survey looked at a total of 246 women who underwent treatment for breast cancer between 1997 and 2001. Examining frozen tissue, tests were carried out to determine p53 mutation status. Using the patients’ postcodes, a deprivation score was attributed to each, and examined against the outcome (full recovery, relapse, death etc).
What the team found was that patients in the lowest socio-economic group were significantly more likely to have a relapse and die compared to those in more affluent categories. They also demonstrated that the worse survival and shorter disease-free interval in breast cancer for the most deprived patients is associated with tumour p53 mutation.
The research combines the skill sets of several different disciplines and is an example of the unique combination of clinical data, statistical data and high-quality molecular biology laboratory analyses that Dundee is developing. It also featured collaborative working between the University and Roche Diagnostics, a US-based diagnostic company, who developed for this study a novel technology to determine quickly and reliably p53 mutation in tumours.
Alastair Thompson, professor of Surgical Oncology at the University, explained the significance of the research.
‘Although the data will in future need confirmation in additional studies, this paper suggests, for the first time, an underlying biology, based around the p53 gene, explaining why women with breast cancer from the most deprived backgrounds do worst in terms of survival,’ he said.
‘We would like to explore this further with collaborating colleagues in Europe. Our partners Roche Diagnostics produce a test that allows the detection of p53 mutations and that was particularly useful in this context.’
Professor Thompson expressed gratitude to all those who helped fund the study, including the patients, Breast Cancer Research Scotland and the Tayside Tissue Bank, which provided samples and was established with finance from Cancer Research UK and the Medical Research Council.
Ann’s NOTE: It is interesting that there is NO mention of stress. Stress which might consist of worry about feeding oneself, ones’ children, rushing to a job, being treated ‘badly’ on the job, rudeness, etc.
About the British Journal of Cancer (BJC)
The BJC is owned by Cancer Research UK. Its mission is to encourage communication of the very best cancer research from laboratories and clinics in all countries. Broad coverage, its editorial independence and consistent high standards have made BJC one of the world’s premier general cancer journals.
www.bjcancer.com.
Lifetime physical activity and the risk of renal cell cancer
Epidemiology
Lifetime physical activity and the risk of renal cell cancer
Alessandra Tavani 1 *, Antonella Zucchetto 2, Luigino Dal Maso 2, Maurizio Montella 3, Valerio Ramazzotti 4, Renato Talamini 2, Silvia Franceschi 5, Carlo La Vecchia 1 6
email: Alessandra Tavani ([email protected])
*Correspondence to Alessandra Tavani, Istituto di Ricerche Farmacologiche Mario Negri, Via Eritrea 62, 20157 Milano, Italy
Fax: +39-02-3900-1916.
Funded by:
Italian Association for Cancer Research
Italian League against Cancer
Italian Ministry of Education; Grant Number: PRIN 2005
Abstract
The relation between lifelong physical activity at work and during leisure-time and the risk of renal cell cancer (RCC) was analyzed in a case-control study conducted in Italy between 1992 and 2004. Cases were 767 subjects with incident, histologically confirmed RCC, and controls were 1,534 patients hospitalized for acute nonneoplastic conditions.
Odds ratios (OR) and 95% confidence intervals (CI) for RCC were computed by multiple logistic regression models, conditioned on study center, sex and age, and adjusted for main covariates. Compared to the lowest level of occupational physical activity, the multivariate OR of RCC for the highest level were 0.65 (95% CI 0.49-0.87) at age 12 years, 0.67 (95% CI 0.53-0.84) at age 15-19, 0.74 (95% CI 0.59-0.93) at age 30-39 and 0.71 (95% CI 0.55-0.92) at age 50-59 years, with significant inverse trends in risk.
The inverse association was consistent in strata of sex, age at diagnosis, body mass index, smoking habit and alcohol drinking. No significant association was found for leisure-time physical activity. The inverse association between occupational physical activity and RCC risk, if real, may be related to the effects of insulin-like growth factors, or lipid peroxidation and about 9% of cases of RCC in Italy could be avoided by increasing physical activity.
However the inverse association might involve confounding by indirect mechanisms, such as body composition or other social class correlates.
International Journal of Cancer
Volume 120, Issue 9 , Pages 1977 – 1980
Epidemiology
Lifetime physical activity and the risk of renal cell cancer
Alessandra Tavani 1 *, Antonella Zucchetto 2, Luigino Dal Maso 2, Maurizio Montella 3, Valerio Ramazzotti 4, Renato Talamini 2, Silvia Franceschi 5, Carlo La Vecchia 1 6
- Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy
- Unitá di Epidemiologia e Biostatistica, Centro di Riferimento Oncologico, Aviano (PN), Italy
- Servizio di Epidemiologia, Istituto Tumori Fondazione Pascale, Naples, Italy
- Servizio Integrato di Epidemiologia e Sistemi Informativi, Istituto Nazionale Tumori Regina Elena, Rome, Italy
- International Agency for Research on Cancer, Lyon, France
- Istituto di Statistica Medica e Biometria, Università degli Studi di Milano, Milan, Italy
email: Alessandra Tavani ([email protected])
*Correspondence to Alessandra Tavani, Istituto di Ricerche Farmacologiche Mario Negri, Via Eritrea 62, 20157 Milano, Italy
Fax: +39-02-3900-1916.
Funded by:
Italian Association for Cancer Research
Italian League against Cancer
Italian Ministry of Education; Grant Number: PRIN 2005
Abstract
The relation between lifelong physical activity at work and during leisure-time and the risk of renal cell cancer (RCC) was analyzed in a case-control study conducted in Italy between 1992 and 2004. Cases were 767 subjects with incident, histologically confirmed RCC, and controls were 1,534 patients hospitalized for acute nonneoplastic conditions.
Odds ratios (OR) and 95% confidence intervals (CI) for RCC were computed by multiple logistic regression models, conditioned on study center, sex and age, and adjusted for main covariates. Compared to the lowest level of occupational physical activity, the multivariate OR of RCC for the highest level were 0.65 (95% CI 0.49-0.87) at age 12 years, 0.67 (95% CI 0.53-0.84) at age 15-19, 0.74 (95% CI 0.59-0.93) at age 30-39 and 0.71 (95% CI 0.55-0.92) at age 50-59 years, with significant inverse trends in risk.
The inverse association was consistent in strata of sex, age at diagnosis, body mass index, smoking habit and alcohol drinking. No significant association was found for leisure-time physical activity. The inverse association between occupational physical activity and RCC risk, if real, may be related to the effects of insulin-like growth factors, or lipid peroxidation and about 9% of cases of RCC in Italy could be avoided by increasing physical activity.
However the inverse association might involve confounding by indirect mechanisms, such as body composition or other social class correlates.
International Journal of Cancer
Volume 120, Issue 9 , Pages 1977 – 1980
Lifetime Recreational Exercise Reduces Risk of DCIS
Original Article
Lifetime recreational exercise activity and risk of breast carcinoma in situ
Alpa V. Patel, Ph.D. 1 2, Michael F. Press, M.D. 3, Kathleen Meeske, Ph.D. 1, Eugenia E. Calle, Ph.D. 2, Leslie Bernstein, Ph.D. 1 *
email: Leslie Bernstein ([email protected])
*Correspondence to Leslie Bernstein, Department of Preventive Medicine, University of Southern California, Los Angeles, CA 90033-9035
Fax: (323) 442-1992
Abstract
BACKGROUND
The incidence rates of breast carcinoma in situ (BCIS) have increased dramatically over the past two decades, primarily because of increased mammography screening. Ductal carcinoma in situ, which accounts for approximately 85% of BCIS and 10-20% of all breast carcinomas, is generally recognized as the final step in the progression to invasive disease.
To the authors’ knowledge, few studies have been conducted to date to evaluate BCIS risk factors. Because of its potential effects on circulating sex hormones, physical activity has been proposed as a modifiable risk factor for invasive breast carcinoma. However, the relation to BCIS risk is poorly understood.
METHODS
The authors analyzed data from a population-based case-control study conducted in Los Angeles County. Personal interviews were conducted with 567 white and black women (age range, 35-64 years) who had been newly diagnosed with BCIS between March 1, 1995 and May 31, 1998 and with 1026 control subjects, of whom 616 were screened within 2 years of identification.
RESULTS
After excluding unscreened control subjects (n = 410) and adjusting for potential confounding factors, the risk of BCIS was approximately 35% lower among women with any exercise activity compared with inactive women, although no significant trend was observed.
The association between exercise activity and the risk of BCIS was modified by a family history of breast carcinoma. No reduction in risk was observed among women reporting a first-degree family history of breast carcinoma (homogeneity of trends P value = 0.02).
CONCLUSIONS
The findings of the current study suggest that exercise activity may modify the risk of BCIS, particularly among women without a family history of breast carcinoma.
Cancer 2003.
Volume 98, Issue 10 , Pages 2161 – 2169
Original Article
Lifetime recreational exercise activity and risk of breast carcinoma in situ
Alpa V. Patel, Ph.D. 1 2, Michael F. Press, M.D. 3, Kathleen Meeske, Ph.D. 1, Eugenia E. Calle, Ph.D. 2, Leslie Bernstein, Ph.D. 1 *
- Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, California
- Department of Epidemiology and Surveillance Research, American Cancer Society, Atlanta, Georgia
- Department of Pathology, University of Southern California Keck School of Medicine, Los Angeles, California
email: Leslie Bernstein ([email protected])
*Correspondence to Leslie Bernstein, Department of Preventive Medicine, University of Southern California, Los Angeles, CA 90033-9035
Fax: (323) 442-1992
Abstract
BACKGROUND
The incidence rates of breast carcinoma in situ (BCIS) have increased dramatically over the past two decades, primarily because of increased mammography screening. Ductal carcinoma in situ, which accounts for approximately 85% of BCIS and 10-20% of all breast carcinomas, is generally recognized as the final step in the progression to invasive disease.
To the authors’ knowledge, few studies have been conducted to date to evaluate BCIS risk factors. Because of its potential effects on circulating sex hormones, physical activity has been proposed as a modifiable risk factor for invasive breast carcinoma. However, the relation to BCIS risk is poorly understood.
METHODS
The authors analyzed data from a population-based case-control study conducted in Los Angeles County. Personal interviews were conducted with 567 white and black women (age range, 35-64 years) who had been newly diagnosed with BCIS between March 1, 1995 and May 31, 1998 and with 1026 control subjects, of whom 616 were screened within 2 years of identification.
RESULTS
After excluding unscreened control subjects (n = 410) and adjusting for potential confounding factors, the risk of BCIS was approximately 35% lower among women with any exercise activity compared with inactive women, although no significant trend was observed.
The association between exercise activity and the risk of BCIS was modified by a family history of breast carcinoma. No reduction in risk was observed among women reporting a first-degree family history of breast carcinoma (homogeneity of trends P value = 0.02).
CONCLUSIONS
The findings of the current study suggest that exercise activity may modify the risk of BCIS, particularly among women without a family history of breast carcinoma.
Cancer 2003.
Volume 98, Issue 10 , Pages 2161 – 2169
