Tag Archives: cancer

Rotating night shift work is linked to several diseases

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"MoonClouds" by Smatprt - Own work. Licensed under CC BY-SA 3.0 via Wikimedia Commons - http://commons.wikimedia.org/wiki/File:MoonClouds.JPG#mediaviewer/File:MoonClouds.JPG
“MoonClouds” by Smatprt – Own work. Licensed under CC BY-SA 3.0 via Wikimedia Commons – http://commons.wikimedia.org/wiki/File:MoonClouds.JPG#mediaviewer/File:MoonClouds.JPG

Doing activities and working during the night affects the circadian system, causing sleeping disorders thus severely affecting health.

A large prospective study has been published this month on the American Journal of Preventive Medicine using data from the Nurses’ Health Study (NHS), linking night shift rotation, cardiovascular diseases (CVDs), and some types of cancer mortality1. The NHS was established in 1976 enrolling more than 100,000 nurses aged 30–55 years. Women with previous CVD or cancer or nurses who did not provide information about their shift were excluded from the study; therefore only the information on 74,862 nurses was used during 22 years of follow-up.

The nurses were classified in four groups according to the years of rotating night shift work: never, 1–5, 6–14, and >15 years. Working rotating night shifts for more than five years significantly correlated with all-cause, CVD, in particular ischemic heart disease, and some type of cancer mortality. Lung cancer was the most significantly correlated cause of cancer mortality, followed by colorectal and breast cancers, but overall cancer mortality was not significantly increased in nurses who worked rotating night shift for more than five years. Also lifestyle factors—such as physical activity, dietary habits, and smoking—body mass index, diabetes, cholesterol were considered, but no significant correlations were identified. Women working rotating night shifts tended to be older, be more physically active, drink less alcohol, eat less cereal, and were more likely to have diabetes, hypertension, and hypercholesterolemia than women without night shift work.

Undoubtedly working rotating night shifts disrupts circadian rhythms, causing not only sleeping pattern disorders, but also affecting health. Many studies have correlated night work and exposure to light during nighttime with cardiovascular diseases and cancer, thus the WHO classified night work as a probable carcinogen in 19972,3,4. The molecular mechanism underlying this correlation is not fully known. Circadian rhythms are controlled by melatonin, the hormone produced during nighttime by the pineal gland in the brain. Any disturbance in sleeping pattern, or exposure to light during night affects melatonin production and the pathways controlled by this hormone. Melatonin has been involved in several processes (metabolism, immune response, reproduction, etc.); therefore it is not surprising that this hormone can affect several diseases.

Although in this study only nurses were considered and no other professions, this is the largest prospective cohort available worldwide with a high proportion of women working rotating night shift and with a very long follow-up period, thus making it a reliable collection of data without confounding occupation-related diseases.

Moral of the story: Don’t work during the night!

 

1Total and Cause-Specific Mortality of U.S. Nurses Working Rotating Night Shifts. Gu F, Han J, Laden F, Pan A, Caporaso NE, Stampfer MJ, Kawachi I, Rexrode KM, Willett WC, Hankinson SE, Speizer FE, Schernhammer ES. Am J Prev Med. 2015 Jan 6. pii: S0749-3797(14)00623-0. doi: 10.1016/j.amepre.2014.10.018

2Melatonin, sleep disturbance and cancer risk. Blask DE.Sleep Med Rev. 2009 Aug;13(4):257-64. doi: 10.1016/j.smrv.2008.07.007. Epub 2008 Dec 17. Review.

3Rotating night shifts and risk of breast cancer in women participating in the nurses’ health study.Schernhammer ES, Laden F, Speizer FE, Willett WC, Hunter DJ, Kawachi I, Colditz GA.J Natl Cancer Inst. 2001 Oct 17;93(20):1563-8.

4Carcinogenicity of shift-work, painting, and fire-fighting. Straif K, Baan R, Grosse Y, Secretan B, El Ghissassi F, Bouvard V, Altieri A, Benbrahim-Tallaa L, Cogliano V. Lancet Oncol. 2007 Dec;8(12):1065-6.

See also http://damianodemaria.scienceblog.com/80/light-exposure-at-night-induces-resistance-to-therapy-in-breast-cancer/

Smoking Increases the Risk of Estrogen Receptor Positive Breast Cancer

Cancer, , , , , , , , , , , , ,

A study from the Fred Hutchinson Cancer Center shows that smoking among young women may increase the risk of developing estrogen receptor (ER)-positive breast cancer, but not triple negative breast cancer (TNBC).

The group led by Dr. Christopher Li conducted a population-based study among women from 22 to 44 years old diagnosed with breast cancer between January 2004 and June 2010 in the July 2014. The patients were 938 women in the control group, 778 in the ER-positive group, and 182 in the TNBC group. The researchers interviewed the patients and obtained detailed information about different aspects of their lifestyle—reproductive history, demographics, physical activity, alcohol drinking, medical history—and smoking habits—regency, number of cigarettes smoked per day, ages when smoked. The patients were divided in never smokers and ever smokers (current or former). The ever-smoker group was further categorized based on the number of pack of cigarettes smoked per year.

Smokers had increased risk of developing breast cancer overall (30%), without any significative change when the total number of years of smoking or the age women first started were considered. Although the small number of TNBC cases, the risk was associated with ER-positive breast cancer and not with TNBC. However, among current smokers, women who had been smoking for more than fifteen years had 50% increased risk of developing ER-positive breast cancer compared with women who had been smoking for fewer years. Of note is that, in women who had not been smoking for more than ten years the risk of developing ER-positive breast cancer decreased dramatically.

Various studies have correlated smoking to the risk of breast cancer, but this is one of the few studies linking smoking to ER-positive breast cancers in premenopausal women. Metabolites of tobacco, found in the breast fluid and breast tissue of current smokers, have been shown to have an estrogenic effect in in vitro studies, thus explaining the increased risk of ER-positive breast cancer in young women found in this research.

Smoking has several adverse effects and has been associated to different cancers. This is not only a study that supports previous reports linking smoking to breast cancer, but this study links smoking to a specific subtype of breast cancer (ER-positive) in young women.

 

Masaaki Kawai, Kathleen E. Malone, Mei-Tzu C. Tang, Christopher I. Li. Height, body mass index (BMI), BMI change, and the risk of estrogen receptor-positive, HER2-positive, and triple-negative breast cancer among women ages 20 to 44 years. Cancer, 2014

Resveratrol: just a fair-weather friend?

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JUne 2014Since its first mention in a Japansee article in 19391, over the years many beneficial effects have been attributed to the natural compound, resveratrol—anticancer, anti-inflammatory, anti-aging—which is even used in skincare cosmetic. Although a large number of studies suggest its health benefits, recently some reports have been questioning these potentials.

Resveratrol is a natural phenol and antioxidant compound found in various colored vegetables and fruit, especially in the skin of red grape. Its name comes probably from the combination if the term resorcinol (chemical compund) and Veratrum (the plant where resveratrol was first isolated). It is thought to influence inflammation, aging, neuronal degeneration, and metabolism through the serine deacetylase, sirtuin-1 (SIRT-1), the cAMP pathway, or AMP-activated protein kinase2. However the exact mechanism of action is not known. A new role for resveratrol as a partial agonist of the estrogen receptor alpha (ERalpha) has been recently described3. According to this study, resveratrol binds to the ERalpha that is recruited to the interleukin-6 (IL-6) promoter and alters the binding of coregulators, such as SIRT-1, and the activity of transcriptional activators, leading to reduced inflammation. Resveratrol was identified in a previous screening for ERalpha agonists that inhibit IL-6 transciption4; thus resveratrol may have a selective role on the ERalpha pathway, inhibiting inflammation without promoting cell proliferation.

The amount of resveratrol found in foods varies greatly. It is mainly found in the skin of red grapes, red wine, peanuts, berries, and in lower amount in cocoa powder and dark chocolate5. However, the amount of resveratrol in foods is thought to be not enough to justify and mediate its effects. To understand whether resveratrol levels present in the diet can influence inflammation, cancer, cardiovascular disease, and mortality in humans, a prospective cohort study has been conducted in the Chianti region in Italy (InCHIANTI—“Aging in the Chianti Region”), in a population-based sample of 783 community-dwelling men and women 65 years or older who consume a diet rich in resveratrol6. The group of researchers, who have been studying aging in this population for fifteen years, measured the concentration of resveratrol metabolites present in the urine and found that it was not associated with inflammatory markers, cardiovascular disease, or cancer. This study shows that the amount of resveratrol present in the diet is not responsible for beneficial health effects. It is possible that the health benefits that come from the diet consumed in that region are not due to resveratrol, but to other substances present in the food. On the other hand resveratrol is rapidly metabolized in sulfate and glucuronide conjugates and it has long been believed that this could limit its bioavailability. However, a study from the University of Leicester shows that resveratrol is not rendered ineffective after it is metabolized by the body: it can be generated by resveratrol sulfate and be even more effective than the un-metabolized compound7.

Supplements that contain high quantity of resveratrol are available in the market. However, people should be careful with them, because we still don’t know the repercussions of high amount of resveratrol on human health. A very recent study published on the June issue of The FASEB Journal shows that the use of resveratrol during pregnancy can have beneficial effects on the blood flow in the placenta and on the liver function (decreased placental inflammation and liver triglyceride deposition), but can increase fetal pancreatic mass and exocrine proliferation, leading to unknown consequences on the development of the fetus8.

To date, there are not definitive studies on the benefits of resveratrol. The literature is full of controversial or incomplete reports. Therefore, be careful in listening to advertisements that sell resveratrol as a health serum.

1Takaoka M, Resveratrol, a new phenolic compound, from Veratrum grandiflorum. M Takaoka, Journal of the Chemical Society of Japan, 193 (2012):1090-1100.

2Tennen RI, Michishita-Kioi E, Chua KF. “Finding a target for resveratrol”. Cell 2012,148 (3): 387–9.

3Nwachukwu J,Srinivasan S, Bruno NE, Parent AA, Hughes TS, Pollock JA, Gjyshi O, Cavett V, Nowak J, Garcia-Ordonez RD, Houtman R, Griffin PR, Kojetin DJ, Katzenellenbogen JA, Conkright MD, Nettles KW. Resveratrol modulates the inflammatory response via an estrogen receptor-signal integration network. eLife, (2014).

4Srinivasan S., Nwachukwu J.C., Parent AA, Cavett V, Nowak J, Hughes TS, Kojetin DJ, Katzenellenbogen JA, and Nettles KW. Ligand-binding dynamics rewire cellular signaling via estrogen receptor-alpha. Nat Chem Biol (2013) 9, 326-332.

5Hurst WJ, Glinski JA, Miller KB, Apgar J, Davey MH, Stuart DA. “Survey of the trans-resveratrol and trans-piceid content of cocoa-containing and chocolate products”. Journal of Agricultural and Food Chemistry (2008) 56 (18): 8374–8.

6Semba RD, Luigi Ferrucci L, Bartali B, Urpí-Sarda M, Zamora-Ros R, Sun K, Cherubini A, Bandinelli S, Andres-Lacueva C. Resveratrol Levels and All-Cause Mortality in Older Community-Dwelling Adults. JAMA Internal Medicine, (2014) May 12.

7Patel KR, Andreadi C, Britton RG, Horner-Glister E, Karmokar A, Sale S, Brown VA, Brenner DE, Singh R, Steward WP, Gescher AJ and Brown K. Sulfate Metabolites Provide an Intracellular Pool for Resveratrol Generation and Induce Autophagy with Senescence. Science Translational Medicine, (2013) Oct 2;5(205).

8Roberts VHJ, Pound LD, Thorn SR, Gillingham MB, Thornburg KL, Friedman JE, Frias AE, and Grove KL. Beneficial and cautionary outcomes of resveratrol supplementation in pregnant nonhuman primates. FASEB J. (2014) June 28:2466-2477.

Fruit and vegetable consumption: a longer life

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We all know that fruit and vegetables are healthy, but did you know that eating vegetables is more effective than eating fruit in reducing mortality?

May 2014A recent study published on Journal of Epidemiology & Community Health1 reports the association of fruit and vegetable consumption with all-cause, cancer, and cardiovascular mortality in 65,226 English people included in the Health Survey for England from 2001 to 2013. Oyebode et al. found that people who consumed more vegetable and fruit were generally older, non-smokers, women, educated, and physically more active than the rest of the population. Fruit and vegetable consumption was inversely correlated with all-cause, cancer, and cardiovascular disease (CVD) mortality, with a threshold of seven or more portions a day for all-cause and CVD mortality, five and less for cancer, and seven or more for CVD. When vegetable and fruit consumption were considered separately, vegetable were more beneficial than fruit on cancer and CVD survival. Specifically, fresh vegetables, salad, fresh fruit, and dried fruit were inversely correlated with mortality; instead canned/ frozen fruit consumption was directly correlated with increased mortality. This could be because some fresh vegetables and all fresh fruit are consumed raw, preserving all their nutrition facts; instead, canned fruit have a high content of sugar that can cause health problems if consumed in excess. As the authors discuss, usually frozen fruit is considered to be equivalent to raw fruit; therefore, the ambiguity of this study might be due to the way the survey was conducted with questions that didn’t distinguish between canned and frozen fruit.

”In 1990, the WHO issued recommendations for a minimum daily intake of 400 g of fruit and vegetables, based on evidence that higher levels were protective against [. . .] CVD and some cancers,”1 leading to various campaigns in Europe, the United States, and Australia for inducing people to consume more vegetables and fruits, not based on any valuable evidence. The present study provides this evidence. Although the study might be missing some information because of the self-report survey, this is the first analysis correlating fruit and vegetable consumption with mortality on a nationwide population.

This report shows that eating seven or more portions of vegetables a day decreases mortality. Unfortunately, vegetables and fruit are more expensive than the majority of unhealthy chips, sauces, or cookies that are sold on the aisles of the grocery stores, leading to a less consumption of vegetable and fruit in low-income houses2. Nutritional campaigns might not be effective in promoting a healthier diet, if the prices of healthy food remain high.

A more incisive policy should be carried out: it should be based on price cut and not only limited to surveys and statistics.

1. Oyebode O., Gordon-Dseagu V., Walker A., Mindell, JS. Fruit and vegetable consumption and all-cause, cancer and CVD mortality: analysis of Health Survey for England data. J Epidemiol Community Health, 31 March 2014

2. Thompson J. ‘Diet and healthy eating’. Chapter 5 In: Craig R, Shelton N, eds. Health Survey for England 2007. Knowledge, attitudes and behaviours. London: NHS Information Centre, 2008;107–48

 

 

The life of adult survivors of childhood cancer

Cancer, , , , , , , , ,

DecemberSurvivors of childhood and adolescent cancer have impaired health-related quality of life (HRQQL) and show accelerated aging.

A team from the St. Jude Children’s Hospital analyzed frailty and health-related symptoms in a large cohort of childhood cancer survivors (CCS) and reported them in two consecutive articles published in the Journal of Clinical Oncology in the last two months 1 -2.

In the first study, the participants were 1,662 survivors with more than 10 years from diagnosis. Among the 12 classes of symptoms considered for HRQQL there were cardiac, pulmonary, motor/movement, pain in head, in back/neck, pain involving sites other than head, neck, and back, sensation abnormalities, learning/memory, anxiety, depression, and somatization. 77%of the subjects reported more than one symptom and more than 50% had pain involving sites other than head, neck and back, and disfigurement. The prevalence of the symptoms was higher in this cohort than in the average population of the same age.

In the second study, frailty was defined by the presence of at least two of the following symptoms: low muscle mass, self-reported exhaustion, low energy expenditure, slow walking speed, and weakness. 1,992 survivors where compared to 341 subjects without cancer and 13.1% of women and 2.9% of men were qualified as frail with an average age of 33 years. Frailty was associated with smoking and body mass index in men, while lifestyle choices didn’t affect frailty in women. Also, the kind of cancer treatment, such as cranial radiation therapy (CRT) and abdominal/pelvic radiation in men and only CRT in women, affected the frailty phenotype. As expected in both sex, frailty was associated with increasing age. Frailty is usually reported in people 65 years old or older, therefore such phenotype indicates early aging.

Both these studies highlight the impact of the disease and of the treatments on CCS’ quality of life.  Advances in cancer treatment resulted in an increased number of survivors, who are facing the long term consequences of these treatments.   The importance of these reports is that they are the first reports studying quality of life and aging in such a large cohort of patients. However they present some limitations. For instance, despite the large cohort, the subjects are all from one institution in the United States. Therefore, to find new correlative associations and elucidate the biological causes and mechanisms triggering this phenotype, in the future the study has to be extended to other institutions and other Countries.

Many studies have been published on this cohort of CCS in the last year from the same group of people highlighting different aspects that impair survivors’ quality of life so accurately. If you’re intrigued after reading this post, I would suggest you to do a search on Pubmed to broaden your knowledge.

1 Huang IC, Brinkman TM, Kenzik K, Gurney JG, Ness KK, Lanctot J, Shenkman E, Robison LL, Hudson MM, Krull KR. Association between the prevalence of symptoms and health-related quality of life in adult survivors of childhood cancer: a report from the st Jude lifetime cohort study. J Clin Oncol. 2013 Nov 20;31(33):4242-51. doi: 10.1200/JCO.2012.47.8867. Epub 2013 Oct 14.

2 Ness KK, Krull KR, Jones KE, Mulrooney DA, Armstrong GT, Green DM, Chemaitilly W, Smith WA, Wilson CL, Sklar CA, Shelton K, Srivastava DK, Ali S, Robison LL, Hudson MM. Physiologic Frailty As a Sign of Accelerated Aging Among Adult Survivors of Childhood Cancer: A Report From the St Jude Lifetime Cohort Study. J Clin Oncol. 2013 Nov 18. [Epub ahead of print]

 

The frightening effect of the word “cancer”

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Did you know that Ductal Carcinoma In Situ (DCIS), noninvasive breast cancer, breast lesion or abnormal cells have all the same meaning? A very recent study from a team of the University of California San Francisco (UCSF) describes the impact of complicated medical terminology on patient treatment preference.

september 2013Since medical terms may sometimes sound too complicated and cryptic, health care provider’s communication with their patients is critical for a full understanding of medical conditions, diagnosis and treatments. In the research letter published on JAMA Internal Medicine on August 26th, Ozanne M. et al.1 explored the effect of Ductal Carcinoma In Situ (DCIS) terminology on the choice of patient treatment.

DCIS is the most common type of non-invasive breast cancer, accounting for the 20-25% of newly diagnosed breast cancers in the United States. It is treated with mastectomy or lumpectomy, with or without radiation therapy, and with or without adjuvant hormonal therapy2. In some low-grade cases, the progression may occur in a very long time frame (5 to 40 years), with no relevant clinical significance during patient’s life. Therefore, in these cases a watchful waiting period has been proposed instead of a treatment, even if it might be difficult to convince of this a patient who has just discovered to have “cancer”.

The team of doctors from UCSF hypothesized that without using the word cancer, the women diagnosed with DCIS might be more prone to non-invasive approaches. They surveyed 394 healthy women with no history of breast cancer and presented them 3 scenarios to describe the diagnosis of DCIS: noninvasive breast cancer, breast lesion or abnormal cells. To all of them was presented the same outcomes and options of treatment (surgery, medication, or active surveillance). They found that when DCIS was described as a high risk condition (breast lesion, or abnormal cells) instead of a cancer, more that 66% of women chose non-surgical treatments, whereas when the term noninvasive cancer was used only 53% of the participants chose a non-surgical option.

As pointed out in the original article, the current study has some limitations, being performed on a restricted cohort of educated and well insured women, different from the cohort of DCIS patients, and without taking into account specific factors, such as tumor grade and age. Although this analysis was performed on healthy women who didn’t have cancer, it suggests that many patients may prefer noninvasive therapies, when allowed to carefully consider risks and treatments, pointing out the importance of the terminology used by health care providers.

Too often, people are confused after leaving their physician’s office and this is something that should not happen, especially when dealing with serious and heterogeneous diseases, such as cancer. Hopefully this study is not a drop in the bucket and will be taken into consideration in the future, leading to a careful elucidation of the puzzling medical dictionary.

1              Omer, Z. B., Hwang, E. S., Esserman, L. J., Howe, R. & Ozanne, E. M. Impact of Ductal Carcinoma In Situ Terminology on Patient Treatment Preferences. JAMA Intern Med, doi:10.1001/jamainternmed.2013.84051731962 [pii] (2013).

2              Virnig, B. A., Wang, S. Y., Shamilyan, T., Kane, R. L. & Tuttle, T. M. Ductal carcinoma in situ: risk factors and impact of screening. J Natl Cancer Inst Monogr 2010, 113-116, doi:10.1093/jncimonographs/lgq024lgq024 [pii] (2010).

 

Cancer is a family affair

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A recent study describes the relationship between Family History of cancer and cancer risk for the same type or for a different type of cancer on a wide network of cases collected in Switzerland and Italy. 

When someone is diagnosed with cancer, members of the family start periodical check-up, frightened by the idea that cancer could easily affect other relatives.   Although approximately only the 7%  of cancers are hereditary with known mutations that imprint the risk of cancer in the genes, scientists often refer to familial cancer. Indeed some type of tumors commonly spread in certain families. However, there are no other hereditary factors -other than gene mutations- known to drive the disease.

An interesting  study published in the Journal  “Annals of Oncology” by Turati et al. 1 last July tries to elucidate the relationship between Family History of cancer (FH) and cancer risk. The researchers provide a quantitative association of FH and risk of developing the same type or a different type of tumor in a cohort of 23000 individuals (11000 controls and 12000 cancer cases) collected in Switzerland and Italy between 1999 and 2009.  They analyzed 13 cancer types (mouth and pharynx, nasopharynx, esophagus, stomach, colorectum, liver, pancreas, larynx, breast, womb, ovaries, prostate and kidneys) and incorporated several information, such as sociodemographic characteristics, lifestyle, dietary habits, and personal medical history.

In all cases, they found higher risk of developing cancer when a first degree relative had a history of the same type of cancer. Interestingly, the researchers found a plethora of associations between cancers of different origin: esophageal cancer and FH of oral and pharyngeal cancer, breast cancer and FH of colorectal and of hemolymphopoietic cancer, ovarian cancer and FH of breast cancer, prostate cancer and FH of bladder cancer.  Some associations were stronger if analyzed in subjects before 60 years old (colorectal and FH of ovarian cancer and prostate cancer or endometrial cancer and FH of stomach cancer).

august 2013Some of these associations were already known. For example, subjects with BRCA1/2 mutations have increased risk of developing breast and ovarian cancer, as well as prostate, colon and pancreatic cancers.  However, as they properly point out in their article, these mutations are associated with an increased risk, but “they are too rare to account for a substantial proportion of common cancers”. They may predispose to cancer, but other factors might concur in the development of a familial cancer. For instance, intrinsic factors, such as genetic polymorphisms occurring in the same family, or extrinsic factors, such as the environment and lifestyle habits, could affect the spread of cancer.  Indeed, alcohol and tobacco are associated with increased risk of developing tumors. In some cases, cancer incidence was found higher in males than in women, in part due to a largest consumption of alcohol and tobacco  among men in the past. These trends might change in the future. On one hand, women now consume as much alcohol and tobacco as men do, leading to a potential higher incidence of cancer in the female population. On the other hand, the anti-tobacco advertisements might have a positive effect and tobacco might  be a limited issue in the future.

Family history of cancer has been studied for a long time, but lack of complete information limited rigorous epidemiological studies. The present study incorporates information about lifestyle and subjects’ characteristics for adjustment purposes which haven’t been considered previously, leading to better insights on how cancer can spread in some families. More analyses of this kind are needed in other population datasets to make a wide correlation between family history and risk of cancer.

We need to be aware that if cancer occurs in one member of a family, in some cases there might be either a genetic or an environmental factor that can predispose other members of the family.  We need to know, to prevent it.

1. Turati, F. et al. Family history of cancer and the risk of cancer: a network of case-control studies. Ann Oncol, doi:mdt280 [pii] 10.1093/annonc/mdt280 (2013).