Obituary of Epidemiology Legend: Brian MacMahon

Passing of Brian MacMahon, MD, MBChB, DPH, PhD

Brian MacMahon, chair of the Department of Epidemiology at Harvard School of Public Health for 31 years, passed away on December 5th, 2007 at the age of 84.

Brian was a giant in the field of cancer epidemiology and became particularly recognized for his work on breast cancer etiology. In 1970, he was the lead author on a renowned international collaborative study that detailed an association between risk of breast cancer and the age at which women gave birth to their first child. The findings provided new insight into the protective mechanisms of pregnancy and prompted broader thinking about the causes of breast cancer.

In 1960, Brian co-authored Epidemiologic Methods with Tom Pugh. This textbook became Epidemiology: Principles and Methods, which is widely recognized as a landmark epidemiology textbook in the U.S.

In addition to his cancer studies, Brian was well-known for his papers on pyloric stenosis in infants. This condition interferes with the ability to digest food. At a time when genes were the primary focus of research underlying pyloric stenosis, Brian’s research shed light on associated environmental factors.

In the 1940s, Brian attended the University of Birmingham, England, earning diplomas of the Royal Colleges of Physicians and Surgeons, as well as an MB, ChB, and DPH. From 1946 to 1948, he worked as a ship’s doctor in the English Merchant Navy. In 1952, he earned a PhD in social medicine from the University of Birmingham. The following year, he came to HSPH, achieving a master’s degree in epidemiology in 1953. Two years later, he obtained an MD with honors from the University of Birmingham.

Brian held appointments at the University of Birmingham and at the State University of New York, Downstate Medical Center, before accepting the position as head of the HSPH Department of Epidemiology in 1958. He served as the department’s leader until 1989, passing the mantle to Professor Dimitrios Trichopoulos.

In 1974, he was appointed Professor of Public Health at the University of Hawaii at Manoa, School of Public Health. In 1976, he was appointed Henry Pickering Walcott Professor of Epidemiology at HSPH. From 1977 to 1978, he served as Associate Dean for Academic Affairs at the School.

Brian received the National Divisional Distinguished Service Award from the American Cancer Society in 1971 and was elected to the Institute of Medicine in 1973. He was conferred the John Snow Award from the American Public Health Association in 1980, and he received the Charles S. Mott Prize from the General Motors Cancer Research Foundation in 1992. He received honorary doctorates from the University of Athens, the State University of New York, and the University of Birmingham, England.

A native of England, Brian became a naturalized U.S. citizen in 1962.

WHO- International Agency for Research on Cancer (IARC) classifications of carcinogens (cancer causing agents)

Definitions of IARC classifications of carcinogens:

Group 1: The agent is carcinogenic to humans.
This category is used when there is sufficient evidence of carcinogenicity in humans. Exceptionally, an agent may be placed in this category when evidence of carcinogenicity in humans is less than sufficient but there is sufficient evidence of carcinogenicity in experimental animals and strong evidence in exposed humans that the agent acts through a relevant mechanism of carcinogenicity.

Group 2.
This category includes agents for which, at one extreme, the degree of evidence of carcinogenicity in humans is almost sufficient, as well as those for which, at the other extreme, there are no human data but for which there is evidence of carcinogenicity in experimental animals. Agents are assigned to either Group 2A (probably carcinogenic to humans) or Group 2B (possibly carcinogenic to humans) on the basis of epidemiological and experimental evidence of carcinogenicity and mechanistic and other relevant data. The terms probably carcinogenic and possibly carcinogenic have no quantitative significance and are used simply as descriptors of different levels of evidence of human carcinogenicity, with probably carcinogenic signifying a higher level of evidence than possibly carcinogenic.

Group 2A: The agent is probably carcinogenic to humans.
This category is used when there is limited evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals. In some cases, an agent may be classified in this category when there is inadequate evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals and strong evidence that the carcinogenesis is mediated by a mechanism that also operates in humans. Exceptionally, an agent may be classified in this category solely on the basis of limited evidence of carcinogenicity in humans. An agent may be assigned to this category if it clearly belongs, based on mechanistic considerations, to a class of agents for which one or more members have been classified in Group 1 or Group 2A.

Group 2B: The agent is possibly carcinogenic to humans.
This category is used for agents for which there is limited evidence of carcinogenicity in humans and less than sufficient evidence of carcinogenicity in experimental animals. It may also be used when there is inadequate evidence of carcinogenicity in humans but there is sufficient evidence of carcinogenicity in experimental animals. In some instances, an agent for which there is inadequate evidence of carcinogenicity in humans and less than sufficient evidence of carcinogenicity in experimental animals together with supporting evidence from mechanistic and other relevant data may be placed in this group. An agent may be classified in this category solely on the basis of strong evidence from mechanistic and other relevant data.

Group 3: The agent is not classifiable as to its carcinogenicity to humans.
This category is used most commonly for agents for which the evidence of carcinogenicity is inadequate in humans and inadequate or limited in experimental animals.
Exceptionally, agents for which the evidence of carcinogenicity is inadequate in humans but sufficient in experimental animals may be placed in this category when there is strong evidence that the mechanism of carcinogenicity in experimental animals does not operate in humans.
Agents that do not fall into any other group are also placed in this category.
An evaluation in Group 3 is not a determination of non-carcinogenicity or overall safety. It often means that further research is needed, especially when exposures are widespread or the cancer data are consistent with differing interpretations.

Group 4: The agent is probably not carcinogenic to humans.
This category is used for agents for which there is evidence suggesting lack of carcinogenicity in humans and in experimental animals. In some instances, agents for which there is inadequate evidence of carcinogenicity in humans but evidence suggesting lack of carcinogenicity in experimental animals, consistently and strongly supported by a broad range of mechanistic and other relevant data, may be classified in this group.

IARC: cancer hazards associated with shiftwork, painting and firefighting

IARC Monographs Programme finds cancer hazards associated with shiftwork, painting and firefighting

After a thorough review and discussion of the published scientific evidence, an expert Working Group convened by the IARC Monographs programme has concluded that
· Shiftwork that involves circadian disruption is probably carcinogenic to humans (Group 2A).
· Occupational exposure as a painter is carcinogenic to humans (Group 1).
· Occupational exposure as a firefighter is possibly carcinogenic to humans (Group 2B).
These three occupations involve complex exposure patterns that make it difficult to attribute risk to specific factors. The Working Group, comprising 24 scientists from 10 countries, met at the International Agency for Research on Cancer (IARC), the cancer research agency of the World Health Organization.
A summary of these conclusions is being published in the December issue of The Lancet Oncology. Full results will be published next year as volume 98 of the IARC Monographs.



Shiftwork that involves circadian disruption is “probably carcinogenic to humans”

Epidemiological studies have found that long-term nightworkers have a higher risk of breast cancer risk than women who do not work at night. These studies have involved mainly nurses and flight attendants. The studies are consistent with animal studies that demonstrate that constant light, dim light at night, or simulated chronic jet lag can substantially increase tumour development. Other experimental studies show that reducing melatonin levels at night increases the incidence or growth of tumours.

These results may be explained by the disruption of the circadian system that is caused by exposure to light at night. This can alter sleep-activity patterns, suppress melatonin production, and disregulate genes involved in tumour development. Among the many different patterns of shiftwork, those that include nightwork are most disruptive to the circadian system.
"Nearly 20% of the working population in Europe and North America is engaged in shiftwork, which is most prevalent in the health-care, industrial, transportation, communications, and hospitality sectors: To date, most studies have focussed on breast cancer in nurses and flight attendants. Now more studies are needed to examine this potential risk in other professions and for other cancers," noted Dr Cogliano, Head of the IARC Monographs Programme.


Occupational exposure as a painter is “carcinogenic to humans”

Epidemiological studies of painters have consistently found small but significant increases in the risk of lung cancer and bladder cancer. In addition, several studies of painters have found increased levels of genetic damage.
Four of five case-control studies found significant increases in childhood leukaemia associated with maternal exposure before or during pregnancy, although findings were inconsistent for lymphatic and haematopoietic cancers in the painters themselves.
Painters are exposed to numerous chemical solvents, pigments, and additives. They can also be exposed to other workplace hazards such as asbestos and crystalline silica. The available information is not specific enough to identify particular agents as the cause of the excess lung or bladder cancers. It also cannot be determined whether the cancer risks have increased or decreased with changes in the solvents, pigments, and additives used in paints.


Occupational exposure as a firefighter is “possibly carcinogenic to humans”

Epidemiologic studies of firefighters have noted excess cancer risks compared with the general population. Consistent patterns are difficult to discern due to the large variations in exposure across different types of fires and different groups of firefighters. Relative risks were consistently increased, however, for three types of cancer: testicular cancer, prostate cancer, and non-Hodgkin lymphoma.

Acute and chronic inflammatory respiratory effects have been noted in firefighters, and this would provide a plausible mechanism for respiratory carcinogenesis. Firefighters are exposed to numerous toxic chemicals, including many known or suspected carcinogens. These intermittent exposures can be intense, and short-term exposure levels can be high for respirable particulate matter and for several carcinogens, notably benzene, benzo[a]pyrene, 1,3-butadiene, and formaldehyde.



What is new, and what do these results mean to me?
"These are IARC’s first evaluations of shiftwork and firefighting. Because there is credible evidence linking these occupations with increased risks of cancer, it is important that further studies be conducted to better identify what it is about such occupations that may increase the risk of cancer so that preventive measures can be implemented to avoid such risks", concluded Dr Peter Boyle, Director of the International Agency for Research on Cancer.

Occupational exposure as a painter has been classified since 1989 as carcinogenic to humans, and this new evaluation has linked painting to lung cancer and bladder cancer. The new evaluation also suggests that maternal exposure may be associated with childhood leukaemia. It is important that further studies be conducted in this area to confirm whether this risk is real and to identify precautionary measures that are appropriate to consider.


(from IARC press release 180a)

Abstract Submission: 2008 SER Annual Meeting, Chicago, IL

Abstract submission is now open for the 2008 Society for Epidemiologic Research (SER) Annual Meeting, June 24(eve) - 27 in Chicago, IL.

http://www.epiresearch.org/abstracts/

For more information, contact:

Jacqueline C Brakey
for the SER Executive Committee
PH: 801-525-0231
meeting@epiresearch.org