BC CANCER SOCIETY TESTS FOR NHL:
New (2007) study shows environmental contaminants increase risk of non-Hodgkin lymphoma
BC Cancer Agency study largest of its kind to date
A study by BC Cancer Agency scientists provides new evidence that environmental contaminants – organochlorine pesticides and polychlorinated biphenyls (PCBs) – increase the risk of non-Hodgkin lymphoma (NHL). The study, the largest of its kind to date, will be published later this week in the International Journal of Cancer.
“We know that the incidence of non-Hodgkin lymphoma has been steadily rising for the past 30 years worldwide, but there hasn’t been clear evidence to explain the increase,” says Dr. John Spinelli, lead author and a senior scientist at the BC Cancer Agency, an agency of the Provincial Health Services Authority. “Our study helps to provide answers to this puzzle by showing a strong link between these specific environmental contaminants and this particular type of cancer.”
“We are also seeing incidence rates for NHL leveling off in recent years, and this provides further evidence that these contaminants are important because many of these chemicals are no longer in use or are being used at reduced and highly controlled levels,” adds Dr. Spinelli.
Dr. Spinelli and his team collected blood samples from close to 900 British Columbians – half with NHL and the other half without – and tested the samples for exposure to organochlorine pesticides and PCBs. Study participants also answered a questionnaire about demographic characteristics, sunlight exposure, medical history, and other potential risk factors.
Participants with NHL showed much higher levels of environmental contaminants than the control group. Individuals who had the highest total exposure to PCB showed twice the risk of NHL compared to those with the lowest exposure. The strongest association was observed for oxychlordane (a by-product of the pesticide chlordane). Individuals with the highest levels of oxychlordane had 2.7 times the risk of NHL compared to those with the lowest exposure.
“Looking strictly at environmental factors won’t provide the full picture,” said Dr. Spinelli. “Our next step is to identify genetic factors that make individuals more susceptible to these environmental contaminants. In this way, we may be able to determine the mechanism by which contaminants increase the risk for lymphoma, and this knowledge may help to identify environmental risk factors earlier.”
Exposure to organochlorine residuals can occur through the diet. Today in Canada, PCBs are only allowed to be used as insulating fluid in existing electrical equipment. In the past they have been used as flame retardants, hydraulic fluid, lubricating and cutting oil, and additives in pesticides, paints, and carbonless paper. Most organochlorine pesticides have been banned in Canada, but many are still in use in other parts of the world.
Environmental data contained in Ministry of Environment State of the Environment reports shows that more stringent regulation reduced the quantity of PCBs in use in Canada by 54% between 1992 and 2003. In British Columbia, PCB and organochlorine pesticide (i.e. chlordane) content in Great Blue Heron eggs has shown a similar reduction of up to 80% in eggs collected between 1977 and 1999.
“This study is very important because it adds to our understanding of how exposure to chemicals that have become very common in our environment increases our risk of developing lymphoma,” says Dr. Joseph Connors, Chair of the Lymphoma Tumour Group at the BC Cancer Agency and co-investigator on the study.
The study is funded by the Canadian Cancer Society through the National Cancer Institute of Canada, and the Canadian Institutes of Health Research. One of the authors, Carmen Ng, was supported by the Michael Smith Foundation for Health Research. The BC Cancer Foundation provides core funding for research at the BC Cancer Agency.
In 2007, an estimated 966 British Columbians will be diagnosed with non-Hodgkin lymphoma and 383 will die of it. One in 54 females and one in 44 males is expected to develop non-Hodgkin lymphoma during their lifetime. One in 119 females and one in 92 males is expected to die of Non-Hodgkin lymphoma.
The BC Cancer Agency, an agency of the Provincial Health Services Authority, is committed to reducing the incidence of cancer, reducing the mortality from cancer, and improving the quality of life of those living with cancer. It provides a comprehensive cancer control program for the people of British Columbia by working with community partners to deliver a range of oncology services, including prevention, early detection, diagnosis and treatment, research, education, supportive care, rehabilitation and palliative care. The BC Cancer Foundation raises funds to support research and enhancements to patient care at the BC Cancer Agency.
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BC Cancer Agency
Toll-free: 1.800.663.3333, ex 6272
The reasons for the development of NHL are not known. Immune suppression may play a role in some cases.
People who have the human immunodeficiency virus (HIV) have a higher risk of developing lymphoma. The bacterium Helicobacter pylori is associated with the development of mucosa-associated lymphoid tissue (MALT) lymphoma in the stomach wall. Exposure to certain viruses, such as the Epstein Barr virus and the human T-lymphotropic virus (HTLV), are also associated with NHL.
Some studies suggest that exposure to certain ingredients in herbicides and pesticides may be linked to NHL, but these specific relationships are still under study. About a dozen uncommon, inherited syndromes can predispose individuals to later development of NHL. These risk factors explain only a small proportion of cases.
Occupational Exposures and
Non-Hodgkin’s Lymphoma in Southern Sweden
ERIC DRYVER, MD, LARS BRANDT, MD, PHD, TIMO KAUPPINEN, PHD,
HÅKAN OLSSON, MD, PHD
Table 1 illustrates the breakdown by age and gender of
the 2,169 individuals (859 cases and 1,310 controls)
included in this study. Of the study population, 56% were
men, and the mean age for men and for women was 62
years. Over 98% of the controls were within one year of
age of their matched cases. Tables 2–7 illustrate the odds
ratios (ORs) for NHL and the associated 95% confidence
intervals (CIs) of various exposures and occupations.
Exposures to gasoline (OR 1.92; CI 1.20, 3.08), solvents
(OR 1.59; CI 1.11, 2.28), and other oil products
(OR 1.54; 1.01, 2.36) for more than five years were associated
with increased risks of NHL (Table 2). The occupations
of automobile mechanic (OR 1.82; CI 1.18,
2.81) and painter (OR 1.77; CI 1.13, 2.76) were also
related to increased NHL risks. Job-related exposures
to aliphatic and alicyclic hydrocarbons (OR 1.75, CI
1.03, 2.99), aromatic hydrocarbons (OR 1.45; CI 1.13,
1.86), and other organic solvents apart from chlorinated
hydrocarbon solvents (OR 1.41; CI 1.11, 1.80)
were as well, and increasing degrees of exposures to
aromatic hydrocarbons appeared to confer an increasing
risk of NHL (Table 3).
On the other hand, there were no significant associations
between an increased risk of NHL and the selfreported
exposures to insecticides or pesticides (OR
0.76; CI 0.43, 1.33), herbicides (OR 0.95, CI 0.66, 1.38),
fertilizers (OR 0.92; CI 0.66, 1.28), or farm animals
(OR 0.75; CI 0.63, 0.90) (Table 4). Nor was there an
association between NHL and the occupations of farming
(OR 0.86; CI 0.67, 1.09) or forestry (OR 0.97; CI
0.69, 1.38) or the matrix-derived exposures to animal
dust (OR 0.83; CI 0.62, 1.12) or pesticides (OR 1.16; CI
Some studies have reported an association between
adult NHL and gardening, farming, or exposure to animals,
33–37 while other studies have not confirmed such
an association.38–41 The putative increased risk of NHL
among farmers has been attributed in part to exposures
to pesticides (insecticides, herbicides, or fungicides),
which some studies have found to be associated
with an increased risk of adult NHL.38,42–47 In particular,
a recent Swedish study reported increased NHL
risks with exposures to herbicides, pesticides, and
fungicides.48 Other studies, however, have not demonstrated
such an association.49–56 Some studies have
found an absence of increased risk of NHL with farming
yet an increased risk of NHL with exposure to herbicides
or cows,38,57 while other studies have focussed
on the controversies themselves.58–60
Our analyses reveal no increased risk of NHL with
the self-reported occupations of farmer, gardener, or
forester; with the self-reported exposures to pesticides
or farm animals; or with the matrix-derived exposure to
pesticides or animal dust. In fact, some of those exposures
appeared to be protective against NHL, e.g., exposure
to farm animals. Due to the climatic conditions in
Scandinavia, pesticides are used only at certain times
during the year and at relatively low levels. In fact, the
group exposure level to pesticides among farmers was
below the 0.01 unit threshold used in this study, explaining
the discrepancy beween the number of individuals
self-reporting pesticide exposures (20 cases, 40 controls)
and the number of individuals exposed to pesticides
according to FINJEM (12 cases, 16 controls).
Non-Hodgkin lymphomas (NHL) are among the few neoplasms whose incidence and mortality have been rising in Europe and North America over the last few decades. To update trends from NHL, we considered mortality data up to 2004 in several European countries, and for comparative purpose in the USA and Japan. We also analyzed patterns in incidence for selected European countries providing national data. In most European countries, NHL mortality rose up to the mid 1990s, and started to level off or decline in the following decade. The rates were, however, still increasing in eastern Europe. Overall, in the European Union, mortality from NHL declined from 4.3/100,000 to 4.1 in men and from 2.7 to 2.5 in women between the late 1990s and the early 2000s. Similarly, NHL mortality rates declined from 6.5/100,000 to 5.5 in US men and from 4.2 to 3.5 in US women. In most countries considered, NHL incidence rates rose up to 1995-99, while they tended to level off or decline thereafter, with particular favorable patterns in countries from northern Europe. Thus, the epidemic of NHL observed during the second half of the 20th century has now started to level off in Europe as in other developed areas of the world.
Reproductive Factors and Non-Hodgkin Lymphoma Risk in the California Teachers Study
Women in the California Teachers Study cohort provided detailed data in 1995–1996 on reproductive history. Follow-up through 2007 identified 574 women with incident B-cell NHL. Hazard rate ratios (RR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models to assess associations between reproductive factors and all B-cell NHL combined, diffuse large B-cell lymphomas, follicular lymphomas, and B-cell chronic lymphocytic leukemias/small lymphocytic lymphomas. Pregnancy was marginally associated with lower risk of B-cell NHL (RR = 0.84, 95% CI = 0.68–1.04). Much of the reduction in risk was observed after one full-term pregnancy relative to nulligravid women (RR = 0.75, 95% CI = 0.54–1.06; P for trend <0.01), particularly for diffuse large B-cell lymphomas (P for trend = 0.13), but not among women who had only incomplete pregnancies. Age at first full-term pregnancy was marginally inversely associated with B-cell NHL risk overall (P for trend = 0.08) and for diffuse large B-cell lymphomas (P for trend = 0.056). Breast feeding was not associated with B-cell NHL risk overall or by subtype.
Full-term pregnancy and early age at first full-term pregnancy account for most of the observed reduction in B-cell NHL risk associated with gravidity. Pregnancy-related hormonal exposures, including prolonged and high-level exposure to progesterone during a full-term pregnancy may inhibit development of B-cell NHL.