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Risk Factors for Lymphoma

Last update: 07/03/2010

TOPIC
Risk Factors
| Allergies | Aspirin | Autoimmune Disease | Bacteria H pylori | Benzene | Blood Transfusions | Chemicals  DioxinFamilial (inherited) | Fats | FluorideGasoline | Genetic | Hair Dye | Hormone Replacement Therapy | Immune Suppression | Life Style: Diet / Sunlight | Magnetic Fields | Melanoma | Metals | Mothballs | Nitrates | Pesticides  Psoriasis | Rheumatoid Arthritis | Sjogren's | Smoking (tobacco) | Stress | SV40 Virus | Viral

TOPIC SEARCH: PubMed 

There are many factors associated with the increased risk of developing lymphomas, but no definitive causes have been identified, with the exception of of H pylori infection, which has a causal role in the development of some mucosa-associated lymphatic tissue lymphomas (MALT). 

To many observers, the increase in incidence rates of lymphomas over the past 20 years, and the higher incidence rates in industrialized countries, suggests that environmental factors play a role.  However, with prosperity comes improvement in health care, which can increase the median age of the population (a risk factor) and also the ability to diagnose lymphomas. 

Consider also confounding variables.  For example, and elevated risk associated with exposure to a specific drug, may be from the drug, or from the underlying condition the drug is being used to treat. Also, if the increased risk is small, it could be from chance, so it's important that independent studies validate findings of earlier studies, consistently. 

The etiology or causes of CLL and lymphomas are not yet known. There could be many contributing factors that lead to it development over time, such as advancing age, inherited disposition, exposures to chemicals or radiation, and chance. 

Regarding suspected environmental factors, scientists often study groups that are exposed in the workplace (because these exposures can be estimated with greater assurance), to see if the incidence rates of disease are significantly higher compared to the general population.

 

Full text reports:

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Etiologic heterogeneity (risk factor variation) among NHL subtypes,
Blood.
2008 http://bit.ly/bUDXZw
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Occupation and malignant lymphoma: a population based case control
study in Germany, Occup Environ Med 2006 http://bit.ly/btSkWn
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Environmental and Occupational Causes of Cancer New Evidence, 2005–2007,
Rev Environ Health 2009 http://bit.ly/afBT4S 
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Patterns of autoimmunity and subsequent CLL in Nordic countries,
Blood.
2006  http://bit.ly/d95BDm
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Inherited predisposition to CLL, http://bit.ly/a7dfp8
Expert Rev Hematol.
2008  

Factors associated with an increase risk of developing a lymphoma:  

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Chemical exposures - chronic exposures to dioxins, PCBs, pesticides, solvents, and fertilizers 
 

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Chronic infections - H pylori is strongly associated with MALT
 

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Depressed immunity - such as caused by immune-suppressing drugs used to prevent
rejection of organ transplants. 

Lay comment It may be that depressed immunity is a common underlying risk factor.  
For example, chemical exposures, increasing age, and chronic and viral infection may depress or modify immunity in ways that favor the development of a lymphoma.
 

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Family history - genes and/or shared environmental determinants are associated with increased risk
 

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Genotypes - normal genetic variations that regulate immunity or cellular defense mechanisms 
may predispose some individuals to developing a lymphomas or other cancers.
 

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Viral exposures - Epstein Barr, Hepatitis C, and SV-40 are associated with some kinds of lymphomas.
 

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Age  - increasing age is a known risk factor for developing lymphomas and other cancers.
The median age for the development of NHL is about 65 years. 
 

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Chance - so-called copy errors can take place within cells when they divide, leading to 
abnormal growth and survival controls of the cells.  Such chance errors may become more 
common, or inadequately addressed by repair mechanisms, when combined with factors listed above.

"It is likely that most blood cancers are the result of cellular misadventures in blood-forming cells 
or lymphocytes, aberrations of normal cell processes, such as spontaneous mutations 
resulting in oncogene formation and inadequacies of DNA repair mechanisms."  http://theoncologist.alphamedpress.org/cgi/content/full/13/2/126 

NOTES: It's difficult to identify factors that may cause lymphoma, and
many of the items within are classified as associations, and not as validated risk factors. 

An association is an observation that one event or condition occurs more commonly with another. But associations do not mean one thing caused another. See also Associations 

A cancer occurs when cells develop mutations that lead to loss of growth and survival controls - leading to so-called malignant behavior of that cell and all of its descendents.  It should be noted that avoidance of risk factors after the fact (following a diagnosis) will not undo or reverse the genetic defects in cancer cells... no more than putting away a match will put out a previously set fire.

What caused My Lymphoma?

There's a strong consensus that the development of a lymphoma is the result of many factors over a very long period of time - and not one cause.

That is, for a normal lymphocyte to become a lymphoma requires multiple mutations to key genes (including so-called oncogenes) - such as to a gene that corrects cellular errors, or that initiates cell death when defects in the cell are detected, or to genes responsible for proliferation - that get stuck in the ON position.

You might imagine a single cell that by chance develops a mutation of a type that is not sufficient to initiate self-destruction ... perhaps it's a random error that can happen among the billions of cell divisions that take place in a day. (A chronic infection increasing the odds that copy error will occur during cell division.)

... This abnormal cell then divides and creates a family of atypical cells that are not yet malignant ... and, over time, only a handful continue on (perhaps stimulated to survive past their prime by infection?), which then acquire, by chance, or by exposure to chemicals or virus - another mutation ... and so on, and so on, for years.

(Years? Probably yes. Consider how long the latency is for melanoma, a skin cancer - presenting in adulthood but linked to sunburns in childhood. What accounts for the delay? Most likely, the requirement for additional mutations and damage to occur to specific genes within the sun-damaged cells.)

Also, as we age the built-in cellular and immune defenses against abnormal cells may weaken - an error "picked up" by our cells in our twenties is left unrepaired when we are sixty.

So ... age, chance, toxins, maybe in some cases a normal genetic predisposition, a chronic infection ... could all play a part in the path from normal lymphocyte to a lymphoma - defined as blood cells that has lost the ability to regulate their growth and survival.

So the question what caused my lymphoma seems impossible to determine in any single case - and it's proven elusive overall because there are multiple contributing factors - not the least of which are bad luck and aging. There are likely very different causes for any two survivors with the same diagnosis - a reason so many associations have been detected as suspected risk factors, but very few if any smoking guns.

~ Karl S.
 


Selected Resources: On the Causes of Lymphomas and other Cancers

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Battling the Hematological Malignancies: The 200 Years' War  theoncologist.alphamedpress.org
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Overview on causes of cancers Cancerhelp.org
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Infection-Driven Lymphomas:  The List Grows thehematologist 2004
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NIH 11th report on carcinogens  NIH.gov | Lymphoma-specific
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Update on Epidemiology and Therapeutics for Non-Hodgkin’s Lymphoma 
Julie M. Vose, Brian C.-H. Chiu, Bruce D. Cheson, Janet Dancey and John Wright  
(Posted Nov_28_02)  Abstract   asheducationbook.org
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Viral Origins of Lymphoma  MD Anderson Cancer Center
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Do you live in a high risk area?  MAP on NCI website
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Occupation and risk of non-Hodgkin's lymphoma and chronic lymphocytic leukemia. 
J Occup Environ Med. 2002 May;44(5):469-74. PMID: 12024692 PubMed abstract
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Risk factors, overviews  MSKCC  
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Roswell Park Cancer Institute  Journal updates
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Some aspects of the etiology of non-Hodgkin's lymphoma NIH.gov

Allergies

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Allergies and risk of non-Hodgkin's lymphoma by subtype. Cancer Epidemiol Biomarkers Prev. 2002 Apr;11(4):401-7. PMID: 11927501  PubMed
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Case-control study of non-Hodgkin's lymphoma among women and heterosexual men in the San Francisco Bay Area, California. Am J Epidemiol. 1999 Aug 15;150(4):375-89. PMID: 10453814  PubMed

Aspirin

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Regular use of aspirin or acetaminophen and risk of non-Hodgkin lymphoma. http://www.ncbi.nlm.nih.gov/pubmed/15947882  2005 Apr;16(3):301-8.
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Regular use of aspirin, but not other nonsteroidal anti-inflammatory drugs (NSAIDs), is associated with a significant reduction in risk of Hodgkin's lymphoma  docguide.com
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Aspirin may help prevent Hodgkin's disease- study 18 Feb 2004  cnn.com

Autoimmune
disease

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Autoimmune Disease Is a Risk Factor for the Development of Non-Hodgkin's Lymphoma  rheum.com

Bacteria
H pylori risk

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Clear association has been made, and treatment of H pylori can resolve the MALT lymphoma.

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Regression of gastric high grade MALT lymphoma after Helicobacter pylori eradication

Benzene

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"Exposure to benzene, an important industrial chemical and component of 
gasoline, is a widely recognized cause of leukemia, but its association with 
non-Hodgkin lymphoma (NHL) is less clear."

full text: http://cebp.aacrjournals.org/cgi/content/full/16/3/385 

"Potential mechanisms include immunotoxicity and the induction of
double-strand breaks with subsequent chromosome damage resulting in
translocations and deletions. We conclude that, overall, the evidence
supports an association between occupational benzene exposure and NHL."

Blood
transfusions

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"The findings in this study suggest that occupational exposure to specific chemicals plays an important role in the development of NHL in Canada."

Chemicals 
(PCBs), 
associations

(occupational)

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"The findings in this study suggest that occupational exposure to specific chemicals plays an important role in the development of NHL in Canada."

Comment:  The evidence regarding the causal effects of herbicides and pesticides in lymphomas appears thin (even if plausible).  However,  I found the precautionary principle described in the report below to be very compelling ... and grounded in common sense. ~ KarlS

The Dose Makes the Poison—Or Does It?

INVOKING THE PRECAUTIONARY PRINCIPLE

You may have heard of the Precautionary Principle, an approach that developed in Europe to protect human health and the environment in the face of the many unanswered and answerable questions related to environmental and human health. The principle calls for implementation of preventative measures to protect environmental quality and public health in spite of scientific uncertainties.

 www.actionbioscience.org
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Understanding Population and Individual Risk Assessment: The Case of Polychlorinated Biphenyls and Lymphoma cebp.aacrjournals.org

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A Cross-Sectional Study of Occupational Exposure to Trichloroethylene (TCE), Chromosomal Aberrations, and Related Biomarkers in Guangdong, China  ClinicalTrials.gov  

Comment:  We are often asked if it would be useful to poll support list members to help identify common life style factors and exposures that may have led to developing lymphomas. 

It's very  difficult to find reliable answers to questions like this by using surveys because there are just too many factors to consider, and it's virtually impossible to quantify the exposures  (concentrations, time, confounding factors) ... many of which can happen without our knowledge.  Do we know, for example, what's in our drinking water, air, and foods?

For this reason, epidemiologists focus research on occupational groups so that the exposures of suspected agents can be more reliably estimated. But even with this approach there have been many suspects identified, but no conclusive information. Nobody to prosecute and lock up.

But, an important new investigational tool may help cement causal environmental factors that lead to increased risk of lymphomas. In the study below, molecular profiling will be done on persons exposed to TCE in the workplace who have developed a lymphoma, and who have not yet received treatment. With this tool it may be possible to identify specific "chromosomal aberrations that have been associated with NHL and related hematological malignancies."

It's one thing to say you have lymphoma and you were exposed to TCE, and another to say: TCE is known to cause specific chromosome damage to lymphocytes in animals and people. These individuals have lymphoma, were exposed to significant levels of TCE, and the malignant cells have this specific abnormality.

If the study determines this, we will have a much higher level of confidence about the risk of TCE specific to lymphoma ... a smoking gun - a biomarker. The link above describes a study with this goal that is recruiting patients. It's an NCI study. The center is in Maryland.
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Persistent organochlorine (PCB) chemicals in plasma and risk of non-Hodgkin's lymphoma. Cancer Res. 2005 Dec 1;65(23):11214-26. PMID: 16322272 | Related articles
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PCBs, furans may factor in risk of non-Hodgkin lymphoma  eurekalert.org

Scientists have found some additional evidence that environmental exposure to polychlorinated biphenyls (PCBs) may be associated with non-Hodgkin lymphoma, according to a study published in the December 1 issue of Cancer Research.
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Report Supports Association Between Agent Orange and CLL
  
"A re-evaluation of evidence now supports an association between exposure to herbicides used during the Vietnam War and the development of a specific form of leukemia in veterans"  IOM  protectingourhealth.org
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Blood Levels of Organochlorines before and after Chemotherapy among Non-Hodgkin’s Lymphoma Patients  cebp.aacrjournals.org
 
" Several small studies suggest a link between environmental exposure to organochlorine compounds and risk of non Hodgkin’s lymphoma (NHL). Because NHL is uncommon, studies of the topic often use a population-based case-control design, in which cases generally are enrolled after treatment has begun.  If chemotherapy affects blood levels of organochlorines, exposure will be misclassified and findings distorted. "
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Case-control study on concentrations of organohalogen compounds and titers of antibodies to Epstein-Barr virus antigens in the etiology of non-Hodgkin lymphoma   safe2use.com
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A nested case-control study of non-Hodgkin lymphoma and serum organochlorine residues.
Lancet. 1997 Jul 26;350(9073):240-4. PMID: 9242800  PubMed
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NHL and occupational exposure to chemicals in Canada. Canadian Cancer Registries Epidemiology Research Group  PubMed

Diet and risk of lymphoma

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Diet and nutrient intakes and risk of non-Hodgkin's lymphoma in Connecticut women.
Am J Epidemiol. 2004 Mar 1;159(5):454-66. PMID: 14977641 

Risk of NHL associated with diet and nutrient intakes appeared to vary based on NHL subtype. An association between dietary intake and NHL risk is biologically plausible because diets high in protein and fat may lead to altered immunocompetence, resulting in an increased risk of NHL. The antioxidant or inhibiting nitrosation reaction properties of vegetables and fruits may result in a reduced risk.
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Obesity and risk of non-Hodgkin's lymphoma: A meta-analysis.
Int J Cancer. 2007 Apr 18;  PMID: 17443495 

These findings indicate that excess body weight is associated with an increased risk of non-Hodgkin's lymphoma, especially of diffuse large B-cell lymphoma.

Dioxin exposures Return to top

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Understanding Population and Individual Risk Assessment: The Case of Polychlorinated Biphenyls and Lymphoma http://cebp.aacrjournals.org/content/15/5/830.full 
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Dioxin emissions from a solid waste incinerator and risk of non-Hodgkin lymphoma. Epidemiology. 2003 Jul;14(4):392-8. PMID: 12843761 | Abstracts

Drugs

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There have been reported associations between certain drugs and an increased risk of developing a lymphoma. 

TOPIC SEARCH: PubMed

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Association of chronic inflammation, not its treatment, with increased lymphoma risk in rheumatoid arthritis. Arthritis Rheum. 2006 Mar;54(3):692-701. PMID: 16508929 
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Should arthritis patients fear the side effects of Enbrel, Remicade, and Humira? about.com    
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Remission of lymphoma after drug withdrawal in rheumatoid arthritis  eMJA
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Lymphoma in patients with rheumatoid arthritis: what is the evidence of a link with methotrexate? Drug Saf. 1999 Jun;20(6):475-87. Review. PMID: 10392665  PubMed

Familial or Genes and risk of developing lymphomas

Familial describes a trait or disease that is observed with higher frequency
within the same family, whether the etiology [cause] is genetic or environmental, or a combination of the two.  Where a hereditary disease is one that is caused by a genetic trait.

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TOPIC SEARCH: PubMed | Medscape | Web

"The risk of lymphoma among siblings of lymphoma probands (family members through whom a family's medical history comes to light.) was over 2.5-fold that of the general population and lower among other family members." [1]  

However, common environmental exposures have not been ruled out: "Lymphomas may also cluster within families, not because of an inherited genetic susceptibility, but because of shared environmental determinants." B. Cheson  asheducationbook.org

  1. The incidence of lymphoma in first-degree relatives of patients with Hodgkin disease and non-Hodgkin lymphoma: results and limitations of a registry-linked study. Cancer. 2000 May 15;88(10):2357-66. PMID: 10820359  PubMed
  2. Familial aggregation of hematopoietic malignancies and risk of non-Hodgkin's lymphoma.
    Cancer Res. 1992 Oct 1;52(19 Suppl):5468s-5473s. Review. PMID: 1394155  PubMed
  3. The development of lymphomas in families with autoimmune lymphoproliferative syndrome with germline Fas mutations and defective lymphocyte apoptosis. Blood. 2001 Jul 1;98(1):194-200. PMID: 11418480  PubMed
  4. CLL: Scientists find new leukemia gene risk factors http://bit.ly/7zIA4W
     
  • Risk of Non-Hodgkin's Lymphoma and Family History of Lymphatic, Hematologic, and Other Cancers - Vol. 13, 1415-1421, September 2004   aacrjournals.org
  • The role of genes in the development of non-Hodgkin's lymphoma  news-medical.net 

    "... variations of individual DNA building blocks in genes encoding for the cellular signaling molecules tumor necrosis factor (TNF) and interleukin 10 (IL-10) increase the risk of developing non-Hodgkin's lymphoma."
  • Familial risk for non-Hodgkin lymphoma and other lymphoproliferative malignancies by histopathologic subtype: the Swedish Family-Cancer Database  bloodjournal.org/cgi/content/full/106/2/668  Blood, 15 July 2005, Vol. 106, No. 2, pp. 668-672.

    "The present findings give evidence for a strong familial association of NHL, with little differences in the magnitude of risks for various histopathologic subtypes. The patterns of risks in parents and siblings support the hypothesis of an autosomal-dominant component for diffuse large B-cell NHL and a recessive one for follicular NHL."
  • Anticipation in families with Hodgkin's and non-Hodgkin's lymphoma in their pedigree.
    Leuk Lymphoma. 2006 Oct;47(10):2115-27. PMID: 17071485 

    "Anticipation" is an earlier onset and/or increasing severity [of disease] in successive generations.  ... These data suggest that anticipation occurs in families that exhibit both HL and NHL and that both neoplasms may have a common genetic basis.
  • Family history of hematopoietic cancer increases non-Hodgkin lymphoma risk  cancerpage.com  2007

    "Because family history represents the interaction between shared environmental exposures, behaviors, and genetic susceptibility, a full understanding of NHL heritability can provide clues regarding underlying disease mechanisms, particularly as it relates to disease and subtype-specific heterogeneity," the investigators explain.

    "Future efforts in sib-pair or twin studies may further our understanding of the sibling relationships, particularly for the male- and female-specific associations for family history of NHL and leukemia, respectively," the researchers add.
  • Highly increased familial risks for specific lymphoma subtypes. 
    Goldin LR, Björkholm M, Kristinsson SY, Turesson I, Landgren O. Br J Haematol. 2009 May 4. PMID: 19438470

    Relatives were at the highest risk for developing the same lymphoma subtype as the case. DLBCL was increased 10-fold among relatives of DLBCL patients, FL was increased fourfold among relatives of FL patients and HL was increased fourfold among relatives of HL patients. These results imply that germline susceptibility genes are specific to lymphoma subtype.
  • ... Genetic Susceptibilities

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    Polymorphisms are normal genetic variations that influence biological processes ... each variation may have both strengths (protective aspects) and weaknesses (susceptibilities). Just as being tall or short can provide advantages and disadvantages.

    We already know that normal genetic variations are what account for differences in how patients metabolize the same drugs, just one example - but also data is emerging that polymorphisms influence susceptibility to disease.

    Get used to seeing polymorphisms in the news, and SNP, pronounced "snips," which stands for Single Strand Polymorphisms.

    Polymorphisms may explain why persons exposed to the same toxins do not all come down with cancers. But susceptibility does not mean causing ... for example, other  triggers may be required, such as environmental exposures.

    (KS 2/08)

    bullet See SNPs fact sheet ornl.gov

    News Items

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    NEW Gene linked to increasingly common follicular lymphoma eurekalert.org/ 

    Dr. Brown said individuals who had the A variant were nearly twice as likely to develop follicular lymphoma. ... To reduce the potential for complicating factors, the more than 3,000 samples in the UC Berkeley-TGen study were from individuals who were HIV negative.
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     A functional TNFRSF5 gene variant is associated with risk of lymphoma. Blood. 2008 Feb 20; PMID: 18287517  

    These results suggest that the TNFRSF5 -1C>T polymorphism may increase FL susceptibility through mechanisms that hinder cellular immune responses. Further studies are needed to explore these findings.
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    Cytokine polymorphisms in the Th1/Th2 pathway and susceptibility to non-Hodgkin lymphoma. Blood. 2006 Jan 31;  PMID: 16449530 | Related articles | SNPs Fact Sheet NIH
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    Immune Mechanisms in Non–Hodgkin Lymphoma: Joint Effects of the TNF G308A and IL10 T3575A Polymorphisms with Non–Hodgkin Lymphoma Risk Factors Abstract  

    These exploratory results require replication but provide evidence that autoimmune conditions, late birth order, and obesity act partly through a common inflammatory pathway, posing a greater risk to individuals with variant TNF and IL10 genotypes than those with wild-type alleles.
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    Genetic Susceptibility to Lymphoma - Technical review ncbi.nlm.nih.gov

    Fats
    (saturated, trans)
    and some meats

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    TOPIC SEARCH: PubMed 

    "Intake of beef, pork, or lamb as a main dish was associated with a statistically significantly increased risk of NHL. Higher intake of trans unsaturated fat was also statistically significantly associated with an increased risk of the disease." [1]

    1. Dietary fat and protein in relation to risk of NHL among women  - Full Text
    2. Diet and risk of non-Hodgkin lymphoma in older women.
      JAMA. 1996 May 1;275(17):1315-21. PMID: 8614116 | Related articles
    3. Dietary factors and non-Hodgkin's lymphoma in Nebraska (United States).
      Cancer Causes Control. 1994 Sep;5(5):422-32. PMID: 799996

    Fluoride

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    "The percentage of people supplied with "optimally" fluoridated drinking water (FD) obtained from the Fluoridation Census 1985, U.S.A. were used for regression analysis of incidence rates of cancers at thirty six sites (ICD-WHO, 1957)." [1]

    1. Regression analysis of cancer incidence rates and water fluoride in the U.S.A. based on IACR/IARC (WHO) data (1978-1992). International Agency for Research on Cancer.
      J Epidemiol. 2001 Jul;11(4):170-9. PMID: 11512573  PubMed
    2. Correlation of incidence rates for selected cancers in 29 census sub-divisions of Alberta, Canada, 1961-1981. Ecol Dis. 1983;2(2):129-33. PMID: 6332009  PubMed

    Life Style 
    Sunlight / Diet

    Also see Fats

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    "Higher intake of vegetables, particularly cruciferous vegetables, may reduce the risk of non-Hodgkin's lymphoma among women." [1]

    1. Higher intake of fruits and vegetables associated with lower risk of NHL  Harvard.edu 
    2. Gene-nutrient interactions among determinants of folate and one-carbon metabolism on the risk of non-Hodgkin lymphoma: NCI-SEER Case-Control Study. Blood. 2006 Nov 21;  PMID: 17119116 

      lower risk of non-Hodgkin lymphoma (NHL) associated with high consumption of vitamin B6 and methionine, dietary determinants of one-carbon metabolism.
    3. Sun exposure, vitamin D receptor gene polymorphisms and risk of non-Hodgkin lymphoma. Abstract

      "Recent findings suggest that ultraviolet (UV) radiation exposure may reduce risk of developing non-Hodgkin lymphoma (NHL), but the biologic basis for this relationship remains unclear."
    4. Green tea consumption and hematologic malignancies in Japan: the Ohsaki study

    Gasoline exposure and associated risk

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    • Occupational Exposures and Non-Hodgkin’s Lymphoma in Southern Sweden  PDF

      Eric Dryver, MD, Lars Brandt, MD, PHD, Timo Kauppinen, PHD, Hakan Olsson, MD, PHD

      "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."

      See for meaning of OR 

    Hair Dye

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    ... experimental animal studies and other epidemiologic studies provides little convincing evidence linking non-Hodgkin's lymphoma with normal use of hair-color products in humans." [1]
    1. Hair-color products and risk for non-Hodgkin's lymphoma: a population-based study in the San Francisco bay area. Am J Public Health. 1998 Dec;88(12):1767-73. PMID: 9842372  PubMed

    Hormone Replacement Therapy

     

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    For menopausal hormone therapy use, overall associations between NHL and unopposed estrogen and estrogen plus progestin were null, with the potential exception of an inverse association (RR = 0.49, 95% CI, 0.25-0.96) between use of unopposed estrogen and diffuse large B-cell lymphoma (DLBCL), the most common NHL subtype, among women with a hysterectomy. These data do not support an important role for reproductive factors or exogenous hormones in modulating lymphomagenesis. 2
     
    1. Hormone Replacement Therapy and Risk of Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia1 PuMed  | full text
    2. Reproductive factors, exogenous hormone use and risk of lymphoid neoplasms among women in the National Institutes of Health-AARP Diet and Health Study Cohort. http://bit.ly/1gEc3z  

      n -= 134,074 women.

    Magnetic Fields

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    "Lymphoma Promotion Studies -- Studies conducted in two strains of transgenic mice [PIM mice carrying the pim-1 oncogene and TSG-p53 mice, in which the tumor suppressor gene, p53, has been deleted] revealed no activity of 60 Hz magnetic field exposure as a promoter of hematopoieticneoplasia." [1]
     
    1. Studies to Evaluate the Toxicity and Potential Carcinogenicity of 60 Hz Magnetic Fields in Laboratory Animals  infoventures.com

    Melanoma

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    It is prudent to check for melanoma often if you have NHL.

    An association between cutaneous melanoma and non-Hodgkin's lymphoma: pooled analysis of published data with a review oxfordjournals
    1. See for more detail and ABCD image chart 

     Metals

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    1. Listing Occupational Carcinogens
      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1247606/?tool=pmcentrez
       
    2. Genetic and Epigenetic Mechanisms in Metal Carcinogenesis and
      Cocarcinogenesis: Nickel, Arsenic and Chromium
      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2602826/?tool=pmcentrez

    Mothballs

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    1. Mothballs linked to increase risk of lymphoma in women  ehp.niehs.nih.gov | abstract

    Nitrates in
    drinking water

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    "These findings indicate that long-term exposure to elevated nitrate levels in drinking water may contribute to the risk of NHL." [1]

    1. Drinking water nitrate and the risk of non-Hodgkin's lymphoma - NCI

    Immune suppression/Organ Transplants/HIV/AIDS

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    A depressed or malfunctioning immune system is associated with increased risk of developing Lymphomas.
     
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    Meta-analysis of risk for lymphoma with immunomodulators for inflammatory bowel disease  http://bit.ly/aFd4kp
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    Risk of Lymphoma Following Exposure to Calcineurin Inhibitors and Topical Steroids in Patients with Atopic Dermatitis. J Invest Dermatol. 2006 Nov 9;  PMID: 17096020 
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    Cancer risk from arthritis drugs overstated-study  alertnet.org 

    The new analysis showed the cancer risk was 2.4 times greater among patients who used the drugs, and the risk of infectious disease was 1.8 times greater.
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    Immunomodulators for Inflammatory Bowel Disease Raise Lymphoma Risk  oncolink

    "Treating inflammatory bowel disease (IBD) with azathioprine or 6-mercaptopurine (6-MP) increases the risk of lymphoma by about fourfold, according to a report in the August issue of Gut. Still, the absolute risk of this malignancy is small and, for most patients, the benefits of these agents outweigh the risks."
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    Primary Immune Deficiency (Hyper-IgM Syndrome)  Immune Deficiency Foundation
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    Lymphoma risks in populations with altered immunity--a search for mechanism.  Cancer Res 1992 Oct 1;52
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    HIV/AIDS: Update: cancer risk in persons with HIV/AIDS in the era of combination antiretroviral therapy.  AIDS Read 2000 Jun;10(6):341-6
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    The role of immunosuppression in lymphoma.  Recent Results Cancer Res 2002;159:55-66

    Pesticides

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    bullet
    Pesticides Research Report: Do Pesticides Cause Lymphoma?
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    A nested case-control study of non-Hodgkin lymphoma and serum organochlorine residues.
    Lancet. 1997 Jul 26;350(9073):240-4. PMID: 9242800  PubMed
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    Pesticides and childhood lymphoma: "A newly published study has found that children exposed to pesticides in the home may be three to seven times more likely to develop non-Hodgkin's lymphoma (NHL), compared to unexposed children." article - CNN  abstract - Cancer 2000 Dec 1;89(11):2315-21
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    Published studies showing pesticides increase risk:
    Cancer Epidemiol Biomarkers Prev 2001 Nov;10(11):1155-63
    Cancer 1999 Mar 15;85(6):1353-60
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    Environmental epidemiology of non-Hodgkin's lymphoma in eastern Nebraska.  Am J Ind Med 1990;18(3):303-5

    Rheumatoid Arthritis

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    "Disease processes at work in patients with rheumatoid arthritis appear to increase their risk of developing lymphoma, a form of cancer that affects lymph tissue, according to Swedish researchers."

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    Incidence of lymphoma in patients with rheumatoid arthritis: a systematic review of the literature.

    http://www.ncbi.nlm.nih.gov/pubmed/18501101 
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    Should arthritis patients fear the side effects of Enbrel, Remicade, and Humira? about.com  
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    Remission of lymphoma after drug withdrawal in rheumatoid arthritis  eMJA
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    Lymphoma in patients with rheumatoid arthritis: what is the evidence of a link with methotrexate? Drug Saf. 1999 Jun;20(6):475-87. Review. PMID: 10392665  PubMed
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    Rheumatoid Arthritis & Lymphoma  PersonalMD.com

    Psoriasis

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    Patients with psoriasis are at increased risk for developing lymphoma. But additional studies are necessary to determine if the increased rate of lymphoma is related to psoriasis severity, psoriasis treatment, or an interaction between these risk factors. 
     
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    Lymphoma Rates Are Low but Increased in Patients With Psoriasis: Results From a Population-Based Cohort Study in the United Kingdom. 
    Arch Dermatol. 2003 Nov;139(11):1425-1429.  PMID: 14623702 | Related abstracts
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    Researchers Link Psoriasis to Increased Lymphoma Rate  psoriasis.org 

    They also commented that it is not clear whether the increased rate was due to psoriasis severity or treatment, or whether the results apply to younger patients.

    Sjogren’s
    Syndrome

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    Malignant lymphoma in primary Sjogren's syndrome.  Isr Med Assoc J 2001 Oct;3(10):761-6

    "A low grade marginal-zone lymphoma related to mucosa-associated lymphoid tissue is the commonest lymphoid neoplasia in Sjogren's syndrome."
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    See Sjögren's Syndrome for details about this condition and its associations with lymphomas.

    Smoking

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    Expression of DNA mismatch repair proteins in transformed non-Hodgkin's lymphoma: Relationship to smoking. Leuk Lymphoma. 2006 Sep;47(9):1806-12. PMID: 17064992 

    We found that the relative risk of negative immunostaining for either MLH1 or MSH2 was 2.2 times higher in smokers than non-smokers (relative risk = 2.2041, 95% confidence interval: 0.89714, 5.41491). No direct correlation was found between smoking and the mutations in the p53 gene. These results suggest that cigarette smoking may play a role in the development of transformed lymphomas through defective mismatch repair.
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    Tobacco and alcohol consumption and risk of lymphoma: Results of a population-based case-control study in Germany. Int J Cancer. 2005 Aug 3; PMID: 16080191 
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    Italian Study Links Tobacco Use to Development of [follicular] Non-Hodgkin’s Lymphoma  cancerconsultants.com 
     
    "They reported a 50 percent increased risk for 16-33 pack-years and an 80 percent increased risk with 34 pack years or greater. There was no increased risk for the other NHL subtypes. In the second study, data on over 6,500 cases of NHL showed only an increase incidence of follicular NHL and not other cell types."
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    Smoking AND lymphoma  Related PubMed abstracts
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    Cigarette Smoking in Women Increases Risk for Follicular Lymphoma.
    United States Researchers from Yale University have reported that long-term cigarette smoking in women increases the risk of developing follicular lymphoma.  cancerconsultants.com

    Stress?

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    Because stress is such a common part of life it's exceedingly difficult if not impossible to measure objectively, or to link it to this or any disease conclusively.

    Stress could play a role in immune suppression, so I think epidemiologists have looked for extreme cases of stress - loss of a child, divorce, etc., to see if there's an increased incidence of lymphoma in such populations.

    See for one report: http://bit.ly/6Z50M4 but note that confounders exist, such as possible shared genetic determinants and environmental exposures (ie., virus/other), and that the increased risk is small - as in not definitive - could be from unrelated factors.

    Most experts say that the development of any cancer is not determined by one, but by multiple factors and that for a normal cell to become a cancer requires multiple "hits" on DNA within the cell. So even if stress plays a small part in some cases, it's probably not the main player.

    KarlS

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    Query "psychological stress" AND risk of lymphoma? PubMed 
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    Stressful life experiences and risk of relapse of breast cancer: observational cohort study  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC115851/
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    Cancer survival in parents who lost a child: a nationwide study in Denmark  http://www.nature.com/bjc/journal/v88/n11/full/6600948a.html
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    Stress spectrum disorders in oncology ncbi.nlm.nih.gov
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    Psychological stress in oncology: the role of glucocorticoids - ncbi.nlm.nih.gov
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    Neuroendocrine-immune mechanisms of behavioral comorbidities in patients with cancer. ncbi.nlm.nih.gov

    SV40 virus

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    Caption; Toronto Star, March 8, 2002, SECTION: LIFE; Pg. LI04

    "SIMIAN LINK: The simian virus 40 has been found in 42 per cent of non-Hodgkin's lymphoma samples. This could shed new light on the origins of these blood cancers that have become more common over the last 30 years, reports The Lancet. SV40 usually infects rhesus monkeys. In the 1950s and early '60s, millions of people were given a polio vaccine accidentally infected with the virus. But some patients with SV40-infected tumors were born after 1963 and would not have been exposed to the contaminated vaccine. Researchers conclude that SV40 continues to spread among humans in ways that are not clear."

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    See SV40 Issues for recent updates details.
    Viral
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    "Accumulating evidence support a role for hepatitis C virus (HCV) in the pathogenesis of human lymphoproliferative disorders." 
     

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    Treatment of Hepatitis C Reduces Incidence of Non-Hodgkin’s Lymphoma cancerconsultants.com

    Researchers from Japan have reported that viral elimination in hepatitis C virus (HCV) infected patients reduces the incidence of non-Hodgkin’s lymphoma (NHL). The details of this study appeared in the December, 2007 issue of the American Journal of Medicine.
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    Hepatitis C infection increases lymphoma risk   aidsmap.com

    "Although the risk of developing lymphomas is small, our research suggests that screening of HCV-infected individuals could identify conditions which may lead to cancer. It might then be possible to prevent progression to lymphoma," commented investigator Eric A. Engels, adding, "more research is needed to further clarify the relationship between HCV infection and lymphoma."
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    The lymphoid system in hepatitis C virus infection: autoimmunity, mixed cryoglobulinemia, and Overt B-cell malignancy. Semin Liver Dis. 2000;20(2):143-57. Review. PMID: 10946420 

    It can be postulated that HCV is the stimulus not only for the apparent benign lymphoproliferative process underlying a wide spectrum of clinical features, but also for the progression to frank lymphoid malignancy in a subgroup of patients. Current data indicate a higher prevalence of overt B-cell non-Hodgkin's lymphoma in HCV-infected patients, especially in some geographic areas.
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    Hepatitis C virus infection and non-hodgkin lymphoma: Results of the NCI-seer multi-center case-control study. Int J Cancer. 2004 Aug 10;111(1):76-80. PMID: 15185346 | Related Articles
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    Epstein-Barr virus (EBV) associated lymphomas  Related abstracts
    The three main types of EBV-associated B-cell lymphoma are Burkitt lymphoma, Hodgkin lymphoma and post-transplant lymphomas.
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    Case-control study on concentrations of organohalogen compounds and titers of antibodies to Epstein-Barr virus antigens in the etiology of non-Hodgkin lymphoma   safe2use.com 
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    Hepatitis C virus, B-cell proliferation and lymphomas.
    Leuk Lymphoma. 2002 Apr;43(4):747-51. PMID: 12153160  PubMed
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    Viral Origins of Lymphoma  MD Anderson Oncology
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    Association between hepatitis C virus and NHL, and effects of viral infection on histologic subtype and clinical course
     
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