NCI: "Anything that increases your risk of getting a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesn't mean that you will not get cancer. Talk with your doctor if you think you may be at risk."  Continue to Overview below.
 

Overview

2013:  Experts on risk factors for acquiring lymphoma and how it's diagnosed  

There are many factors associated with the increased risk of developing a lymphoma, 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 what experts call the problem of confounding variables in epidemiological research.  For example, an elevated risk associated with exposure to a specific drug, may be from the drug, or from the underlying condition the drug is given to treat.  Environmental confounding variables are particularly complex as no two individuals breath the same air, have the same diets, drink the same water, or have exposures to the same infection or chemicals.   

There could be many contributing factors that lead to the development of a lymphoma over time, such as advancing age, chronic infection, inherited disposition, exposures to chemicals or radiation, and chance. 

"Anything that increases your risk of getting a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesn’t mean that you will not get cancer."    Cancer.gov

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

Regarding immune suppression as a risk factor?

Immune suppression is associated with an elevated risk of lymphoma – such as in transplant recipients where high doses of immune suppressing drugs on a daily basis are needed to prevent organ rejection.

Chronic inflammation (from autoimmune conditions) that are often treated with immune suppressing drugs (such as steroids) are also associated with increased risk of lymphoma – therefore, arguably, judicious use of anti-inflammatory drugs (steroids, NSAIDS) may decrease the net risk of lymphoma despite the association in people with autoimmune disease.

When the commercial says: “cases of lymphoma have been reported,” it does not mean that the drug caused it – only that the reported cases of lymphoma for those taking the drug appear to be higher than for the general population.

The factors that might have contributed to the lymphomas in this cohort include: chronic inflammation, shared predisposition to lymphoma and autoimmune disease, the long term use of steroids, or some other unknown factor.

In short, association is not evidence of causation.

An example: people who wear helmets when participating in sport have more brain injuries than the general population. Thus, helmets are associated with brain injury … But in this simple example it’s clear that the activity causes brain injury and that there would be more injuries in the sport without the helmet.

Regarding the risk of relapse – and just a lay person’s impression: Lymphomas take many years to present and multiple insults to the DNA are needed to cause it. It seems to me that the judicious use of steroids is very unlikely to increase the risk of lymphoma or of a relapse. More important would be the efficacy of the treatment for the lymphoma. Did it get all of the cells or not?

Full text reports:

	Science Daily: Type 2 Diabetes Linked to Increased Blood Cancer Risk
	Environmental Health News: Research links pesticides - The results strengthen an argument for an environmental link to increased risk for human NHL that is linked to higher levels of organochlorine pollutants.
	Epidemiology of adult non-Hodgkin lymphoma http://bit.ly/qdokmY
	Etiologic heterogeneity (risk factor variation) among NHL subtypes, Blood. 2008 http://bit.ly/bUDXZw
	Occupation and malignant lymphoma: a population based case control study in Germany, Occup Environ Med 2006 http://bit.ly/btSkWn
	Environmental and Occupational Causes of Cancer New Evidence, 2005–2007, Rev Environ Health 2009 http://bit.ly/afBT4S
	Patterns of autoimmunity and subsequent CLL in Nordic countries, Blood. 2006  http://bit.ly/d95BDm
	Inherited predisposition to CLL, http://bit.ly/a7dfp8 Expert Rev Hematol. 2008

Factors associated with an increase risk of developing a lymphoma:  

About Lymphoma > Risk Factors for Lymphoma Last update: 06/30/2017
TOPICS Overview | Allergies | Aspirin and other pain killers | Autoimmune Disease | Bacteria H pylori | Benzene | Blood Transfusions | Chemicals - Dioxin | Familial (inherited) Genetic | Fats | Fluoride | Gasoline | Hair Dye | Inflammation Hormone Replacement Therapy |  Immune Suppression | Life Style: Diet / Sunlight | Magnetic Fields | Melanoma | Metals | Mothballs | Nitrates | Pesticides | Psoriasis | Radon exposure | Rheumatoid Arthritis | Sjogren's | Smoking (tobacco) | Stress | Viral:  SV40 Virus | EBV | HCV | Mouse   TOPIC SEARCH: PubMed | SearchMedica What Caused My Lymphoma?
	Chemical exposures - chronic exposures to dioxins, PCBs, pesticides, solvents, and fertilizers
	Chronic infections - H pylori is strongly associated with MALT
	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.
	Family history - genes and/or shared environmental determinants are associated with increased risk
	Genotypes - normal genetic variations that regulate immunity or cellular defense mechanisms  may predispose some individuals to developing a lymphomas or other cancers.
	Viral exposures - Epstein Barr, Hepatitis C, and SV-40 are associated with some kinds of lymphomas.
	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.
	Chance - Genetic 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.

Related Items about risk factors ... in the News:

Not specific to lymphoma: Red meat cancer link explained | UTSanDiego http://bit.ly/1Bdkok0 when people consume beef, pork, lamb and bison, a sugar molecule called Neu5Gc from those meats gets fully incorporated into human tissue. The immune system then attacks that substance, leading to tissue inflammation and a higher lifetime risk of cancer. Most cancers are due to chance - random mutations.  However, about 1/3 are associated with environmental factors, such as smoking and diet.  This article very nicely explains an important research finding.  The study validated the role of a sugar molecule in meat, that finds its way into the cells of our body ... which can elicit an immune response leading to chronic inflammation, leading to an increased risk of cancer.  Source study: pnas.org A related article:  Most cancer is bad luck: Study | UTSanDiego http://bit.ly/14hH2LZ Source report: Bad Luck of Random Mutations Plays Predominant Role in Cancer, Study Shows - 01/01/2015 http://bit.ly/1DaNhg9

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 (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.
 

In the News:

	Medscape 2015: (free registration / login required) Does This Cause Cancer? http://bit.ly/1aLYxHk Experts discuss evidence for and against BPA, Cell Phones, Artificial Sweeteners, Pesticides, Power Lines ... then give interesting verdicts
	Geographic clustering for cutaneous t-cell lymphoma - PubMed - NCBI http://1.usa.gov/1F0MFMT

* Clin Gastroenterol Hepatol,  2014
Risks of Lymphoma with anti-tumor necrosis factor for IBD  http://1.usa.gov/1iEMJsN

* Leuk Lymph 2013:
Body mass index, height and risk of lymphoid neoplasms in a large United States cohort. http://1.usa.gov/1cL4uOl

* FHCRC 2013:
Study finds link between allergies and increased risk of blood cancers in women http://bit.ly/J2zxgT

* Medscape 2013:
Allergies and Hematologic Cancer Risk: Is There a Link? http://bit.ly/1eqN8ca

* Medical xpress 2013: Cancer:
Lymphoma-linked risk factor identified http://bit.ly/16IKPw2

* Cancer Research UK 2013:
Huge genetic analysis points to cancer-causing culprits http://bit.ly/1cDCTnL

Intriguing

* 2012, Shuangge , Associate Professor of Biostatistics, Yale University:
Risk factors for the etiology and prognosis of follicular lymphoma

Resources: On the Causes of Lymphomas and other Cancers

	Battling the Hematological Malignancies: The 200 Years' War  theoncologist.alphamedpress.org
	Overview on causes of cancers Cancerhelp.org
	Infection-Driven Lymphomas:  The List Grows thehematologist 2004
	NIH 11th report on carcinogens  NIH.gov | Lymphoma-specific
	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
	Viral Origins of Lymphoma  MD Anderson Cancer Center
	Do you live in a high risk area?  MAP on NCI website
	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
	Risk factors, overviews  MSKCC
	Roswell Park Cancer Institute  Journal updates
	Some aspects of the etiology of non-Hodgkin's lymphoma NIH.gov

Allergies

Aspirin and Other Pain Killers

Return to top

Autoimmune
disease

Return to top

Bacteria
H pylori risk

Return to top

Clear association has been made, and treatment of H pylori can lead to sustained remissions of H pylori + MALT lymphoma.

Regression of gastric high grade MALT lymphoma after Helicobacter pylori eradication

Benzene

Return to top

"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

Return to top

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

•  Blood Transfusion Is Independent Risk Factor For Women 

Chemicals 
(PCBs), 
associations

(occupational)

Return to top

"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

	Agent Orange - Fast Track for VA Claims
	Understanding Population and Individual Risk Assessment: The Case of Polychlorinated Biphenyls and Lymphoma cebp.aacrjournals.org
	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.
	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
	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.
	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
	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. "
	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
	A nested case-control study of non-Hodgkin lymphoma and serum organochlorine residues. Lancet. 1997 Jul 26;350(9073):240-4. PMID: 9242800  PubMed
	NHL and occupational exposure to chemicals in Canada. Canadian Cancer Registries Epidemiology Research Group  PubMed

Diet and risk of lymphoma

Return to top

Dioxin
exposures

Return to top

Drugs

Return to top

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

TOPIC SEARCH: PubMed

	Association of chronic inflammation, not its treatment, with increased lymphoma risk in rheumatoid arthritis. Arthritis Rheum. 2006 Mar;54(3):692-701. PMID: 16508929
	Should arthritis patients fear the side effects of Enbrel, Remicade, and Humira? about.com
	Remission of lymphoma after drug withdrawal in rheumatoid arthritis  eMJA
	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

Return to top

TOPIC SEARCH: PubMed | Medscape | Web

There may be inherited factors (susceptibilities) increasing the risk of developing a lymphoma, but a family history of lymphoma alone does not mean you have a high probability of developing a lymphoma.  It appears that other factors must contribute - including random copy errors (bad luck), chronic infection, increasing age, immune suppression, or common exposures to environmental toxins.   

New Item

Best Practice Res Clinical Haematol. 2011: Host genetics in follicular lymphoma http://1.usa.gov/XvKteN Given an estimated lifetime risk of NHL of 1 in 48 (2.1%) in the United States [1] and a RR of 1.5 for the risk of NHL in first degree family members [13], then the absolute lifetime risk of NHL is 3.2% in first degree relatives of an NHL patient. For FL, the estimated lifetime risk is 1 in 278 (0.36%) [1], and using a RR of 4.0 for the risk of FL in first degree family members [8], then the absolute lifetime risk of FL is 1.4% among first degree relatives of FL patients. The clinical significance of the absolute increased risk to relatives of patients with FL is not trivial, although the relatively low incidence of FL, the modest familial risk, and the lack of a screening test/clinical intervention all argue against clinical surveillance of families of FL patients at this time. Results of candidate gene studies of risk are too preliminary to move to the clinic, and even replicated loci are too few that they are not useful in identifying individuals at high risk of FL. Comment: regarding familial risks (incidence among relatives of patients with FL) shared environmental exposures cannot be ruled out as a contributing factor.

Genetic Susceptibility to Lymphoma - Technical review ncbi.nlm.nih.gov

"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  Source: 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
    

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

Return to top

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)

News Items

	Genetic Susceptibility to Lymphoma - Technical review ncbi.nlm.nih.gov
	See SNPs fact sheet ornl.gov

Fats
(saturated, trans)
and some meats

Return to top

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

Return to top

"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

Return to top

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

1. Incidence of hematologic malignancy and cause-specific mortality in the Women's Health Initiative randomized controlled trial of calcium and vitamin D supplementation - Ammann - 2017 - Cancer - Wiley Online Library http://bit.ly/2tto3y8
   
   In secondary analyses, protective associations were found to be most robust for lymphoid malignancies, with HRs of 0.77 (95% CI, 0.59-1.01) and 0.46 (95% CI, 0.24-0.89), respectively, for cancer incidence and mortality in those assigned to CaD supplementation.
    

2. Higher intake of fruits and vegetables associated with lower risk of NHL  Harvard.edu 

3. 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.

4. 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."

5. Green tea consumption and hematologic malignancies in Japan: the Ohsaki study

Gasoline exposure and associated risk

Return to top

Hair Dye

Return to top

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

Inflammation, chronic

 

Return to top

Hormone Replacement Therapy

Return to top

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

Return to top

1. Studies to Evaluate the Toxicity and Potential Carcinogenicity of 60 Hz Magnetic Fields in Laboratory Animals  infoventures.com
   

Melanoma

Return to top

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

Return to top

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

Return to top

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

Nitrates in
drinking water

Return to top

"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

Return to top

Pesticides

Return to top

Radon exposure

Return to top

Rheumatoid
Arthritis

Return to top

"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."

	Incidence of lymphoma in patients with rheumatoid arthritis: a systematic review of the literature. http://www.ncbi.nlm.nih.gov/pubmed/18501101
	Should arthritis patients fear the side effects of Enbrel, Remicade, and Humira? about.com
	Remission of lymphoma after drug withdrawal in rheumatoid arthritis  eMJA
	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
	Rheumatoid Arthritis & Lymphoma  PersonalMD.com

Psoriasis

Return to top

Sjogrens
Syndrome

Return to top

Smoking

Return to top

Stress?

Return to top

In the News

AACR: Risk of Infection-Related Cancers after the Loss of a Child: A Follow-up Study in Sweden http://bit.ly/V3BH2z

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

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

Viral
Associations

Return to top

EBV | HCV | Mouse virus | SV40 virus

A type of virus that can cause cancer (which are uncommon) is called an oncovirus: See for discussion: http://en.wikipedia.org/wiki/Oncovirus

Epstein Barr Virus (EBV)
 

About EBV - CVC

Epstein-Barr virus (EBV) associated lymphomas   Related abstracts

The three main types of EBV-associated lymphomas are

Burkitt lymphoma,
Hodgkin lymphoma and
post-transplant lymphomas
 

NEJM: Characteristics of Hodgkin's Lymphoma after Infectious Mononucleosis  nejm.org

snips:

"We estimated that the median incubation period for Hodgkin's lymphoma attributable to infectious mononucleosis–related EBV infection was 4.1 years, with a peak in risk 2.4 years after infection.

These estimates are in accordance with those of a large case–control study of Hodgkin's lymphoma in which the median interval between infectious mononucleosis and Hodgkin's lymphoma was five years.17

...

We emphasize that in absolute terms, the risk of Hodgkin's lymphoma after infectious mononucleosis is only on the order of 1 case per 1000 persons.5  Consequently, other cofactors acting in concert with infectious mononucleosis–related EBV infection presumably must be present for the infection to give rise to Hodgkin's lymphoma.16

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 

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.

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."

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.

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

Association between hepatitis C virus and NHL, and effects of viral infection on histologic subtype and clinical cours

Hepatitis C virus, B-cell proliferation and lymphomas.
Leuk Lymphoma. 2002 Apr;43(4):747-51. PMID: 12153160  PubMed

Viral Origins of Lymphoma  MD Anderson Oncology

Clonal Isolation of Different Strains of Mouse Mammary Tumor Virus-Like DNA Sequences from Both the Breast Tumors and NHL of Individual Patients Diagnosed with Both Malignancies
http://clincancerres.aacrjournals.org/content/10/17/5656.full

See SV40 Issues for recent updates and details.