An investigation into modifiable causes of primary lymphoma of the digestive system: the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial
Principal Investigator
Name
Harindra Jayasekara
Degrees
MBBS MSc MD PhD
Institution
Cancer Council Victoria
Position Title
Principal Research Fellow
About this CDAS Project
Study
PLCO
(Learn more about this study)
Project ID
PLCO-1995
Initial CDAS Request Approval
Dec 5, 2025
Title
An investigation into modifiable causes of primary lymphoma of the digestive system: the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial
Summary
Background
Non-Hodgkin lymphoma (NHL) is the 10th most common type of cancer worldwide, and the 11th highest in terms of mortality.1 Extranodal lymphomas most commonly occur in the gastrointestinal (GI) tract; of these, more than half (~60-70%) involve the stomach, while others affect the small intestine (~20-30%) and colon (~10-20%).2,3 The two most common subtypes of GI lymphomas are diffuse large B-cell lymphoma (DLBCL), accounting for ~50% of GI lymphomas; and marginal zone lymphoma (MZL) of mucosa-associated lymphoid tissue (MALT), typically involving the stomach and accounting for ~20%.2
Risk factors common to most types of GI lymphomas include immunosuppression, autoimmunity, and certain viral infections (e.g. Hepatitis B/C, Epstein-Barr virus [EBV]).2-6 Specific to gastric MALT lymphoma is the link to Helicobacter pylori infection.2,3,6 The evidence is more mixed for involvement of lifestyle factors such as diet, smoking, and alcohol intake. Previous PLCO studies have only explored the relation of these lifestyle factors with NHLs in general (encompassing both GI and non-GI involvement).7
Aims
see separate section below
Study population
We plan to use PLCO data for this analysis.
Primary exposures
Our primary exposures are cigarette smoking, alcohol use, obesity, and processed meat/unprocessed red meat intake.
Outcome
Incident cases of GI lymphoma will be identified from ICD-O-3 codes specific to histopathological subtype, as standardised by InterLymph based on the 2008 WHO classification.8 Specific ICD-O-3 codes of interest include the following: diffuse large B-cell lymphoma (DLBCL) – 9680/3, 9684/3, 9688/3; extranodal marginal zone lymphoma (MZL) of mucosa-associated lymphoid tissue (MALT) – 9699/3 excluding site C77.0-77.9, including immunoproliferative small intestinal disease (IPSID) – 9764/3; enteropathy-associated T cell lymphoma (EATL) – 9717/3; peripheral T-cell lymphoma (PTCL) – 9702/3, 9675/3; mantle cell lymphoma (MCL) – 9673/3; and follicular lymphoma (FL) – 9690/3, 9691/3, 9695/3, 9698/3; among other rarer types.
Statistical analysis
Cox regression with age as the time axis will be performed to calculate hazard ratios (HRs) and 95% confidence intervals for NHL risk. Person-years of follow-up will be calculated from the date that the baseline questionnaire was received to the date that participants were diagnosed with the outcome of interest, died of any cause, moved out of a registry ascertainment area, were lost to contact tracing, or the end of the follow-up period. To test for heterogeneity in the HRs across subtypes of NHL, Cox regression models will be fit using a competing risks method.9 We will evaluate effect modification via models of continuous exposure.
References
1. Ferlay J, Ervik M, Lam F, et al. https://gco.iarc.who.int/today.
2. Olszewska-Szopa M, Wróbel T. Adv Clin Exp Med 2019;28(8):1119-1124.
3. Ghimire P, Wu GY, Zhu L. World J Gastroenterol 2011;17(6):697-707.
4. Luo J, Craver A, Bahl K, et al. J Natl Cancer Cent 2022;2(4):226-234.
5. Shirwaikar Thomas A, Schwartz M, Quigley E. BMJ Open Gastroenterol 2019;6(1):e000320.
6. Cerhan JR, Habermann TM. Ann Lymphoma 2021;5
7. Troy JD, Hartge P, Weissfeld JL, et al. Am J Epidemiol 2010;171(12):1270-81.
8. Turner JJ, Morton LM, Linet MS, et al. Blood 2010;116(20):e90-8.
9. Lunn M, McNeil D. International Biometric Society; 1995:524.
Aims
Objectives
i. To assess associations between lifestyle factors – namely, obesity as measured by body mass index (BMI); alcohol intake; tobacco smoking; and processed meat/unprocessed red meat intake – and risk of gastrointestinal (GI) lymphomas, adjusting for appropriate confounders
ii. To assess the above association, in relation to main subtypes of GI lymphomas as determined by histopathology (DLBCL, MALT, other), and if data are available, by differences in cell marker expression (e.g. CD10, CD20, and others) and/or genetics (germline variants or somatic translocations)
iii. To examine the above association stratifying for other biologically relevant variables (effect modifiers) including presence of Helicobacter pylori infection, autoimmune disease, and viral infection (EBV, HBV, HCV), if data are available
Collaborators
Harindra Jayasekara Cancer Council Victoria
Howard Tang Cancer Council Victoria
Roger Milne Cancer Council Victoria
Wen-Yi Huang NCI
Steven Moore NCI
Katherine McGlynn NCI