. Author manuscript; available in PMC: 2019 Jun 1.

Published in final edited form as: Gut. 2018 Feb 6;67(6):1168–1180. doi: 10.1136/gutjnl-2017-315537

Table 2.

Immunology–molecular pathological epidemiology (MPE) studies on possible aetiological factors and incidence of neoplasia subgroups classified by immune response to tumour

First author, Year, ref	Study design	Cases with tissue specimens (sample size^*)	Study cohort	Exposure variables	Outcome variables	Main findings on exposures and risk of disease subtypes classified by local tissue immune status
Cao 2016²⁸⁹	Prospective cohort study	Colorectal cancer (1458 cases in 1 34 981 participants)	Health Professionals Follow-up Study and Nurses’ Health Study	Aspirin use	Incidence of colorectal cancer subtype classified by lymphocytic infiltrates	Regular aspirin use is associated with lower incidence of colorectal cancer subtype with lower level tumour-infiltrating lymphocytes (TIL) but not that of subtype with higher level TIL.
Hanyuda 2016²⁹⁰	Prospective cohort study	Colorectal cancer (1436 cases during 3 346 000 person-years of follow-up)	Health Professionals Follow-up Study and Nurses’ Health Study	Body mass index (BMI)	Incidence of colorectal cancer subtype classified by lymphocytic infiltrates	BMI is not associated differentially with risk of colorectal cancer subtypes classified by lymphocytic infiltrates.
Khalili 2015²²¹	Nested case-control study within prospective cohort study (subgroup analysis in consortium)	Colorectal cancer (288 cases and 1172 controls)	Health Professionals Follow-up Study and Nurses’ Health Study (in Genetics and Epidemiology of Colorectal Cancer Consortium)	Genetic polymorphism rs11676348 (risk allele for inflammatory bowel disease)	Incidence of colorectal cancer subtype classified by lymphocytic infiltrates	The rs11676348 C allele is associated with risk of colorectal cancer subtype showing Crohn’s-like lymphoid reaction but not risk of subtype showing no Crohn’s-like reaction.
Liu 2017²⁹¹	Prospective cohort study	Colorectal cancer (1311 cases in 1 24 433 participants)	Health Professionals Follow-up Study and Nurses’ Health Study	Dietary inflammatory index	Incidence of colorectal cancer subtype classified by lymphocytic infiltrates	Inflammatory diet is associated with higher incidence of colorectal cancer subtype with lower level intratumour periglandular reaction but not that of subtype with higher level reaction.
Song 2016²²³	Nested case-control study (within prospective cohort study)	Colorectal cancer (318 cases and 624 controls)	Health Professionals Follow-up Study and Nurses’ Health Study	25-Hydroxyvitamin D in plasma	Incidence of colorectal cancer subtype classified by lymphocytic infiltrates	Level of plasma 25-hydroxyvitamin D is associated with lower risk of colorectal cancer subtype with high-level tumour-infiltrating lymphocytes (TILs), but not with risk of subtype with low-level TILs.
Song 2016²²⁰	Prospective cohort study	Colorectal cancer (614 cases in 1 25 172 participants)	Health Professionals Follow-up Study and Nurses’ Health Study	Dietary intake of omega-3 polyunsaturated fatty acids (ω-3 PUFA)	Incidence of colorectal cancer subtype classified by lymphocytic infiltrates	Intake of ω-3 PUFA is associated with lower risk of colorectal cancer subtype with high tissue FOXP3⁺ cell density, but not with risk of subtype with low tissue FOXP3⁺ cell density.

Official symbols for genes and gene products including proteins are described in the HUGO Gene Nomenclature Committee (HGNC) website (www.genenames.org). Studies with <200 cases with tissue data are not listed.

Sample size is based on cases with available tissue data.