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Second primary cancers in non-Hodgkin lymphoma : Bidirectional analyses suggesting role for immune dysfunction

Chattopadhyay, Subhayan LU ; Sud, Amit LU ; Zheng, Guoqiao LU ; Yu, Hongyao LU ; Sundquist, Kristina LU ; Sundquist, Jan LU ; Försti, Asta LU ; Houlston, Richard; Hemminki, Akseli and Hemminki, Kari LU (2018) In International Journal of Cancer 143(10). p.2449-2457
Abstract

Second primary cancers (SPCs) account for an increasing proportion of all cancer diagnoses. It is unlikely that prior therapy is solely responsible for SPC risk. To investigate risk of SPC after diagnosis of non-Hodgkin lymphoma (NHL) and 10 of its subtypes we conducted a novel bidirectional analysis, SPCs after NHL and NHL as SPC. Using the Swedish Family-Cancer Database, we identified 19,833 individuals with primary NHL diagnosed between 1993 and 2015. We calculated relative risks (RRs) of SPCs in NHL survivors and, for bi-directional analysis, risk of NHL as SPC. The overall RRs were significantly bidirectionally increased for NHL and 7 cancers. After diagnosis of NHL risks were increased for upper aerodigestive tract (RR = 1.96),... (More)

Second primary cancers (SPCs) account for an increasing proportion of all cancer diagnoses. It is unlikely that prior therapy is solely responsible for SPC risk. To investigate risk of SPC after diagnosis of non-Hodgkin lymphoma (NHL) and 10 of its subtypes we conducted a novel bidirectional analysis, SPCs after NHL and NHL as SPC. Using the Swedish Family-Cancer Database, we identified 19,833 individuals with primary NHL diagnosed between 1993 and 2015. We calculated relative risks (RRs) of SPCs in NHL survivors and, for bi-directional analysis, risk of NHL as SPC. The overall RRs were significantly bidirectionally increased for NHL and 7 cancers. After diagnosis of NHL risks were increased for upper aerodigestive tract (RR = 1.96), colorectal (1.35), kidney (3.10), bladder (1.54) and squamous cell skin cancer (SCC) (4.12), melanoma (1.98) and Hodgkin lymphoma (9.38). The concordance between RRs for each bidirectional association between NHL and 31 different cancers was highly significant (r = 0.86, p < 0.0001). Melanoma was bidirectionally associated with all 10 subtypes of NHL. The observed bidirectional associations between NHL and cancer suggest that therapy-related carcinogenic mechanisms cannot solely explain the findings. Considering that skin SCC and melanoma are usually treated by surgery and that these cancers and NHL are most responsive of any cancer to immune suppression, the consistent bidirectional results provide population-level evidence that immune suppressed state is a key underlying mechanism in the context of SPCs. Furthermore, the quantified risks for NHL subtypes have direct clinical application in the management of NHL patients.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
bi-directional risk, immune suppression, second cancers, therapeutic implication
in
International Journal of Cancer
volume
143
issue
10
pages
2449 - 2457
publisher
John Wiley & Sons
external identifiers
  • scopus:85053706664
ISSN
0020-7136
DOI
10.1002/ijc.31801
language
English
LU publication?
yes
id
d5e7f4a6-f2b5-4f5a-932b-0b9b0b215ee9
date added to LUP
2018-10-23 14:41:47
date last changed
2019-04-10 04:15:34
@article{d5e7f4a6-f2b5-4f5a-932b-0b9b0b215ee9,
  abstract     = {<p>Second primary cancers (SPCs) account for an increasing proportion of all cancer diagnoses. It is unlikely that prior therapy is solely responsible for SPC risk. To investigate risk of SPC after diagnosis of non-Hodgkin lymphoma (NHL) and 10 of its subtypes we conducted a novel bidirectional analysis, SPCs after NHL and NHL as SPC. Using the Swedish Family-Cancer Database, we identified 19,833 individuals with primary NHL diagnosed between 1993 and 2015. We calculated relative risks (RRs) of SPCs in NHL survivors and, for bi-directional analysis, risk of NHL as SPC. The overall RRs were significantly bidirectionally increased for NHL and 7 cancers. After diagnosis of NHL risks were increased for upper aerodigestive tract (RR = 1.96), colorectal (1.35), kidney (3.10), bladder (1.54) and squamous cell skin cancer (SCC) (4.12), melanoma (1.98) and Hodgkin lymphoma (9.38). The concordance between RRs for each bidirectional association between NHL and 31 different cancers was highly significant (r = 0.86, p &lt; 0.0001). Melanoma was bidirectionally associated with all 10 subtypes of NHL. The observed bidirectional associations between NHL and cancer suggest that therapy-related carcinogenic mechanisms cannot solely explain the findings. Considering that skin SCC and melanoma are usually treated by surgery and that these cancers and NHL are most responsive of any cancer to immune suppression, the consistent bidirectional results provide population-level evidence that immune suppressed state is a key underlying mechanism in the context of SPCs. Furthermore, the quantified risks for NHL subtypes have direct clinical application in the management of NHL patients.</p>},
  author       = {Chattopadhyay, Subhayan and Sud, Amit and Zheng, Guoqiao and Yu, Hongyao and Sundquist, Kristina and Sundquist, Jan and Försti, Asta and Houlston, Richard and Hemminki, Akseli and Hemminki, Kari},
  issn         = {0020-7136},
  keyword      = {bi-directional risk,immune suppression,second cancers,therapeutic implication},
  language     = {eng},
  month        = {09},
  number       = {10},
  pages        = {2449--2457},
  publisher    = {John Wiley & Sons},
  series       = {International Journal of Cancer},
  title        = {Second primary cancers in non-Hodgkin lymphoma : Bidirectional analyses suggesting role for immune dysfunction},
  url          = {http://dx.doi.org/10.1002/ijc.31801},
  volume       = {143},
  year         = {2018},
}