Second Primary Cancers in Patients with Invasive and In Situ Squamous Cell Skin Carcinoma, Kaposi Sarcoma, and Merkel Cell Carcinoma: Role for Immune Mechanisms?

Chattopadhyay, Subhayan; Hemminki, Akseli; Försti, Asta; Sundquist, Kristina; Sundquist, Jan; Hemminki, Kari

doi:10.1016/j.jid.2019.04.031

Cited by 9 publications

(13 citation statements)

References 39 publications

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“…14 Possible causes or contributing factors for SPCs are many, but probably the most important ones are intensive medical surveillance after the diagnosis of FPC, therapy for FPC, shared genetic or non-genetic risk factors between FPC and SPC and immune dysfunction elicited by FPC. 2,18,19 In the case of skin cancer therapy is not an issue, but medical surveillance probably is, because SPCs were diagnosed relatively shortly after skin cancers (2-3 years) which are generally diagnosed in elderly subjects (median diagnostic ages were 78-82 years in this study). 20 However, as practically all cancers reported to the Swedish Cancer Registry are histologically confirmed, the effect of medical surveillance would be antedating of diagnoses rather than introducing wrong diagnoses.…”

Section: Dovepressmentioning

confidence: 84%

<p>Incidence Differences Between First Primary Cancers and Second Primary Cancers Following Skin Squamous Cell Carcinoma as Etiological Clues</p>

Zheng¹,

Sundquist²,

Sundquist³

et al. 2020

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Background: Most literature on second primary cancers (SPCs) focuses on possible factors, which may increase the risk of these cancers, and little attention has been paid for the overall incidence differences between first primary cancers (FPCs) and same SPCs. We wanted to compare the incidence rates for all common cancers when these were diagnosed as FPCs and SPCs after invasive and in situ squamous cell carcinoma (SCC) of the skin, which are usually treated by surgery only. Methods: Cancers were identified from the Swedish Cancer Registry from the years 1990 through to 2015, and they included, in addition to skin cancers, 20 male cancers totaling 484,850 patients and 22 female cancers totaling 452,909 patients. Standardized incidence rates and relative risks (RRs) were calculated for sex-specific common cancers as FPC and as SPC after skin SCC. Spearman rank correlations were used in the analysis of incidence ranking of FPC and SPC. Results: Of total, 29,061 men and 23,533 women developed invasive SCC and 27,842 men and 36,383 women in situ SCC. The total number of 20 other male cancers was 484,850 and of 22 female cancers it was 452,909. Rank correlations ranged from 0.90 to 0.96 (P~5×10 −6), indicating that overall skin SCC did not interfere with SPC formation. The exceptions were increased SPC risks for melanoma, sharing risk factors with skin SCC, and non-Hodgkin and Hodgkin lymphoma, and cancers of the upper aerodigestive tract, connective tissue, and male and female genitals suggesting contribution by skin cancer initiated immune dysfunction. Conclusion: The incidence ranking of SPCs after skin cancers largely follows the incidence ranking of FPCs indicating that overall skin SCC does not greatly interfere with the intrinsic carcinogenic process. The main deviations in incidence between FPC and SPC appeared to be due to shared risk factors or immunological processes promoting immune responsive cancer types.

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Section: Dovepressmentioning

confidence: 84%

<p>Incidence Differences Between First Primary Cancers and Second Primary Cancers Following Skin Squamous Cell Carcinoma as Etiological Clues</p>

Zheng¹,

Sundquist²,

Sundquist³

et al. 2020

CLEP

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“… 29–31 An increased risk of GC as SPC has been found in studies analyzing SPCs after NHL and skin SCC. 32 , 33 It was also shown that family history of GC increased the likelihood of second GC in NHL patients. 34 We thus consider plausible that the increased risk for second GCs after skin SCC and NHL may have an immunological component.…”

Section: Discussionmentioning

confidence: 99%

Second Primary Cancers After Gastric Cancer, and Gastric Cancer as Second Primary Cancer

Zheng

Sundquist

Sundquist³

et al. 2021

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Background Second primary cancers (SPCs) are increasing, which may negatively influence patient survival. Gastric cancer (GC) has poor survival and when it is diagnosed as SPC it is often the cause of death. We wanted to analyze the risk of SPCs after GC and the risk of GC as SPC after any cancer. Such bidirectional analysis is important in relation to fatal cancers because SPCs may be under-reported in the short-term survival period. Methods Cancers were obtained from the Swedish Cancer Registry from years 1990 through 2015. Standardized incidence ratios (SIRs) were used to estimate bidirectional relative. Results We identified 23,137 GC patients who developed 1042 SPCs (4.5%); 2158 patients had GC as SPC. While the risk for three SPCs was increased after GC, seven first primary cancers were followed by an increased risk of GC as SPC, including esophageal, colorectal, bladder, squamous cell skin and breast cancers and non-Hodgkin lymphoma. Breast cancer, which was followed by a diagnosis of second GC, showed an excess of lobular histology. Conclusion Multiple primary cancers in the same individuals may signal genetic predisposition. Accordingly, the association of GC with breast cancer may be related to mutations in the CDH1 gene, and clustering of colorectal, small intestinal and bladder cancers could be related to Lynch syndrome. The third line of findings supports a contribution of immune dysfunction on the increased risk of GC as SPC after skin cancer and non-Hodgkin lymphoma. Early detection of GC in the risk groups could save lives.

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“…Plausible etiologies for SPCs are many, but probably the most important ones are intensive medical surveillance (surveillance bias) after the diagnosis of the first primary cancer (FPC), therapy for FPC, shared genetic or nongenetic risk factors between FPC and SPC, and immune dysfunction elicited by FPC, or interactions between these [10] , [11] , [12] . As data on the possible risk factors for SPCs are usually limited, we have devised a bidirectional analysis as a tool to help interpret the findings [11] , [13] , [14] .…”

Section: Introductionmentioning

confidence: 99%

Second Primary Cancers After Kidney Cancers, and Kidney Cancers as Second Primary Cancers

Zheng

Sundquist

et al. 2021

European Urology Open Science

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Background Second primary cancers (SPCs) are increasing due to improving survival in first primary cancers. Previous studies on SPCs in renal cell carcinoma (RCC) have focused on treatment and other risk factors, but data of RCC as an SPC are scarce. Objective In this study, we want to elucidate the risk for any SPC after RCC, and in reverse order, for RCC as an SPC after any cancer. We additionally consider how family histories influence the risks. Design, setting, and participants Patient data were obtained from the Swedish Cancer Registry from years 1990 through 2015, and family data were obtained from the Multigeneration Register. Outcome measurements and statistical analysis We employed standardized incidence ratios to estimate bidirectional relative risks of subsequent cancer associated with RCC. Results and limitations We identified 17 587 RCCs (60% in male patients). The highest increases for SPCs were observed for nervous system hemangioblastoma (HB; 26.8), adrenal (12.09) tumors, and renal pelvic cancer (6.32). In the reverse order, RCC as an SPC, nervous system HB (17.01), and adrenal tumors (15.34) were associated with the highest risks. Risks for many other sites (12 sites and subsites) were increased bidirectionally. For women, a total of seven sites and subsites were increased bidirectionally, and many were shared with men. The only significant sex difference in SPCs was the higher lung cancer risk in women (2.41) than in men (1.28). Patients with a family history of HBs or of prostate, colorectal and lung cancers showed high risks of these cancers as SPCs after RCC. Family history accounted for 30% of prostate cancers after RCC. Conclusions The bidirectional study design was able to suggest risk factors for SPCs and offered a clinical take-home message urging to consider strategies for early detection and prevention of SPCs. Readily available information on lifestyle (eg, smoking) and family history (eg, prostate cancer) may reveal targets for risk reduction with prognostic benefits. Patient summary Close to 10% of kidney cancer patients develop another cancer. The cause for these other cancers may not depend on kidney cancer.

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Second Primary Cancers in Patients with Invasive and In Situ Squamous Cell Skin Carcinoma, Kaposi Sarcoma, and Merkel Cell Carcinoma: Role for Immune Mechanisms?

Cited by 9 publications

References 39 publications

<p>Incidence Differences Between First Primary Cancers and Second Primary Cancers Following Skin Squamous Cell Carcinoma as Etiological Clues</p>

<p>Incidence Differences Between First Primary Cancers and Second Primary Cancers Following Skin Squamous Cell Carcinoma as Etiological Clues</p>

Second Primary Cancers After Gastric Cancer, and Gastric Cancer as Second Primary Cancer

Second Primary Cancers After Kidney Cancers, and Kidney Cancers as Second Primary Cancers

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