We thank Dr. Lissing and colleagues for providing us with these helpful comments [1]. We are appreciative of your expertise and critical review of our work [2]. We have recognized that there were errors and will take the necessary steps to correct them.
After removing the overlapping articles, which in some cases were not very clear to us but following your assertions, we identified 13 articles, of which 3757 patients had porphyria (of any subtype) (Table 1). Overall, from this cohort, we identified 166 patients who developed cancer. We have also clearly laid out different types of porphyria and the number of cancer cases for each of those subtypes as per your recommendations; please see the table below.
Table 1.
Characteristics of patients with porphyria.
| Author/Year | Design | Location | Total Patients (n) | Total female n (%) | Age (Years), Mean ± SD | Age at Cancer Diagnosis (Years), Mean ± SD | α-Fetoprotein Levels | Porphyria Subtype with Cancer | Type of Cancer |
|---|---|---|---|---|---|---|---|---|---|
| Solis 1982 [3] | * Single-center | Spain | 138 PCT | 3 (2) | NR | 64 ± 7 | 780 ng/mL (1) 1320 ng/mL (1) 2150 ng/mL (1) Positive (5) ND (2) |
10 PCT | HCC (7) Unknown (3) |
| Salata 1985 [4] | Retrospective, single-center | Spain | 83 PCT | 6 (7.2) | 57 | 60 ± 5 | Elevated in 3 out of 9 HCC cases | 13 PCT | HCC (13) |
| Siersema 1992 [5] | Prospective, single-center | Netherlands | 38 PCT | 13 (34) | 48 ± 12 | 54 ± 4 | None were elevated | 5 PCT | HCC (5) |
| Kauppinen 1992 [6] | Retrospective, single-center | Finland | 206 (184 AIP, 61 VP) |
121 (58.7) | 49 (Range 21–96) | NR | NR | 6 AIP 1 VP |
HCC (7) |
| Andant 2000 [7] | Prospective, single-center | France | 650 (430 AIP, 136 VP, 84 HC) |
347 (53) | 41 ± 7 | 50 ± 10 | >200 IU/mL (7) | 5 AIP 1 VP 1 HC |
HCC (7) |
| Fracanzani 2001 [8] | Case–control, single-center | Italy | 53 PCT | 2 (3.8) | 56 ± 8 | NR | >400 UI/mL (1) | 18 PCT | HCC (18) |
| Gisbert 2004 [9] | Retrospective, Single-center | Spain | 39 PCT | 4 (10) | 55 ± 16 | 69 | Elevated (1) | 1 PCT | HCC (1) |
| Cassiman 2008 [10] | Retrospective, single-center | Belgium | 17 Sporadic PCT | 7 (41) | 43 ± 3 | NR | NR | 1 PCT | HCC (1) |
| Lang 2015 [11] | Questionnaire | Germany | 122 (97 AIP, 20 VP, 4 HC, 1 ADDP) |
NR | NR | NR | NR | 1 AIP | HCC (1) |
| Baravelli 2019 [12] | Retrospective, multicenter | Norway | 589 (243 sporadic PCT, 245 familial PCT, 101 unknown) |
319 (52) | 52 ± 13 | NR | NR | Did not classify | HCC (6) |
| Baravelli 2017 [13] | Retrospective, population registry | Norway | 251 (222 AIP, 21 VP, 8 HC) |
151 (60.2) |
Median (range) 53 (19–96) |
NR | NR | 8 AIP 1 VP |
HCC (9) |
| Saberi 2020 [14] | Retrospective, multicenter | USA | 327 (270 AIP, 19 HC, 38 VP) |
266 (81) | 32 ± 5 | 69 ± 5 | <10 ng/mL (4) | 4 AIP 1 VP |
HCC (5) |
| Lissing 2022 [15] | Retrospective, population registry | Sweden | 1244 (1063 AIP, 125 VP, 56 HC) |
654 (53) | Median (range) 36 (19–53) |
Median (range) 71 (53–89) |
NR | 81 AIP 1 VP 1 HCP |
HCC (67), CC (3), unspecified (13) |
* Study design (i.e., prospective, retrospective, etc.) unclear. AHP—Acute hepatic porphyrias, AIP—Acute intermittent porphyria, VP—Variegate porphyria, HC— Hereditary coproporphyria, PCT—Porphyria cutanea tarda, ADDP—δ-aminolaevulinic acid dehydratase-deficient porphyria, NR—Not reported, HCC—Hepatocellular carcinoma, and CC—Cholangiocarcinoma.
While disease severity would be interesting to assess, however, this is difficult to extract from these studies. However, we agree that a large cohort study with this information, including age, would be important for future research efforts.
Again, thank you for your comments.
Author Contributions
Conceptualization, D.R. and A.F.; methodology, D.R. and A.F.; validation, A.F.; data curation, D.R., S.S.D., S.C., J.L., J.S. (Jameel Singh), J.S. (Jayanta Samanta) and A.S.; writing—original draft preparation, D.R. and S.S.D.; writing—review and editing, D.R., S.d.N., M.G., F.P., F.C. and A.S.; supervision, D.R., A.F., R.S. and L.G. All authors have read and agreed to the published version of the manuscript.
Data Availability Statement
Not applicable.
Conflicts of Interest
The authors declare no conflict of interest.
Funding Statement
This research received no external funding.
Footnotes
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Data Availability Statement
Not applicable.