Influence of family history on risk of second primary cancers and survival in squamous cell skin cancer patients.

Chattopadhyay S1,2,3, Zheng G1,2,3, Hemminki A4,5, Försti A1,6,7,8, Sundquist K8,9,10, Sundquist J8,9,10, Hemminki K1,2,8,11.

Author information

1: Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, D-69120, Heidelberg, Germany.
2: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, D-69120, Heidelberg, Germany.
3: Faculty of Medicine, University of Heidelberg, Heidelberg, Germany.
4: Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland.
5: Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Finland.
6: Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.
7: Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany.
8: Center for Primary Health Care Research, Lund University, 205 02, Malmö, Sweden.
9: Department of Family Medicine and Community Health, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, USA.
10: Center for Community-based Healthcare Research and Education (CoHRE), Department of Functional Pathology, School of Medicine, Shimane University, Japan.
11: Faculty of Medicine and Biomedical Center in Pilsen, Charles University in Prague, 30605, Pilsen, Czech Republic.

Abstract

BACKGROUND:

Squamous cell skin cancer (SCC) patients have excellent prognosis but second primary cancers (SPCs) weaken survival prospects. Family history is a known risk factor for cancer but whether it is a risk factor for SPC in SCC patients is not known.

OBJECTIVE:

Quantify the risk of family history on SPCs in SCC patients and estimate survival probabilities of patients with SPCs depending on family history.

METHODS:

With 13,945 histologically verified SCCs, relative risks (RRs) were estimated for family history using a generalized regression model. For survival analysis, hazard ratios were assessed using a multivariable Cox-proportional hazard model.

RESULTS:

Family history of invasive SCC increased risk of second invasive SCC, RR = 42.92 (confidence intervals 33.69-50.32) compared to risk without family history RR 19.12 (17.88-21.08). Family history of any non-skin cancer in invasive SCC increased risk of the same cancers to be diagnosed as SPC; RRFH = 1.48 (1.35-1.61) vs. RRno FH = 1.40 (1.32-1.48); significant increases were observed for seven different non-skin cancers. Most results were replicated in in situ SCC. SPC was deleterious for survival irrespective of family history; hazard ratio for patients with SPC was 4.28 (3.83-4.72) compared to those without SPC (1.00).

CONCLUSION:

Family history of non-skin cancer was associated with approximately a doubling of risk for SPCs in SCC patients. SPC increases the death rate in SCC patients 3 to 4 times, irrespective of family history. Taking family history into account at SCC diagnosis may help prevention or early detection of SPCs.