Risk of Second Primary Cancer in People with Non-melanoma Skin Cancer: A Nationwide Cohort Study

Shu-Hui Wang; Ching-Chi Chi; Zi-Hao Zhao; Tao-Hsin Tung

doi:10.4143/crt.2017.110

Articles

Page Path: HOME > Cancer Res Treat > Volume 50(2); 2018 > Article

Original Article Risk of Second Primary Cancer in People with Non-melanoma Skin Cancer: A Nationwide Cohort Study: Shu-Hui Wang, MD, MS^1,2, Ching-Chi Chi, MD, MMS, DPhil^3,4,, Zi-Hao Zhao, MPH¹, Tao-Hsin Tung, PhD^5,6,; Cancer Research and Treatment : Official Journal of Korean Cancer Association 2018;50(2):428-435.
DOI: https://doi.org/10.4143/crt.2017.110
Published online: May 10, 2017

¹Department of Dermatology, Far Eastern Memorial Hospital, New Taipei, Taiwan

²Graduate Institute of Applied Science and Engineering, College of Science and Engineering, Fu Jen Catholic University, New Taipei, Taiwan

³Department of Dermatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan

⁴College of Medicine, Chang Gung University, Taoyuan, Taiwan

⁵Department of Medical Research and Education, Cheng Hsin General Hospital, Taipei, Taiwan

⁶Department of Public Health, Fu Jen Catholic University, New Taipei, Taiwan

Correspondence: Ching-Chi Chi, MD, MMS, DPhil Department of Dermatology, Chang Gung Memorial Hospital, Linkou, 5, Fuxing St, Guishan Dist, Taoyuan 33305, Taiwan
Tel: 886-3-328-1200 Fax: 886-3-328-1300 E-mail: chingchi@cgmh.org.tw

Co-correspondence: Tao-Hsin Tung, PhD Department of Medical Research and Education, Cheng Hsin General Hospital, 45, Cheng Hsin St, Pai-Tou, Taipei 11220, Taiwan
Tel: 886-2-2826-4400 Fax: 886-2-2826-4550 E-mail: ch2876@chgh.org.tw

• Received: March 3, 2017 • Accepted: May 6, 2017

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

10,527 Views
170 Download
2 Web of Science
2 Crossref
2 Scopus

prev next

Full Article

Download PDF

Abstract

Purpose
Previous western studies have found Caucasians with skin cancer, either melanoma or nonmelanoma skin cancer (NMSC), have an elevated risk of second primary cancer. Our objective was to assess the risk of second primary cancer in Taiwanese with NMSC.
Materials and Methods
By using data from Taiwan’s National Health Insurance Research Database, we conducted a population-based cohort study to assess the risk of incident second primary cancer in Taiwanese affected by NMSC.
Results
We identified 505 subjects with NMSC and 2,020 matched controls. After adjustment for potential confounders including age, sex, urbanization, and Charlson Comorbidity Index, people who had NMSC had a 1.43-fold (95% confidence interval [CI], 1.05 to 1.96) risk for the development of second primary cancer as comparedwith control group. Menwith NMSC had a 2.99-fold (95% CI, 1.00 to 9.10) risk for second primary cancer involving the lip, oral cavity, and pharynx and a 3.51-fold (95% CI, 1.21 to 10.17) risk for second primary cancer involving the genitourinary organs when compared to the control group. By contrast, women with NMSC did not have an increased risk of second primary cancer.
Conclusion
This study revealed Asians with NMSC have an increased risk of second primary cancer. Our findings can be a useful reference for health care for people diagnosed with NMSC.
Key words: Charlson comorbidity index, Non-melanoma skin cancer, Population-based study, Second primary neoplasms

Introduction

The formation of cancer may be related to environmental carcinogens, genes and immunity of the subject. The formation of skin cancer is also related to these factors. A person with a cancer might represent that there are abnormalities in environment and genes of this subject; therefore, the subject has an increased opportunity of having a second primary cancer involving other organs. Such an increased risk of second primary cancer has been observed in people affected by gastrointestinal cancer and head and neck cancer [1,2]. Also, previous western studies have found Caucasians with skin cancer, either melanoma or non-melanoma skin cancer (NMSC), have an elevated risk of second primary cancer [3,4]. On the other hand, ultraviolet radiation, the main environmental cause of skin cancer, is known to promote the synthesis of vitamin D which in turn has been associated with a decrease in the risk of prostate, breast, and colorectal cancer [5]. A Dutch study identified a lowered risk of colorectal cancer in people with skin cancer [6], but a Swiss study found the risk of prostate, breast and colorectal cancer all increased in those with skin cancer [5].

Previous western studies identified men and women differed in the risk for various subsequent cancers. A U.S. study found men with NMSC had an increased risk of subsequent melanoma, while women with NMSC had an increased risk of subsequent breast and lung cancer as well as melanoma [4]. A Norwegian study showed men with melanoma were prone to have subsequent prostate and thyroid cancers, whereas women with melanoma were more likely to have subsequent cancers involving the breast and central nervous system [3].

A study found an elevated risk of second primary cancer in Asians with melanoma [7]. However, to date there have been no similar studies examining whether Asians with NMSC have an increased risk of second primary cancer involving other organs.

The objective of this retrospective cohort study was to assess whether people diagnosed with a NMSC would have an increased risk of second primary cancer involving other organs in a Taiwanese setting. It is expected that the results of this study will be a useful reference for health education and preventive medicine interventions for people diagnosed with NMSC.

Materials and Methods

1. Data source

In Taiwan, over 99% of the population is covered by a compulsory single-payer healthcare system, the National Health Insurance program. The National Health Insurance Research Database (NHIRD) provides anonymized linked data for epidemiologic research, including the characteristics and registration data of beneficiaries, claim data from general practices and hospitals, and dispensing claims from general practices, hospitals, and community pharmacies. The International Classification of Diseases ninth revision Clinical Modification (ICD-9-CM) was used to record diagnoses in the NHIRD. The wholeness and accuracy of the NHIRD linked data such as clinical diagnoses have been validated [8,9]. The NHIRD has been widely used in thousands of epidemiological studies [10].

The data source of this study was the Longitudinal Health Insurance Database 2000 of NHIRD, which is the anonymized linked longitudinal data of 1,000,000 beneficiaries (about 4.5% of the Taiwanese population) randomly selected from the 2000 Registry for Beneficiaries. The National Health Insurance (NHI) issues a catastrophic illness record to patients with cancer which exempts them from paying a co-payment. Eligible patients need to provide a copy of histopathologic report confirming the diagnosis of cancer when applying for a catastrophic illness record [11].

2. Study subjects

The selection of study subjects is shown in Fig. 1. The exposed group (NMSC group) was composed of people with NMSC diagnosed by dermatologists and who had been issued a corresponding catastrophic illness card from 2000 onwards. People who had a diagnosis of NMSC but lacked a corresponding catastrophic illness record were excluded. We also excluded subjects aged under 20 years and those who had another cancer occurred before the diagnosis of NMSC. We used ICD-9-CM codes (173.xx) to identify subjects diagnosed with NMSC and had catastrophic illness record. The non-skin cancer control group was composed of those who had not ever been diagnosed as having skin cancer, either NMSC or melanoma. To adjust for differences in subject profiles which may confound the study findings, we selected four controls for each NMSC case by using propensity score matching for patient’s demographic characteristics including age, sex, and urbanization. The propensity score matching analysis was used to conduct probability by logistic regression model [12]. The date of first diagnosis of NMSC was the index date for a NMSC patient and its four corresponding controls.

3. Outcomes and potential confounders

The outcome of our interest was second primary cancer, identified by having a diagnosis of cancer (ICD-9-CM codes from 140.xx to 209.xx) and a corresponding catastrophic illness record following the index date [4,7,13]. The date of first diagnosis of NMSC in either outpatient or inpatient records was the index date in a NMSC case and its four corresponding controls. We also examined which organ the second primary cancer involved. The ICD-9-CM codes used for identification of the organ involved included lip, oral cavity, and pharynx (140.xx-149.xx), digestive organs and peritoneum (150.xx-159.xx), respiratory and intrathoracic organs (160.xx-165.xx), bone, connective tissue (170.xx-171.xx), melanoma (172.xx), female breast (174.xx), male breast (175.xx), female genital (179.xx-184.xx), male genital (185.xx-187.xx), urinary (188.xx-189.xx), eyes (190.xx), brain and nervous system (191.xx-192.xx), and thyroid gland and endocrine (193.xx-194.xx). NMSC (173.xx), other and illdefined sites (195.xx and 199.xx), and secondary malignant neoplasm (196.xx-198.xx) that did not indicate the involved organ were excluded. The follow-up duration for subjects who ended up with a second primary cancer was the period from the index date to the date of first diagnosis in either inpatient or outpatient records, and for the censored time of subjects without second primary cancer or death were from the index date to either the end of 2012 or the date of withdrawal from the NHI program.

To mitigate potential sources of bias, we considered and adjusted potential confounders including the age, urbanization, and the Charlson Comorbidity Index (CCI). The CCI is a prognostic index used as a means for quantifying the prognosis of patients [14]. A weighted score was assigned to each of 17 comorbidities and the Charlson index was then created as an indicator of disease burden for risk adjustment [15]. Therefore, the confounding of comorbidities on the risk of developing second primary cancer was considered and adjusted in the statistical analysis.

4. Statistical analysis

The Student’s t test and chi-square test were used to compare continuous and categorical data. The Kaplan-Meier method was used for survival analysis with the log-rank test for comparisons between the NMSC and control groups. The cumulative incidence of developing second primary cancer was one minus the cancer-free survival probability [16]. The Cox proportional hazard regression model was proceeded to obtain the hazard ratio (HR) for development of incident second primary cancer among patients with NMSC. To examine the involved organ of the second primary cancer (listed as above), we used the Cox regression analysis to calculate the respective HR of second primary cancer of each organ, stratified by sex and adjusted for potential confounders including age, urbanization, and CCI. We considered a two-sided p-value of < 0.05 significant. All statistical analyses were conducted by using the SAS software ver. 9.3 (SAS Institute Inc., Cary, NC).

5. Ethics approval

This study has been approved by the Institutional Review Board of the Chen Hsin General Hospital, Taiwan ((504)104-40).

Results

The characteristics and potential confounders of the study subjects are listed in Table 1. We identified 505 people with NMSC and 2,020 matched controls without NMSC. No significant differences in the age and gender distribution, urbanization as well as the length of follow up were found between the NMSC and control groups. A higher score of CCI was found with NMSC patient compared to people without NMSC, being 4.7±3.2 and 3.3±2.7, respectively.

As show in Table 2, the NMSC group had a twice higher incidence of second primary cancer than the control group. The Kaplan-Meier curves of cumulative incidence for second primary cancer are shown in Fig. 2. The NMSC group had a significant higher probability of developing second primary cancer than controls (p=0.024) (Fig. 2A). When compared to the control group, the NMSC group had an increased risk of second primary cancer (crude, 1.87; 95% confidence interval [CI], 1.37 to 2.55). After controlling for potential confounders including age, sex, urbanization, and CCI, the adjusted HR was 1.43 (95% CI, 1.05 to 1.96).

When stratified by sex, both men and women with NMSC had a nearly twice higher incidence of second primary cancer than their respective controls. As shown in Fig. 2B and C, men with NMSC had a higher probability of second primary cancer than controls (p=0.043), but women did not (p=0.235). After adjusted for potential confounders, men with NMSC had a significantly higher risk of second primary cancer than controls (adjusted HR, 1.51; 95% CI, 1.01 to 2.25) but women with NMSC did not (adjusted HR, 1.35; 95% CI, 0.82 to 2.24).

In the analysis according to involved organ of second primary cancer, men with NMSC had a significant higher risk of second primary cancer involving the lip, oral cavity, pharynx (adjusted HR, 2.99; 95% CI, 1.00 to 9.10) and the genitourinary organs (adjusted HR, 3.51; 95% CI, 1.21 to 10.17) (Table 3). The Kaplan-Meier curves of cumulative incidence for second primary cancer involving the lip, oral cavity, pharynx and the genitourinary organs in men are shown in Fig. 3A and B. Compared to the control group, men with NMSC had a significantly higher probability of second primary cancer affecting the lip, oral cavity, pharynx (p=0.050), and the genitourinary organs (p=0.021).

Discussion

To the best of our knowledge, this study was the first to examine the relation between NMSC and subsequent malignancy in Asians. This study found only men with NMSC had a two-fold risk of second primary cancer compared to controls, while women with NMSC did not. When further analyzed according to the involved sites, the increased risk of second primary cancer in men with NMSC was attributable to those involving the lip, oral cavity, and pharynx as well as the genitourinary organs.

Overall our study found NMSC was associated with an increased risk of only few second primary cancers, while other studies in the Western countries reported associations of NMSC with a larger number of second primary cancers. Our findings are in congruent with a Norwegian study which found men with squamous cell carcinoma had an increased risk of second primary cancer involving the mouth, pharynx, salivary glands, and prostate [3]. However, the Norwegian study also found an additional increased risk of melanoma, hematological malignancies, and other second primary cancers involving the lung and pancreas [3]. Similar to our findings, a Canadian study also found men with NMSC had an increased risk of second primary cancer involving the lip, oral cavity, and pharynx as well as the kidney [13]. Nevertheless, the Canadian study did not an increase in the risk of genital organs in men with NMSC. The Canadian study also found an increased risk of second primary cancer involving more than 20 other organs [13].

In contrast to our findings, an U.S. study found no increased risk of second primary cancer involving the lip, oral cavity, pharynx, and genitourinary organs in men with NMSC [4]. The U.S. study identified an increased risk of melanoma in people with NMSC and an increased risk of breast cancer and lung cancer in women with NMSC [4].

People with skin cancer have been assumed to have a higher exposure to ultraviolet radiation that promotes the synthesis of vitamin D which reduces the risk of prostate, breast, and colorectal cancer [5]. However, our study found no significant differences in the risk of prostate, breast, and colorectal cancer between people with and without NMSC, which was similar to the findings of a U.S. study [17]. By contrast, a Dutch study illustrated a decreased risk of developing colorectal cancer in people with skin cancer [6], and an U.K. study reported a lower risk of breast, and prostate cancers in those with basal cell carcinoma [18]. Meanwhile a Swiss study found the risk of prostate, breast, and colorectal cancer was escalated in people with skin cancer [5], and a U.S. study revealed an increased risk of breast and colorectal cancer in those with skin cancer [19]. The contradictory findings from various studies indicate the pathogenesis of prostate, breast, and colorectal cancer is complicated and cannot be explained by vitamin D alone.

In this study only men with NMSC had an increased risk of second primary cancers while women did not. To the best of our knowledge, all previous studies reported an increased risk of subsequent primary cancers in both genders. The cause for the male sex being an effect modifier in this study was unclear. Men are known to be more likely than women to own unhealthy lifestyles of smoking and alcohol drinking in Taiwan [20], and may thus have a higher risk of having certain cancers for example cancer of the urinary tract [21]. However, we could not adjust these lifestyle confounders in our analysis due to the lack of relevant data in the NHIRD.

The cause for various presentations of second primary cancer in people with NMSC across the world is unclear, which may be attributed to different genetic and environmental factors across various ethnic groups. For example, the incidence of prostate, breast, and colorectal cancer in Asians is much lower than that in the Western countries [22]. The lower background incidence of these cancers might have led to the lack of significant differences in the corresponding risk between people with and without NMSC in this study.

All the three Western studies used analysis involving standardization of incidence and could not adequately adjust for potential confounders [3,4,13]. Our study adjusted a range of potential confounders including the age, urbanization and CCI, and thus obtained less biased risk estimates than previous studies. Another strength of our study was the lengthy study period of up to 12 years, which allowed us to examine the long-term impact of NMSC on the risk of second primary cancers.

This study has several few limitations. Firstly, the sample size of this study was limited and some finding might be the result of random chance. Further studies are warranted to confirm our findings. Secondly, misclassification bias might exist as a few subjects with NMSC might not apply for catastrophic illness record. Also, those with second primary cancer might have not applied for catastrophic illness record as well. However, such misclassification only led to an underestimation of the observed increased risk of second primary cancer in those with NMSC. Thirdly, there were a few factors that might have affected the development of second primary cancer but we were unable to control due to lack of relevant data, for example, family history of cancer, exposure of carcinogens, co-existence of inflammatory disease (such as Crohn disease and psoriasis), metabolic syndrome, and use of immunosuppressants. However, we have mitigated the selection bias by use of propensity score matching by age, sex, and urbanization in selecting controls, use of the same index date for NMSC cases and controls, and adjustment of potential confounders including CCI in the analysis.

In conclusion, people with NMSC have an increased risk of second primary cancer. We found Asian men with NMSC had an increased risk of second primary cancer involving the lip, oral cavity, and pharynx as well as the genitourinary organs. The results of this study can be a useful reference for health education and preventive medicine interventions for people diagnosed with NMSC. A specific checkup program for people with NMSC that includes not only skin examination but also examination of other organ systems, especially the lip, oral cavity, pharynx, and the genitourinary organs, is warranted.

NOTES

Conflict of interest relevant to this article was not reported.

Acknowledgements

Far Eastern Memorial Hospital, New Taipei, Taiwan (FEMH-2016-C-038).

Fig. 1.

Flow chart of selection of the study population. NMSC, non-melanoma skin cancer.

Fig. 2.

Cumulative incidence curves of second primary cancer in people with non-melanoma skin cancer (NMSC). (A) All subjects. (B) Men. (C) Women.

Fig. 3.

Cumulative incidence curves of second primary cancer involving the lip, oral cavity, pharynx (A), and the genitourinary organs (B) in men. NMSC, non-melanoma skin cancer.

Table 1.

Characteristics and potential confounders of the study subjects

	Control (n=2,020)	Non-melanoma skin cancer group (n=505)	p-value
Sex
Women	1,024 (80.0)	256 (20.0)	1.000
Men	996 (80.0)	249 (20.0)
Age (yr)	67.2±15.2	67.2±15.4	0.96
Urbanization
City	893 (44.2)	223 (44.2)	1.000
Suburbs	747 (37.0)	187 (37.0)
Village	380 (18.8)	95 (18.8)
Charlson Comorbidity Index	3.3±2.7	4.7±3.2	< 0.001
Length of follow-up (yr)	6.0±3.0	5.7±3.1	0.05

Values are presented as number (%) or mean±standard deviation.

Table 2.

Risk of second primary cancer in people with non-melanoma skin cancer

	No.	No. of incident second primary cancer	No. of person-years	Incidence (per 10² person-year)	Adjusted HR (95% CI)^a)
Total	2,525	188	14,931.71	1.26 (1.09-1.45)	-
Control	2,020	130	12,068.08	1.08 (0.90-1.27)	1.00 (reference)
NMSC	505	58	2,863.63	2.03 (1.55-2.59)	1.43 (1.05-1.96)
All men	1,245	116	7,345.79	1.58 (1.31-1.88)	-
Control	1,129	80	5,972.34	1.34 (1.07-1.65)	1.00 (reference)
NMSC	116	36	1,373.45	2.62 (1.86-3.57)	1.51 (1.01-2.25)
All women	1,280	72	7,585.93	0.95 (0.75-1.19)	-
Control	1,208	50	6,095.75	0.82 (0.61-1.07)	1.00 (reference)
NMSC	72	22	1,490.18	1.48 (0.94-2.18)	1.35 (0.82-2.24)

HR, hazard ratio; CI, confidence interval; NMSC, non-melanoma skin cancer.

^a) Adjusted for age, sex, urbanization, and Charlson Comorbidity Index.

Table 3.

Stratified analysis based on sex

Second primary cancer	Men (n=1,245)			Women (n=1,280)
	No. (%)		Adjusted HR (95% CI)^a)	No. (%)		Adjusted HR (95% CI)^a)
	Control (n=996)	NMSC (n=249)	Adjusted HR (95% CI)^a)	Control (n=1,024)	NMSC (n=256)	Adjusted HR (95% CI)^a)
Lip, oral cavity, and pharynx	7 (0.7)	6 (2.4)	2.99 (1.00-9.10)	1 (0.1)	0	-
Digestive organs and peritoneum	33 (3.3)	9 (3.6)	0.88 (0.98-1.03)	24 (2.3)	3 (1.2)	0.38 (0.11-1.26)
Colorectal	14 (1.4)	4 (1.6)	0.93 (0.30-2.87)	12 (1.2)	1 (0.4)	0.25 (0.03-1.96)
Respiratory and intrathoracic organs	14 (1.4)	3 (1.2)	0.73 (0.21-2.57)	4 (0.4)	2 (0.8)	1.46 (0.27-8.03)
Bone, articular cartilage, connective, and other soft tissue	0	3 (1.2)	-	2 (0.2)	2 (0.8)	2.85 (0.40-20.24)
Melanoma	0	1 (0.4)	-	0	3 (1.2)	-
Breast	0	0	-	6 (0.6)	5 (2.0)	2.58 (0.79-8.50)
Genital	10 (1.0)	2 (0.8)	0.76 (0.16-3.53)	6 (0.6)	1 (0.4)	0.54 (0.06-4.49)
Genitourinary organs	7 (0.7)	7 (2.8)	3.51 (1.21-10.17)	2 (0.2)	2 (0.8)	3.21 (0.45-22.98)
Prostate	9 (0.9)	2 (0.8)	0.86 (0.18-4.06)	-	-	-
Eyes	0	1 (0.4)	-	0	1 (0.4)	-
Brain and nervous system	0	0	-	1 (0.1)	0	-
Thyroid gland and endocrine glands	2 (0.2)	0	-	1 (0.1)	0	-
Lymphatic and hematopoietic tissue	5 (0.5)	1 (0.4)	0.7 (0.08-6.12)	2 (0.2)	0	-

NMSC, non-melanoma skin cancer; HR, hazard ratio; CI, confidence interval.

^a) Adjusted for age, sex, urbanization, and Charlson Comorbidity Index.

REFERENCES

1. Chuang SC, Hashibe M, Scelo G, Brewster DH, Pukkala E, Friis S, et al. Risk of second primary cancer among esophageal cancer patients: a pooled analysis of 13 cancer registries. Cancer Epidemiol Biomarkers Prev. 2008;17:1543–9. Article PubMed
2. Chuang SC, Scelo G, Tonita JM, Tamaro S, Jonasson JG, Kliewer EV, et al. Risk of second primary cancer among patients with head and neck cancers: a pooled analysis of 13 cancer registries. Int J Cancer. 2008;123:2390–6. Article PubMed
3. Robsahm TE, Karagas MR, Rees JR, Syse A. New malignancies after squamous cell carcinoma and melanomas: a populationbased study from Norway. BMC Cancer. 2014;14:210.Article PubMed PMC PDF
4. Song F, Qureshi AA, Giovannucci EL, Fuchs CS, Chen WY, Stampfer MJ, et al. Risk of a second primary cancer after nonmelanoma skin cancer in white men and women: a prospective cohort study. PLoS Med. 2013;10:e1001433Article PubMed PMC
5. Levi F, Randimbison L, Te VC, Conconi MM, La Vecchia C. Risk of prostate, breast and colorectal cancer after skin cancer diagnosis. Int J Cancer. 2008;123:2899–901. Article PubMed
6. Soerjomataram I, Louwman WJ, Lemmens VE, Coebergh JW, de Vries E. Are patients with skin cancer at lower risk of developing colorectal or breast cancer? Am J Epidemiol. 2008;167:1421–9. Article PubMed PDF
7. Hwang CY, Chen YJ, Lin MW, Chen TJ, Chu SY, Chen CC, et al. Elevated risk of second primary cancer in patients with cutaneous malignant melanoma: a nationwide cohort study in Taiwan. J Dermatol Sci. 2010;60:167–72. Article PubMed
8. Cheng CL, Kao YH, Lin SJ, Lee CH, Lai ML. Validation of the National Health Insurance Research Database with ischemic stroke cases in Taiwan. Pharmacoepidemiol Drug Saf. 2011;20:236–42. Article PubMed
9. Wu CS, Lai MS, Gau SS, Wang SC, Tsai HJ. Concordance between patient self-reports and claims data on clinical diagnoses, medication use, and health system utilization in Taiwan. PLoS One. 2014;9:e112257Article PubMed PMC
10. Hsing AW, Ioannidis JP. Nationwide population science: lessons from the Taiwan National Health Insurance Research Database. JAMA Intern Med. 2015;175:1527–9. Article PubMed
11. National Health Insurance Administration. Patients with catastrophic illnesses or rare diseases [Internet]. Taipei: National Health Insurance Administration; c2017. [cited 2017 Apr 18]. Available from: http://www.nhi.gov.tw/English/webdata/webdata.aspx?menu=11&menu_id=596&webdata_id=3180&WD_ID=596
12. D'Agostino RB Jr. Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group. Stat Med. 1998;17:2265–81. Article PubMed
13. Jung GW, Dover DC, Salopek TG. Risk of second primary malignancies following a diagnosis of cutaneous malignant melanoma or nonmelanoma skin cancer in Alberta, Canada from 1979 to 2009. Br J Dermatol. 2014;170:136–43. Article PubMed
14. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40:373–83. Article PubMed
15. Li B, Evans D, Faris P, Dean S, Quan H. Risk adjustment performance of Charlson and Elixhauser comorbidities in ICD-9 and ICD-10 administrative databases. BMC Health Serv Res. 2008;8:12.Article PubMed PMC PDF
16. Satagopan JM, Ben-Porat L, Berwick M, Robson M, Kutler D, Auerbach AD. A note on competing risks in survival data analysis. Br J Cancer. 2004;91:1229–35. Article PubMed PMC PDF
17. Efird JT, Friedman GD, Habel L, Tekawa IS, Nelson LM. Risk of subsequent cancer following invasive or in situ squamous cell skin cancer. Ann Epidemiol. 2002;12:469–75. Article PubMed
18. Bower CP, Lear JT, Bygrave S, Etherington D, Harvey I, Archer CB. Basal cell carcinoma and risk of subsequent malignancies: a cancer registry-based study in southwest England. J Am Acad Dermatol. 2000;42:988–91. Article PubMed
19. Rosenberg CA, Greenland P, Khandekar J, Loar A, Ascensao J, Lopez AM. Association of nonmelanoma skin cancer with second malignancy. Cancer. 2004;100:130–8. Article PubMed
20. Chuang YC, Chuang KY. Gender differences in relationships between social capital and individual smoking and drinking behavior in Taiwan. Soc Sci Med. 2008;67:1321–30. Article PubMed
21. Zeegers MP, Tan FE, Verhagen AP, Weijenberg MP, van den Brandt PA. Elevated risk of cancer of the urinary tract for alcohol drinkers: a meta-analysis. Cancer Causes Control. 1999;10:445–51. Article PubMed
22. Jemal A, Center MM, DeSantis C, Ward EM. Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol Biomarkers Prev. 2010;19:1893–907. Article PubMed

Figure & Data

REFERENCES

Citations

Citations to this article as recorded by

Epidemiological and genetic insights into the co-occurrence of cutaneous melanoma and hematologic malignancies: A meta-analytic review
Ashmitha Kumar, Arunan Jeyakumar, Alfred K. Lam, Vinod Gopalan
Leukemia Research.2024; 147: 107610. CrossRef
Non‐melanoma skin cancer as a clinical marker for internal malignancies: a nationwide population‐based cohort study
S.J. Yun, J.M. Bae, H. Kim, B.C. Park, J.S. Kim, S.H. Seo, H.H. Ahn, D.Y. Lee, Y.C. Kim, H.J. Park, K.Y. Chung
Journal of the European Academy of Dermatology and Venereology.2020; 34(4): 746. CrossRef

PubReader
ePub Link

Cite

CITE: export Copy Download Format; Close

Download Citation

Download a citation file in RIS format that can be imported by all major citation management software, including EndNote, ProCite, RefWorks, and Reference Manager.

Format:

RIS — For EndNote, ProCite, RefWorks, and most other reference management software
BibTeX — For JabRef, BibDesk, and other BibTeX-specific software

Include:

Citation for the content below
Citation and abstract for the content below

Risk of Second Primary Cancer in People with Non-melanoma Skin Cancer: A Nationwide Cohort Study

Cancer Res Treat. 2018;50(2):428-435. Published online May 10, 2017

DOI: https://doi.org/10.4143/crt.2017.110

XML Download

Abstract
Introduction
Materials and Methods
Results
Discussion
NOTES
REFERENCES

Risk of Second Primary Cancer in People with Non-melanoma Skin Cancer: A Nationwide Cohort Study

Fig. 1. Flow chart of selection of the study population. NMSC, non-melanoma skin cancer.

Fig. 2. Cumulative incidence curves of second primary cancer in people with non-melanoma skin cancer (NMSC). (A) All subjects. (B) Men. (C) Women.

Fig. 3. Cumulative incidence curves of second primary cancer involving the lip, oral cavity, pharynx (A), and the genitourinary organs (B) in men. NMSC, non-melanoma skin cancer.

Fig. 1.

Fig. 2.

Fig. 3.

Risk of Second Primary Cancer in People with Non-melanoma Skin Cancer: A Nationwide Cohort Study

	Control (n=2,020)	Non-melanoma skin cancer group (n=505)	p-value
Sex
Women	1,024 (80.0)	256 (20.0)	1.000
Men	996 (80.0)	249 (20.0)
Age (yr)	67.2±15.2	67.2±15.4	0.96
Urbanization
City	893 (44.2)	223 (44.2)	1.000
Suburbs	747 (37.0)	187 (37.0)
Village	380 (18.8)	95 (18.8)
Charlson Comorbidity Index	3.3±2.7	4.7±3.2	< 0.001
Length of follow-up (yr)	6.0±3.0	5.7±3.1	0.05

	No.	No. of incident second primary cancer	No. of person-years	Incidence (per 10² person-year)	Adjusted HR (95% CI)^a)
Total	2,525	188	14,931.71	1.26 (1.09-1.45)	-
Control	2,020	130	12,068.08	1.08 (0.90-1.27)	1.00 (reference)
NMSC	505	58	2,863.63	2.03 (1.55-2.59)	1.43 (1.05-1.96)
All men	1,245	116	7,345.79	1.58 (1.31-1.88)	-
Control	1,129	80	5,972.34	1.34 (1.07-1.65)	1.00 (reference)
NMSC	116	36	1,373.45	2.62 (1.86-3.57)	1.51 (1.01-2.25)
All women	1,280	72	7,585.93	0.95 (0.75-1.19)	-
Control	1,208	50	6,095.75	0.82 (0.61-1.07)	1.00 (reference)
NMSC	72	22	1,490.18	1.48 (0.94-2.18)	1.35 (0.82-2.24)

Second primary cancer	Men (n=1,245)			Women (n=1,280)
	No. (%)		Adjusted HR (95% CI)^a)	No. (%)		Adjusted HR (95% CI)^a)
	Control (n=996)	NMSC (n=249)	Adjusted HR (95% CI)^a)	Control (n=1,024)	NMSC (n=256)	Adjusted HR (95% CI)^a)
Lip, oral cavity, and pharynx	7 (0.7)	6 (2.4)	2.99 (1.00-9.10)	1 (0.1)	0	-
Digestive organs and peritoneum	33 (3.3)	9 (3.6)	0.88 (0.98-1.03)	24 (2.3)	3 (1.2)	0.38 (0.11-1.26)
Colorectal	14 (1.4)	4 (1.6)	0.93 (0.30-2.87)	12 (1.2)	1 (0.4)	0.25 (0.03-1.96)
Respiratory and intrathoracic organs	14 (1.4)	3 (1.2)	0.73 (0.21-2.57)	4 (0.4)	2 (0.8)	1.46 (0.27-8.03)
Bone, articular cartilage, connective, and other soft tissue	0	3 (1.2)	-	2 (0.2)	2 (0.8)	2.85 (0.40-20.24)
Melanoma	0	1 (0.4)	-	0	3 (1.2)	-
Breast	0	0	-	6 (0.6)	5 (2.0)	2.58 (0.79-8.50)
Genital	10 (1.0)	2 (0.8)	0.76 (0.16-3.53)	6 (0.6)	1 (0.4)	0.54 (0.06-4.49)
Genitourinary organs	7 (0.7)	7 (2.8)	3.51 (1.21-10.17)	2 (0.2)	2 (0.8)	3.21 (0.45-22.98)
Prostate	9 (0.9)	2 (0.8)	0.86 (0.18-4.06)	-	-	-
Eyes	0	1 (0.4)	-	0	1 (0.4)	-
Brain and nervous system	0	0	-	1 (0.1)	0	-
Thyroid gland and endocrine glands	2 (0.2)	0	-	1 (0.1)	0	-
Lymphatic and hematopoietic tissue	5 (0.5)	1 (0.4)	0.7 (0.08-6.12)	2 (0.2)	0	-

Table 1. Characteristics and potential confounders of the study subjects

Values are presented as number (%) or mean±standard deviation.

Table 2. Risk of second primary cancer in people with non-melanoma skin cancer

HR, hazard ratio; CI, confidence interval; NMSC, non-melanoma skin cancer.

Adjusted for age, sex, urbanization, and Charlson Comorbidity Index.

Table 3. Stratified analysis based on sex

NMSC, non-melanoma skin cancer; HR, hazard ratio; CI, confidence interval.

Adjusted for age, sex, urbanization, and Charlson Comorbidity Index.