LEAD ARTICLE Familial Occurrence of Multiple Nonmelanoma Skin Cancer D. Czarnecki, J. Zalcberg, C. Meehan, T. O'Brien, S. Leahy, A. Bankier, and C. G. Nash

ABSTRACT: A survey of patients with histologically confirmed n o n m e l a n o m a skin cancer (NMSC) f o u n d 12 f a m i l i e s in w h i c h several members developed skin cancers. The prevalence of NMSC in these f a m i l i e s was far greater than in the n o r m a l population. The trait appeared to be d o m i n a n t l y inherited, and NMSC developed at an earlier age in succeeding generations, possibly because of a change in sun exposure habits.

INTRODUCTION

MATERIALS AND METHODS

Skin cancer is a major public health p r o b l e m in Australia. The i n c i d e n c e of n o n m e l a n o m a skin cancer (NMSC) is at least 850 per 100,000 in the temperate south [1] and 1560 per 100,000 in the subtropical north [2]. Exposure to sunlight has been l i n k e d to the d e v e l o p m e n t of basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) for more than 100 years [3]. However, not all people exposed to the sun will develop skin cancer. Those most at risk are those w h o s u n b u r n easily and tan poorly, i.e., those with a fair c o m p l e x i o n [4-6]. Light eye color correlates better with a fair c o m p l e x i o n than does hair color [4, 5, 7, 8]. The role of h e r e d i t y in the d e v e l o p m e n t of nonmelan o m a skin cancer is not clear. Some authors have treated more than one m e m b e r of a family for skin cancer and have suggested that h e r e d i t y m a y be important [4, 8, 9, 10]. This has been d i s m i s s e d b y others, who felt that heredity plays an indirect role, by virtue of inherited c o m p l e x i o n or Celtic ancestry [11]. The Celts are particularly susceptible to develop skin cancer, even in areas of low-intensity ultraviolet light [12, 13]. We report on 12 families in w h i c h more than one member has had one or more n o n m e i a n o m a skin c a n c e r s - - a pattern that appears to have been inherited as an autosoma] d o m i n a n t trait.

For the past 18 m o n t h s information has been collected on consecutive outpatients w i t h h i s t o l o g i c a l l y confirmed n o n m e l a n o m a skin cancers. The patients were asked about family members with skin cancer. Confirmation was obtained by examining the relative, or, w h e r e the relatives were deceased or unable to be e x a m i n e d , the diagnosis was confirmed by writing to the treating doctor or hospital. The eye color and ancestry of p e o p l e w i t h skin cancer was recorded. A m o n g the patients there were 12 families in w h o m more than one m e m b e r had a n o n m e l a n o m a skin cancer.

From the Repatriation General Hospital (D. C., J. Z., C. M., S. L.), Heidelberg, Victoria, Australia, Skin and Cancer Foundation (T. O'B., C. G. N.), Fitzroy, Victoria, Australia; Murdoch Institute (A. B.), Royal Children's Hospital, Flemington Road, Parkville, Victoria, Australia. Presented at the 3rd Winter Surgery Meeting Melbourne, August 3, 1991. Address reprint requests to: Dr. D. Czarnecki, Suite 1, 12 Floriston Road, Boronia, Victoria 3155, Australia. Received September 23, 1991; accepted November 25, 1991.

RESULTS All patients had lived the majority of their lives in Melbourne, located at 38 ° south, in the t e m p e r a t e zone of Australia. The details of 1,108 patients were r e c o r d e d [14] (see Table 1), and this s a m p l e represented a p p r o x i m a t e l y 3% of the skin cancer p o p u l a t i o n of Melbourne, based on the estimated prevalence of NMSC in M e l b o u r n e [15] and the estimated p o p u l a t i o n on June 30, 1989 (Australian Bureau of Statistics). Of the 1108 patients, 918 had d e v e l o p e d a BCC and 190 an SCC. The average age of patients w i t h a BCC was 63.9 years and for those with an SCC, 71.9 years. O n l y 110 (10%) were under the age of 40 years, and no one was younger than 15. M u l t i p l e skin cancers (3 or more) had d e v e l o p e d in 467 (42.1%)-during their lives. However, it was u n u s u a l for people aged less than 40 to d e v e l o p m u l t i p l e skin cancers, and only 22 (2%) of the patients in this age bracket had d e v e l o p e d 3 or more skin cancers. No one u n d e r the age of 40 had d e v e l o p e d an SCC.

FAMILY STUDIES (FAMILIES 1 - 6 ; FIG. 1) Family 1 The p r o b a n d (II-4) began to d e v e l o p skin cancers in his mid-50s, and more than 20 BCCs and SCCs h a d been re1

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Cancer Genet Cytogenet 61:1-5 0165-4608/92/$05.00

(1992)

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D. Czarnecki et el.

Table 1 A s u m m a r y of the survey of n o n m e l a n o m a skin cancer

Number

% of total survey

Age 40 or more Total Multiple cancers

997 447

90.0 40.3

Age 15-39 Total Multiple cancers

111 22

10.0 2.0

had one BCC removed in their late 40s, and her maternal grandfather (I-1) was treated for a skin cancer on the ear. The diagnosis was not confirmed histologically, but he was treated with radiotherapy. The family's ancestry was Scottish.

FAMILY STUDIES (FAMILIES 7-12, FIG. 2) Family 7

moved. His son (III-1) had 4 BCCs removed at the age of 36 and 4 more by the age of 38. The p r o b a n d ' s father (I-2) died of bowel cancer. The p r o b a n d ' s current age is 64, and the family's ancestry was m a i n l y Cornish.

Family 2 The p r o b a n d (II-3) suffered from skin cancer from his early 50s, and 10 SCCs had been removed by his current age of 65. His brother (II-1) and sister (II-5) had both had m a n y BCCs and SCCs removed since their early 50s. The proband's father (I-2) had been treated for solar keratoses (SKs), but there were no k n o w n skin cancers. The family's ancestry was English and Scottish. Family 3 The p r o b a n d (II-3) had had more than 20 BCCs removed since his early 60s. Three BCCs had been removed from his younger brother (II-5), and his older brother (II-1) had only had SKs removed. The p r o b a n d ' s father (I-1) had died from metastatic SCC of the skin at the age of 54, after several BCCs and SCCs had been treated previously. The p r o b a n d ' s current age is 73, and the family's ancestry was German and English.

Family 4 The first BCC was removed from the p r o b a n d (III-4) in her early 30s, and 8 BCCs had been removed by her current age of 38. Her older sister (III-3) had one BCC removed at the age of 40, and her older brother (III-1) had 3 BCCs removed before the age of 40. Both her father (II-1) and mother (II2), had several BCCs removed, as had her maternal grandmother (I-3). The family's ancestry was m i x e d Polish, Spanish, and Irish.

Family 5 The first BCC was r e m o v e d from the p r o b a n d (III-1) at the age of 31, and 12 BCCs been removed to date. Her sister (III°2) had one BCC removed at the age of 40. Her mother (II-3), uncle (II-1), and maternal grandfather (I-1) each had several BCCs removed. The grandfather had suffered from cancer of the prostate. The p r o b a n d ' s current age is 42, and the family's ancestry was a mixture of Welsh and Italian.

Family 6 The first BCC was removed from the p r o b a n d (III-1) at the age of 22, and five tumors had been r e m o v e d by her current age of 25 years. Both her father (II-2) and mother (II-3) had

The proband (II-1) started d e v e l o p i n g skin cancer in his late 50s, and more than 20 BCCs and SCCs had been r e m o v e d by his current age of 70 years. His brother (II-3) had been treated for skin cancer since his mid-50s, and several BCCs and SCCs had been removed or treated by radiotherapy. His sister (II-5) had suffered from cancer of the colon as well as having had several BCCs removed. Both of the p r o b a n d ' s sons had skin cancers r e m o v e d in their early 40s. A BCC had been removed from the older son (III-1) and an SCC from the younger son (III-2). The p r o b a n d ' s oldest n e p h e w (III-3) had been treated for SKs at the age of 40 years. The family's ancestry was a mixture of English, Welsh, and French.

Family 8 The proband [III-2) started d e v e l o p i n g BCCs in his mid40s, and six BCCs had been r e m o v e d to date. His mother (II-1) had had several BCCs, and 2 aunts (II-3 and II-5) had one BCC each. An aunt (II-4) had d i e d of lung cancer, and his maternal grandmother (I-1) had d i e d of breast cancer. His older brother (III-1) had had a m e l a n o m a removed, and his younger brother (III-3) had had a BCC removed. Neither the proband nor his siblings had any clinical evidence of dysplastic naevi. The p r o b a n d ' s current age is 62, and the ancestry is a mixture of Maltese, German, and Scottish.

Family 9 The p r o b a n d (II-2) had more than 20 BCCs, but no SCCs, removed by his current age of 47 years. Several BCCs had been removed from his sister (II-4), and his father (I-1) had both BCCs and SCCs removed. His father died of lung cancer and an older brother (II-1) had died of cancer. The family had drifted apart and details of illnesses in other members are unknown. The ancestry was m a i n l y Irish.

Family 10 The p r o b a n d (III-1) began d e v e l o p i n g BCCs in her early 40s, and 7 had been removed by her current age of 49 years. Her sister (III-2) had a m e l a n o m a removed at the age of 26 but had not had any other skin cancers removed. The p r o b a n d and her sister d i d not have any evidence of dysplastic naevi. The p r o b a n d ' s mother (II-2) started d e v e l o p i n g BCCs in her late 30s, and more than a d o z e n had been treated by her mid-60s. The p r o b a n d ' s maternal g r a n d m o t h e r (I-2) was treated for a BCC that was a clinical diagnosis. Her father (II-1) died of tuberculosis at an early age, and her two maternal uncles (IDa, II-4) d i e d of internal cancer. No members had d e v e l o p e d any SCCs, and the family's ancestry was German and Scottish.

F a m i l i a l M u l t i p l e N o n m e l a n o m a Skin Cancer

3

FAMILY I.

FAMILY 2.

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2

3

1

6

2

3

4

FAMILY 3.

FAMILY 4.

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3

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BCC was diagnosed

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Family pedigrees for families 1-6. See Figure 2 for legend.

Family 11

DISCUSSION

The p r o b a n d (III-2) d e v e l o p e d her first BCC at the age of 42, and three had been removed by her curent age of 45. Her older brother (III-1) and younger sister (II-3) had both had more than three BCCs removed by their mid-40s. The p r o b a n d ' s father (I-2) began to develop BCCs at the age of 45, and more than 20 had been removed. The p r o b a n d ' s aunt (I-5) and uncle (I-3) had died of internal cancer, and the ancestry was English and Scottish.

This study has identified 12 families in w h i c h more than one m e m b e r had d e v e l o p e d NMSC. In 11 families skin cancers had d e v e l o p e d in more than 1 generation, and in 9 of these, m u l t i p l e skin cancers had d e v e l o p e d in 2 or more generations. Most of the affected p e o p l e had d e v e l o p e d only BCCs, although there were m e m b e r s in the same family who had d e v e l o p e d both BCCs and SCCs, or only SCCs. The latter two groups were older than those who had only d e v e l o p e d BCCs. The younger, affected m e m b e r s of these families m a y develop SCCs in the future because the average age of p e o p l e with SCCs is 8 years older than those with BCCs in both the temperate and tropical zones of Australia [14]. Both m e n and w o m e n were affected but m e n o u t n u m bered women. More men than w o m e n d e v e l o p skin cancer

Family 12 The p r o b a n d (II-2) d e v e l o p e d a BCC at the age of 39, three more were removed by his current age of 42. father (I-3) began d e v e l o p i n g BCCs in his early 60s, more than 20 had been r e m o v e d by the age of 75. ancestry was Irish and English.

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D. Czarnecki et al. FAHILY 7. ,

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Familial occurrence of multiple nonmelanoma skin cancer.

A survey of patients with histologically confirmed nonmelanoma skin cancer (NMSC) found 12 families in which several members developed skin cancers. T...
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