Studies have suggested a positive association between history of non-melanoma skin cancer (NMSC) and risk of subsequent cancer at other sites. This prospective study found a modestly increased risk of subsequent malignancies among individuals with a history of NMSC, specifically breast and lung cancer in women and melanoma in both men and women.
Previous studies suggest a positive association between history of non-melanoma skin cancer (NMSC) and risk of subsequent cancer at other sites. The purpose of this study is to prospectively examine the risk of primary cancer according to personal history of NMSC.
Methods and Findings
In two large US cohorts, the Health Professionals Follow-up Study (HPFS) and the Nurses' Health Study (NHS), we prospectively investigated this association in self-identified white men and women. In the HPFS, we followed 46,237 men from June 1986 to June 2008 (833,496 person-years). In the NHS, we followed 107,339 women from June 1984 to June 2008 (2,116,178 person-years). We documented 29,447 incident cancer cases other than NMSC. Cox proportional hazard models were used to calculate relative risks (RRs) and 95% confidence intervals (CIs). A personal history of NMSC was significantly associated with a higher risk of other primary cancers excluding melanoma in men (RR = 1.11; 95% CI 1.05–1.18), and in women (RR = 1.20; 95% CI 1.15–1.25). Age-standardized absolute risk (AR) was 176 in men and 182 in women per 100,000 person-years. For individual cancer sites, after the Bonferroni correction for multiple comparisons (n = 28), in men, a personal history of NMSC was significantly associated with an increased risk of melanoma (RR = 1.99, AR = 116 per 100,000 person-years). In women, a personal history of NMSC was significantly associated with an increased risk of breast (RR = 1.19, AR = 87 per 100,000 person-years), lung (RR = 1.32, AR = 22 per 100,000 person-years), and melanoma (RR = 2.58, AR = 79 per 100,000 person-years).
This prospective study found a modestly increased risk of subsequent malignancies among individuals with a history of NMSC, specifically breast and lung cancer in women and melanoma in both men and women.
Please see later in the article for the Editors' Summary
In the United Kingdom and the United States, about one in three people develop cancer during their lifetime and, worldwide, cancer is responsible for 13% of all deaths. Primary cancer, which can develop anywhere in the body, occurs when a cell begins to divide uncontrollably because of alterations (mutations) in its genes. Additional mutations allow the malignancy to spread around the body (metastasize) and form secondary cancers. The mutations that initiate cancer can be triggered by exposure to carcinogens such as cigarette smoke (lung cancer) or the ultraviolet (UV) radiation in sunlight (skin cancers). Other risk factors for the development of cancer include an unhealthy diet, physical inactivity, and alcohol use. In the United States, the most common cancer is non-melanoma skin cancer (NMSC). Although more than 2 million new cases of NMSC occur each year, fewer than 1,000 people die annually in the United States from the condition because the two types of NMSC—basal cell carcinoma and squamous cell carcinoma—rarely metastasize and can usually be treated by surgically removing the tumor.
Why Was This Study Done?
Some studies have suggested that people who have had NMSC have a higher risk of developing primary cancer at other sites than people who have not had NMSC. Such a situation could arise if exposure to certain carcinogens initiates both NMSC and other cancers or if NMSC shares a molecular mechanism with other cancers such as a deficiency in the DNA repair mechanisms that normally remove mutations. If people with a history of NMSC are at a greater risk of developing further cancers, a specific surveillance program for such people might help to catch subsequent cancers early when they can be successfully treated. In this prospective cohort study, the researchers examine the risk of primary cancer according to personal history of NMSC in two large US cohorts (groups)—the Health Professionals Follow-up Study (HPFS) and the Nurses' Health Study (NHS). The HPFS, which enrolled 51,529 male health professionals in 1986, and the NHS, which enrolled 121,700 female nurses in 1976, were both designed to investigate associations between nutritional factors and the incidence of serious illnesses. Study participants completed a baseline questionnaire about their lifestyle, diet and medical history. This information is updated biennially through follow-up questionnaires.
What Did the Researchers Do and Find?
The researchers identified 36,102 new cases of NMSC and 29,447 new cases of other primary cancers from 1984 in white NHS participants and from 1986 in white HPFS participants through 2008. They then used statistical models to investigate whether a personal history of NMSC was associated with a higher risk of subsequent primary cancers after accounting for other factors (confounders) that might affect cancer risk. A history of NMSC was significantly associated with an 11% higher risk of other primary cancers excluding melanoma (another type of skin cancer that, like NMSC, is linked to overexposure to UV light) in men and a 20% higher risk of other primary cancers excluding melanoma in women; a significant association is one that is unlikely to have happened by chance. The absolute risk of a primary cancer among men and women with a history of NMSC was 176 and 182 per 100,000 person-years, respectively. For individual cancer sites, after correction for multiple comparisons (when several conditions are compared in groups of people, statistically significant differences between the groups can occur by chance), a history of NMSC was significantly associated with an increased risk of breast and lung cancer in women and of melanoma in men and women.
What Do These Findings Mean?
These findings suggest that there is a modestly increased risk of subsequent malignancies among white individuals with a history of NMSC. Although the researchers adjusted for many confounding lifestyle factors, the observed association between NMSC and subsequent primary cancers may nevertheless be the result of residual confounding, so it is still difficult to be sure that there is a real biological association (due to, for example, a deficiency in DNA repair) between NMSC and subsequent primary cancers. Because of this and other study limitations, the findings reported here should be interpreted cautiously and do not suggest that individuals who have had NMSC should undergo increased cancer surveillance. These findings do, however, support the need for continued investigation of the apparent relationship between NMSC and subsequent cancers.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001433.
The US National Cancer Institute provides information on all aspects of cancer and has detailed information about non-melanoma skin cancer for patients and professionals (in English and Spanish)
The non-profit organization American Cancer Society provides information on cancer and how it develops and specific information on skin cancer (in several languages); its website includes personal stories about cancer
The UK National Health Service Choices website includes an introduction to cancer and a page on non-melanoma skin cancer
The non-profit organization Cancer Research UK provides basic information about cancer and detailed information on non-melanoma skin cancer