Person:

Han, Jiali

Background: 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). Conclusion: 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

Background: Xeroderma pigmentosum complementation group F (XPF or ERCC4) plays a key role in DNA repair that protects against genetic instability and carcinogenesis. A series of epidemiological studies have examined associations between XPF polymorphisms and cancer risk, but the findings remain inconclusive. Methodology/Principal Findings: In this meta-analysis of 47,639 cancer cases and 51,915 controls, by searching three electronic databases (i.e., MEDLINE, EMBASE and CNKI), we summarized 43 case-control studies from 29 publications on four commonly studied polymorphisms of XPF (i.e., rs1800067, rs1799801, rs2020955 and rs744154), and we did not find statistical evidence of any significant association with overall cancer risk. However, in stratification analyses, we found a significant association of XPF-rs1799801 with a reduced cancer risk in Caucasian populations (4,845 cases and 5,556 controls; recessive model: OR = 0.87, 95% CI = 0.76–1.00, P = 0.049, P = 0.723 for heterogeneity test, I2 = 0). Further genotype-phenotype correlation analysis showed that the homozygous variant CC genotype carriers had higher XPF expression levels than that of the TT genotype carriers (Student’s t test for a recessive model: P = 0.046). No publication bias was found by using the funnel plot and Egger’s test. Conclusion: This meta-analysis suggests a lack of statistical evidence for the association between the four XPF SNPs and overall risk of cancers. However, XPF-rs1799801 may be associated with cancer risk in Caucasian populations, which needs to be further validated in single large, well-designed prospective studies.

Background: Cutaneous nevi are suggested to be hormone-related. We hypothesized that the number of cutaneous nevi might be a phenotypic marker of plasma hormone levels and predict subsequent breast cancer risk. Methods and Findings: We followed 74,523 female nurses for 24 y (1986–2010) in the Nurses' Health Study and estimate the relative risk of breast cancer according to the number of cutaneous nevi. We adjusted for the known breast cancer risk factors in the models. During follow-up, a total of 5,483 invasive breast cancer cases were diagnosed. Compared to women with no nevi, women with more cutaneous nevi had higher risks of breast cancer (multivariable-adjusted hazard ratio, 1.04, 95% confidence interval [CI], 0.98–1.10 for 1–5 nevi; 1.15, 95% CI, 1.00–1.31 for 6–14 nevi, and 1.35, 95% CI, 1.04–1.74 for 15 or more nevi; p for continuous trend = 0.003). Over 24 y of follow-up, the absolute risk of developing breast cancer increased from 8.48% for women without cutaneous nevi to 8.82% (95% CI, 8.31%–9.33%) for women with 1–5 nevi, 9.75% (95% CI, 8.48%–11.11%) for women with 6–14 nevi, and 11.4% (95% CI, 8.82%–14.76%) for women with 15 or more nevi. The number of cutaneous nevi was associated with increased risk of breast cancer only among estrogen receptor (ER)–positive tumors (multivariable-adjusted hazard ratio per five nevi, 1.09, 95% CI, 1.02–1.16 for ER+/progesterone receptor [PR]–positive tumors; 1.08, 95% CI, 0.94–1.24 for ER+/PR− tumors; and 0.99, 95% CI, 0.86–1.15 for ER−/PR− tumors). Additionally, we tested plasma hormone levels according to the number of cutaneous nevi among a subgroup of postmenopausal women without postmenopausal hormone use (n = 611). Postmenopausal women with six or more nevi had a 45.5% higher level of free estradiol and a 47.4% higher level of free testosterone compared to those with no nevi (p for trend = 0.001 for both). Among a subgroup of 362 breast cancer cases and 611 matched controls with plasma hormone measurements, the multivariable-adjusted odds ratio for every five nevi attenuated from 1.25 (95% CI, 0.89–1.74) to 1.16 (95% CI, 0.83–1.64) after adjusting for plasma hormone levels. Key limitations in this study are that cutaneous nevi were self-counted in our cohort and that the study was conducted in white individuals, and thus the findings do not necessarily apply to other populations. Conclusions: Our results suggest that the number of cutaneous nevi may reflect plasma hormone levels and predict breast cancer risk independently of previously known factors. Please see later in the article for the Editors' Summary