Increased Risk Of Basal Cell Carcinoma Research Articles

Exposome and basal cell carcinoma: a multicenter case-control study.

While ultraviolet radiation (UVR) present in sunlight is recognized as the main etiological agent of skin cancer, the most frequent form of which is basal cell carcinoma (BCC), other exposome factors like pollution, diet, and lifestyle may also contribute. This study aimed to investigate the association of BCC and exposome-related factors in the Spanish population. BCC cases (n = 119) and controls (n = 127) with no history of skin cancer were recruited between April 2020 and August 2022 by 13 dermatologists throughout Spain in this prospective multicenter case-control study. The BCC group had a higher proportion of outdoor workers, more years of UVR exposure, and a greater consumption of drugs (statins, ASA, hydrochlorothiazide, ACE inhibitors and omeprazole), P < 0.05. Avoidance of sun exposure was the most used photoprotection measure in both groups. The use of hats or caps was higher in the BCC group (P = 0.01). The solar protection factor (SPF) used 15 years previously was higher in the control group (P = 0.04). The control group had a higher daily screen time (P < 0.001), and practiced more relaxation activities (P = 0.03). Higher linolenic acid intake and lower coffee consumption were the only dietary variables associated with BCC (P < 0.05). Statistical significance for all the aforementioned variables was maintained in the multivariate analysis (P < 0.05). The study found a significant association between BCC and multiple exposome-related factors in addition to chronic sunexposure in the Spanish population. Primary prevention strategies should target specific populations, such as outdoor workers, promoting sun-safe behaviors and stress-reducing activities, and also adequate skin photoprotection in patients on certain medications associated with increased BCC risk.

Polyunsaturated Fatty Acid Levels and the Risk of Keratinocyte Cancer: A Mendelian Randomization Analysis.

Keratinocyte cancer is the commonest cancer, imposing a high economic burden on the health care system. Observational studies have shown mixed associations between polyunsaturated fatty acids (PUFA) and keratinocyte cancer, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). We explored whether genetically predicted PUFA levels are associated with BCC and SCC risks. We conducted a two-sample Mendelian randomization study using PUFA level genome-wide association studies (GWAS) from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (n > 8,000), and the meta-analysis GWASs from UKB, 23andMe, and Qskin for BCC (n = 651,138) and SCC (n = 635,331) risk. One SD increase in genetically predicted levels of linoleic acid [OR = 0.94, 95% confidence interval (CI) = 0.91-0.97, P = 1.4 × 10-4] and alpha-linolenic acid (OR = 0.91, 95% CI = 0.86-0.96, P = 5.1 × 10-4) was associated with a reduced BCC risk, while arachidonic acid (OR = 1.04, 95% CI = 1.02-1.06, P = 3.2 × 10-4) and eicosapentaenoic acid (OR = 1.10, 95% CI = 1.04-1.16, P = 1.5 × 10-3) were associated with an increased BCC risk. Higher genetically predicted levels of linoleic acid and alpha-linolenic acid were associated with a reduced BCC risk, but arachidonic acid and eicosapentaenoic acid were associated with a higher BCC risk. PUFA-related diet and supplementation could influence BCC etiology.

Common genetic polymorphisms contribute to the association between chronic lymphocytic leukaemia and non-melanoma skin cancer.

Epidemiological studies have demonstrated a positive association between chronic lymphocytic leukaemia (CLL) and non-melanoma skin cancer (NMSC). We hypothesized that shared genetic risk factors between CLL and NMSC could contribute to the association observed between these diseases. We examined the association between (i) established NMSC susceptibility loci and CLL risk in a meta-analysis including 3100 CLL cases and 7667 controls and (ii) established CLL loci and NMSC risk in a study of 4242 basal cell carcinoma (BCC) cases, 825 squamous cell carcinoma (SCC) cases and 12802 controls. Polygenic risk scores (PRS) for CLL, BCC and SCC were constructed using established loci. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Higher CLL-PRS was associated with increased BCC risk (OR4th-quartile-vs-1st-quartile = 1.13, 95% CI: 1.02-1.24, Ptrend = 0.009), even after removing the shared 6p25.3 locus. No association was observed with BCC-PRS and CLL risk (Ptrend = 0.68). These findings support a contributory role for CLL in BCC risk, but not for BCC in CLL risk. Increased CLL risk was observed with higher SCC-PRS (OR4th-quartile-vs-1st-quartile = 1.22, 95% CI: 1.08-1.38, Ptrend = 1.36 × 10-5), which was driven by shared genetic susceptibility at the 6p25.3 locus. These findings highlight the role of pleiotropy regarding the pathogenesis of CLL and NMSC and shows that a single pleiotropic locus, 6p25.3, drives the observed association between genetic susceptibility to SCC and increased CLL risk. The study also provides evidence that genetic susceptibility for CLL increases BCC risk.

Intake of Furocoumarins and Risk of Skin Cancer in 2 Prospective US Cohort Studies

In prior studies, higher citrus consumption was associated with higher risk of cutaneous malignant melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC). Furocoumarins, compounds with phototoxicity and photocarcinogenicity in citrus, may be responsible for the association. The objective of the study was to investigate the association between furocoumarin intake and skin cancer risk. A total of 47,453 men from the Health Professionals Follow-Up Study (HPFS) and 75,291 women from the Nurses' Health Study (NHS) with diet data collected every 2-4 y in the 2 prospective cohort studies were included. A furocoumarin food composition database for 7 common furocoumarins [bergaptol, psoralen, 8-methoxypsoralen, bergapten, 6',7'-dihydroxybergamottin (6'7'-DHB), epoxybergamottin, and bergamottin] was developed and used to calculate participants' cumulative average and energy-adjusted furocoumarin intake. Multivariate HRs and 95% CIs of the associations between furocoumarin intake and skin cancer risk were estimated using Cox proportional hazards models. Analyses were performed separately in each cohort as well as pooled using a fixed-effects model. Throughout follow-up (1984-2012 in the NHS and 1986-2012 in the HPFS), we identified 1593 melanoma, 4066 SCC, and 28,630 BCC cases. Higher intake of total furocoumarins was associated with an increased risk of BCC; the pooled HR comparing the top with the bottom quintile was 1.16 (95% CI: 1.11, 1.21; P-trend=0.002). Higher intakes of bergaptol, bergapten, 6'7'-DHB, and bergamottin were also significantly associated with increased BCC risk. No significant associations were found between intake of total furocoumarins and the risks of SCC or melanoma. Intakes of total furocoumarins as well as some individual furocoumarins were associated with an increased risk of skin cancer, especially BCC, in 2 cohorts of US health professionals.

496 STAT3 polymorphisms and IL-6 polymorphism are associated with the risk of basal cell carcinoma in patients from northern Poland

Basal cell carcinoma (BCC) environment consists of stromal and inflammatory cells which produce variety of cytokines, chemokines and growth factors that may affect the tumor behavior. One of the cytokines suggested to be involved in the pathogenesis of BCC is IL-6 - the upstream element of IL-6/JAK/STAT3 pathway. In the present study rs1800795 (-174 G/C) IL-6 gene polymorphism and STAT3 rs2293152 (intron 11, C/G) and rs4796793 (–1697, C/G) polymorphisms were assessed in relation to the BCC risk and clinical course. Additionally, IL-6 serum level was assessed in relation to IL-6 genotype and clinical variables. The study included 254 unrelated BCC patients (mean age 70.39±11.43) and 198 healthy, unrelated age- and sex-matched volunteers. We have found that the presence of C allele in rs1800795 IL-6 gene polymorphism was associated with increased risk of BCC (aOR: 1.86; 95% CI=1.22-2.84; p=0.004). The presence of CC genotype in STAT3 rs2293152 polymorphism was associated with increased BCC risk in recessive model analysis (aOR=3.94; 95% CI: 1.59-9.77; p=0.003). In contrast, the presence of GC genotype in overdominant model was associated with decreased risk of BCC (aOR=0.24; 95% CI:0.12-0.49; p<0.0001). The presence of C allele in STAT3 rs2293152 polymorphism was associated with increased risk of BCC (aOR: 1.31; 95% CI:1.01-1.69; p=0.04). The presence of GG genotype in STAT3 rs4796793 polymorphism was associated with increased BCC risk in recessive model analysis (aOR=3.66; 95% CI:1.33-10.10; p=0.012). The presence of G allele in STAT3 rs4796793 polymorphism was associated with increased risk of BCC (aOR: 1.59; 95% CI: 1.01-2.49; p=0.04). IL-6 serum level positively correlated with the tumor size.

119 Cyclooxygenase-2 Inhibitor Use and Risk of Skin Cancer: Three Prospective Cohort Studies

Cyclooxygenase-2 (COX-2) inhibitor has been associated with lower risk of several cancers, but epidemiological studies on skin cancer risk have been limited and inconclusive. COX-2 inhibitor use and risk of basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and melanoma were evaluated in three prospective cohorts - the Nurses’ Health Study (NHS, 2000-2012), NHS II (2001-2011), and the Health Professionals Follow-up Study (HPFS, 2002-2012). COX-2 inhibitor use and skin cancer incidence were assessed using biennial questionnaires, with cSCC and melanoma cases verified by pathological records. A total of 16,098 BCC, 1,973 cSCC, and 625 melanoma cases were documented in these three cohorts. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models. After pooling the three cohorts, we found that for ever versus never users, COX-2 inhibitor use was associated with increased BCC risk with multivariable HR 1.10 (95% CI 1.06—1.15). No significant association was found for cSCC or melanoma, although the HRs were similar to that of BCC, with multivariable HR 1.12 (95% CI 0.99—1.26) for cSCC and 1.10 (95% CI 0.89—1.38) for melanoma. COX-2 inhibitor use was associated with modest increased risk of BCC in these cohorts of Caucasian health professionals. Limitations include a homogenous population with restricted generalizability, self-reported use of medications, and relatively short follow-up duration. Further long-term investigation in other populations are needed to replicate these results.

STAT3 polymorphisms and IL-6 polymorphism are associated with the risk of basal cell carcinoma in patients from northern Poland

Basal cell carcinoma (BCC) environment consists of stromal and inflammatory cells which produce variety of cytokines, chemokines and growth factors that may affect tumor behavior. One of the cytokines suggested to be involved in the pathogenesis of BCC is IL-6, which is the upstream element of IL-6/JAK/STAT3 pathway. The correlation between polymorphisms of the genes related to this pathway and cancer risk/prognosis have been previously investigated in several neoplasia, but available data concerning BCC are scarce. In the present study, rs1800795 (-174 G/C) IL-6 gene polymorphism and two polymorphisms in the STAT3 gene, namely rs2293152 (intron 11, C/G) and rs4796793 (-1697, C/G) were assessed in relation to the BCC risk and clinical course. Additionally, IL-6 serum level was assessed in relation to IL-6 genotype and clinical variables. The study included 254 unrelated patients with BCC and of mean age 70.39 ± 11.43 (69.83 ± 12.32 women, 71.03 ± 10.31 men) and 198 healthy, unrelated age- and sex-matched volunteers. IL-6 and STAT3 polymorphisms were analyzed using polymerase chain reaction with sequence-specific primers (SSP-PCR). Serum concentration of IL-6 was measured using the ELISA test. We have found that the presence of C allele in rs1800795 IL-6 gene polymorphism was associated with increased risk of BCC (aOR 1.86; 95% CI 1.22–2.84; p = 0.004). The presence of CC genotype in STAT3 rs2293152 polymorphism was associated with increased BCC risk in recessive model analysis (aOR 3.94; 95% CI 1.59–9.77; p = 0.003). In contrast, the presence of GC genotype in overdominant model was associated with decreased risk of BCC (aOR = 0.24; 95% CI 0.12–0.49; p < 0.0001). The presence of C allele in STAT3 rs2293152 polymorphism was associated with increased risk of BCC (aOR 1.31; 95% CI 1.01–1.69; p = 0.04). The presence of GG genotype in STAT3 rs4796793 polymorphism was associated with increased BCC risk in recessive model analysis (aOR 3.66; 95% CI 1.33–10.10; p = 0.012). The presence of G allele in STAT3 rs4796793 polymorphism was associated with increased risk of BCC (aOR 1.59; 95% CI 1.01–2.49; p = 0.04). IL-6 serum level positively correlated with the tumor size.

Telomere length, arsenic exposure and risk of basal cell carcinoma of skin.

Telomere length per se a heritable trait has been reported to be associated with different diseases including cancers. In this study, based on arsenic-exposed 528 cases with basal cell carcinoma (BCC) of skin and 533 healthy controls, we investigated effect of telomere length, measured by real-time PCR, on the disease risk. We observed a statistically significant association between decreased telomere length and increased BCC risk [odds ratio (OR) = 5.92, 95% confidence interval (CI) = 3.92 to 9.01, P < 0.0001]. Due to confounder effect of arsenic exposure, in a two-sample Mendelian randomization (MR), telomere length associated single-nucleotide polymorphisms as instrument variables violated valid assumptions; however, one-sample MR adjusted for arsenic exposure indicated an increased risk of BCC with short telomeres. The interaction between arsenic exposure and telomere length on BCC risk was statistically significant (P = 0.02). Within each tertile based on arsenic exposure, the individuals with shorter telomeres were at an increased risk of BCC, with highest risk being in the highest exposed group (OR = 16.13, 95% CI = 6.71 to 40.00, P < 0.0001), followed by those in medium exposure group and low exposure group. The combined effect of highest arsenic exposure and shortest telomeres on BCC risk (OR = 10.56, 95% CI = 5.14 to 21.70) showed a statistically significant departure from additivity (interaction contrast ratio 6.56, P = 0.03). Our results show that in the presence of arsenic exposure, decreased telomere length predisposes individuals to increased risk of BCC, with the effect being synergistic in individuals with highest arsenic exposure and shortest telomeres.

Are phosphodiesterase type 5 inhibitors associated with increased risk of melanoma?: A systematic review and meta-analysis.

Phosphodiesterase type 5 (PDE5) inhibitors are recommended for patients with erectile dysfunction by American Urological Association and European Association Urology guidelines. However, recent researches have shown that PDE5 inhibitors may lead to increased melanoma risk. Thus, we aimed to explore whether PDE5 inhibitors are associated with increased melanoma risk based on published literatures.We conducted a systematic online search on PubMed, EMBASE, Cochrane Library, Chinese Biochemical Literature, China National Knowledge Infrastructure, and Chinese Science and Technology Periodical databases to identify the related studies. Odds ratios (ORs), risk ratios, and hazard ratios with 95% confidence intervals (CIs) were extracted and calculated to assess the strength of associations between PDE5 inhibitors and melanoma risk. We also extracted the basal cell carcinoma (BCC) to validate the association in this study.We included 5 studies containing 100,932 participants in our systematic review and meta-analysis. The calculated results suggested positive results of PDE5 inhibitors on melanoma risk (OR: 1.13; 95%CI: 1.04–1.23). For localized and nonlocalized melanoma, the results were different (OR: 1.22; 95%CI: 1.04–1.43 for localized melanoma) (OR: 0.62; 95%CI: 0.39–0.98 for nonlocalized melanoma). It also showed that PDE5 inhibitors were associated with increased BCC risk (OR: 1.18; 95%CI: 1.11–1.27).The association between PDE5 inhibitors and melanoma might not be causal due to potential bias (patient selection, and so on) and limitations.

Early Life UV and Risk of Basal and Squamous Cell Carcinoma in New South Wales, Australia.

Sun exposure is the main cause of squamous (SCC) and basal cell carcinoma (BCC) although pattern and amount differ by cancer type, and sun sensitivity is the major host risk factor. Our study investigated risk factors and residential ambient UV in a population-based sample of Australian 45 and Up Study participants: 916 BCC cases, 433 SCC cases, 1224 controls. Unconditional logistic regression models adjusting for key covariates demonstrated 60% increased BCC risk and two-fold increased SCC risk with sun sensitivity, and three- and four-fold increased risk, respectively, with solar keratoses. BCC but not SCC risk increased with higher early-life residential UV in all participants (odds ratio (OR) = 1.54; 95% CI 1.22-1.96 for intermediate; OR = 1.31; 95% CI 1.03-1.68 for high UV at birthplace) and similarly in Australian-born participants (P-values < 0.05). Risk of SCC but not BCC increased with long-term cumulative sun exposure assessed by self-reported outdoor work (OR 1.74, 95% CI 1.21-2.49). In conclusion, sun sensitivity is important for both cancers, early-life UV but not cumulative UV appears to increase BCC risk, the former an apparently novel finding, and SCC risk appears only to be related to long-term cumulative sun exposure.

Female Estrogen-Related Factors and Incidence of Basal Cell Carcinoma in a Nationwide US Cohort.

PurposeUV radiation exposure is the primary risk factor for basal cell carcinoma (BCC), the most common human malignancy. Although the photosensitizing properties of estrogens have been recognized for decades, few studies have examined the relationship between reproductive factors or exogenous estrogen use and BCC.MethodsUsing data from the US Radiologic Technologists Study, a large, nationwide, prospective cohort, we assessed the relationship between reproductive factors, exogenous estrogen use, and first primary BCC while accounting for sun exposure, personal sun sensitivity, and lifestyle factors for geographically dispersed women exposed to a wide range of ambient UV radiation.ResultsElevated risk of BCC was associated with late age at natural menopause (hazard ratio [HR] for ≥ 55 years v 50 to 54 years, 1.50; 95% CI, 1.04 to 2.17) and any use of menopausal hormone therapy (MHT; HR, 1.16; 95% CI, 1.03 to 1.30; P for trend for duration = .001). BCC risk was most increased among women reporting natural menopause who used MHT for 10 or more years versus women who never used MHT (HR, 1.97; 95% CI, 1.35 to 2.87). Risk of BCC was not associated with age at menarche, parity, age at first birth, infertility, use of diethylstilbestrol by participant's mother, age at hysterectomy, or use of oral contraceptives.ConclusionThese analyses confirm a previous finding of increased risk of BCC associated with MHT. Novel findings of increased BCC risk associated with MHT in women experiencing natural menopause and for late age at natural menopause warrant further investigation. Users of MHT may constitute an additional high-risk group in need of more frequent skin cancer screening.

Alcohol consumption and risk of cutaneous basal cell carcinoma in women and men: 3 prospective cohort studies

Alcohol consumption has been associated with an increased prevalence of sunburn, which is an established skin cancer risk factor. We investigated whether alcohol consumption is associated with risk of cutaneous basal cell carcinoma (BCC). We conducted a prospective analysis on alcohol consumption and risk of BCC on the basis of data from 167,765 women in the NHS (Nurses' Health Study) (1984-2010) and NHS II (1991-2011) and 43,697 men in the Health Professionals Follow-Up Study (1986-2010). Alcohol intake was repeatedly assessed every 2-4 y over the follow-up period. HRs and 95% CIs for BCC in association with alcohol intake were computed with the use of Cox proportional hazards models with adjustment for sun exposure and other skin cancer risk factors. A total of 28,951 incident BCC cases were documented over 3.74 million person-years of follow-up. Increased alcohol intake was associated with increased BCC risk in both women and men (both P-trend < 0.0001). Pooled multivariable-adjusted HRs over increasing cumulative averaged alcohol intake categories were 1.00 (reference) for nondrinkers, 1.13 (95% CI: 1.06, 1.20) for 0.1-9.9 g/d, 1.24 (95% CI: 1.14, 1.35) for 10.0-19.9 g/d, 1.27 (95% CI: 1.20, 1.35) for 20.0-29.9 g/d, and 1.22 (95% CI: 1.15, 1.30) for ≥30.0 g/d (P-trend < 0.0001, P-heterogeneity by study = 0.10 ). The association remained consistent when we used alcohol intakes over different latency periods (0-4, 4-8, 8-12, and 12-16 y) as exposures and over categories of sun exposure-related factors. In the individual alcoholic beverages, white wine and liquor were positively associated with BCC risk. Alcohol consumption is associated with increased risk of cutaneous BCC in both women and men.

Intake of Alcohol May Modify the Risk for Non-Melanoma Skin Cancer: Results of a Large Danish Prospective Cohort Study

Alcohol has not been linked definitively to non-melanoma skin cancer. We examined whether alcohol intake affects the risks for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) using data on 54,766 persons enrolled in the prospective Diet, Cancer, and Health cohort. Statistical analyses were based on the Cox proportional hazards model. All hazard ratios (HRs) were multivariate adjusted. Adjustment for exposure to UVR was not possible, but all analyses were adjusted for factors related to susceptibility to UVR, including sun sensitivity, degree of freckling, and number of nevi. A total of 2,409 BCC cases and 198 SCC cases were diagnosed within a median follow-up of 11.4 years. Total current alcohol intake was not associated with BCC risk, but beverage-specific analyses showed an increased BCC risk associated with intake of wine (HR=1.05, 95% confidence interval (CI): 1.02-1.08, current average alcohol intake, per 10 g per day) and spirits (HR=1.11, 95% CI: 1.02-1.21) and a decreased risk with beer (HR=0.97, 95% CI: 0.93-1.00). No convincing associations were found between total alcohol intake and risk for SCC, perhaps because of the limited number of cases. Our findings indicate that alcohol intake may increase the risk for BCC, but the relations seemed to depend on beverage type.

PTCH1 gene haplotype association with basal cell carcinoma after transplantation

Basal cell carcinoma (BCC) is 10 times more frequent in organ transplant recipients (OTRs) than in the general population. Factors in OTRs conferring increased susceptibility to BCC include ultraviolet radiation exposure, immunosuppression, viral infections such as human papillomavirus, phototype and genetic predisposition. The PTCH1 gene is a negative regulator of the hedgehog pathway, that provides mitogenic signals to basal cells in skin. PTCH1 gene mutations cause naevoid BCC syndrome, and contribute to the development of sporadic BCC and other types of cancers. Associations have been reported between PTCH1 polymorphisms and BCC susceptibility in nontransplanted individuals. To search for novel common polymorphisms in the proximal 5' regulatory region upstream of PTCH1 gene exon 1B, and to investigate the possible association of PTCH1 polymorphisms and haplotypes with BCC risk after organ transplantation. Three PTCH1 single nucleotide polymorphisms (rs2297086, rs2066836 and rs357564) were analysed by restriction fragment length polymorphism analysis in 161 northern Italian OTRs (56 BCC cases and 105 controls). Two regions of the PTCH1 gene promoter were screened by heteroduplex analysis in 30 cases and 30 controls. Single locus analysis showed no significant association. Haplotype T(1686)-T(3944) appeared to confer a significantly higher risk for BCC development (odds ratio 2.98, 95% confidence interval 2.55-3.48; P = 0.001). Two novel rare polymorphisms were identified at positions 176 and 179 of the 5'UTR. Two novel alleles of the -4 (CGG)(n) microsatellite were identified. No association of this microsatellite with BCC was observed. Haplotypes containing T(1686)-T(3944) alleles were shown to be associated with an increased BCC risk in our study population. These data appear to be of great interest for further investigations in a larger group of transplant individuals. Our results do not support the hypothesis that common polymorphisms in the proximal 5' regulatory region of the PTCH1 gene could represent an important risk factor for BCC after organ transplantation.

A comparison of sunlight exposure in men with prostate cancer and basal cell carcinoma

Ultraviolet radiation exposure increases basal cell carcinoma (BCC) risk, but may be protective against prostate cancer. We attempted to identify exposure patterns that confer reduced prostate cancer risk without increasing that of BCC. We used a questionnaire to assess exposure in 528 prostate cancer patients and 442 men with basal cell carcinoma, using 365 benign prostatic hypertrophy patients as controls. Skin type 1 (odds ratio (OR)=0.47, 95% CI=0.26–0.86), childhood sunburning (OR=0.38, 95% CI=0.26–0.57), occasional/frequent sunbathing (OR=0.21, 95% CI=0.14–0.31), lifetime weekday (OR=0.85, 95% CI=0.80–0.91) and weekend exposure (OR=0.79, 95% CI=0.73–0.86) were associated with reduced prostate cancer risk. Skin type 1 (OR=4.00, 95% CI=2.16–7.41), childhood sunburning (OR=1.91, 95% CI=1.36–2.68), regular foreign holidays (OR=6.91, 95% CI=5.00-9.55) and weekend (OR=1.17, 95% CI=1.08–1.27) but not weekday exposure were linked with increased BCC risk. Combinations of one or two parameters were associated with a progressive decrease in the ORs for prostate cancer risk (OR=0.54–0.25) with correspondingly increased BCC risk (OR=1.60–2.54). Our data do not define exposure patterns that reduce prostate cancer risk without increasing BCC risk.

Polymorphisms in DNA double-strand break repair genes and skin cancer risk.

UV can cause a wide range of DNA lesions. UVA-induced oxidative DNA damage and blocked DNA replication by UVB-induced photoproducts can lead to double-strand breaks (DSBs). We selected 11 haplotype-tagging single nucleotide polymorphisms in three DSB repair genes XRCC2, XRCC3, and LigaseIV and evaluated their associations with skin cancer risk in a nested case-control study within the Nurses' Health Study [219 melanoma, 286 squamous cell carcinoma (SCC), 300 basal cell carcinoma (BCC), and 873 controls]. We observed that the XRCC3 18085T (241Met) allele and its associated haplotype were significantly inversely associated with the risks of SCC and BCC, whereas the XRCC3 4552C allele along with its associated haplotype and the XRCC2 30833A allele were significantly associated with increased BCC risk. The LigaseIV 4044T and 4062T alleles were associated with decreased BCC risk; two of four haplotypes were significantly associated with altered BCC risk. A trend toward decreased risk of nonmelanoma skin cancer was found in those harboring a greater number of putative low risk alleles (P for trend, 0.05 for SCC, <0.0001 for BCC). The main effects of these genotypes were essentially null for melanoma risk. This study provides evidence to suggest the role of the DSB repair pathway in skin cancer development, especially for BCC.