Racial differences in the risk of second primary bladder cancer following radiation therapy among localized prostate cancer patients.

OBJECTIVES: To investigate the race-specific second primary bladder cancer (SPBC) risk following prostatic irradiation. METHODS: Louisiana residents who were diagnosed with localized prostate cancer (PCa) in 1996-2013 and received surgery or radiation were included. Patients were followed until SPBC diagnosis, death, or Dec. 2018. The exposure variable was type of treatment (radiation only vs. surgery only). The outcome was time from PCa diagnosis to SPBC diagnosis, stratified by race. Fine and Gray's competing risk model was applied with death as a competing event and adjustment of sociodemographic and tumor characteristics. We used 5 years and 10 years as lag time in the analyses. RESULTS: A total of 26,277 PCa patients with a median follow-up of 10.7 years were analyzed, including 18,598 white and 7679 black patients. About 42.9 % of whites and 45.7 % of blacks received radiation. SPBC counted for 1.84 % in the radiation group and 0.90 % in the surgery group among white patients and for 0.91 % and 0.58 %, respectively, among black patients. The adjusted subdistribution hazard ratio of SPBC was 1.80 (95 % CI: 1.30-2.48) for radiation recipients compared to surgery recipients among white patients; 1.93 (95 % CI: 1.36-2.74) if restricted to external beam radiation therapy (EBRT). The SPBC risk was not significantly different between irradiated and surgically treated among blacks. CONCLUSIONS: The SPBC risk is almost two-fold among white irradiated PCa patients compared to their counterparts treated surgically. Our findings highlight the need for enhanced surveillance for white PCa survivors receiving radiotherapy, especially those received EBRT.

Birth month and risk of skin tumors-Follow up of six million Caucasians born from 1950 to 2014 in Sweden.

BACKGROUND: Some studies hypothesize that birth month-as a proxy of exposure to ultraviolet radiation in early infancy-is associated with increased risk of skin tumors. METHODS: We studied a national cohort of all 5 874 607 individuals born in Sweden to parents of Swedish or Nordic origin as a proxy for Caucasian origin, 1950 to 2014. The cohort was followed for incident skin tumors, including squamous cell carcinomas and melanomas but not basal cell carcinomas, through 2015 from birth up to age 65 for the oldest cohort. Cox regression estimated the association between month of birth and risk of skin tumors in models adjusted for sex, calendar period, and education. Crude observed to expected ratios were also calculated. RESULTS: There were 33 914 cases of skin tumors, of these, 3025 were squamous cell cancer, 16 968 malignant melanoma and 8493 melanoma in situ/other and 5 428 squamous cell in situ/other in 192 840 593 person-years of follow-up. Observed to expected ratios by month of birth showed no association between month of birth and risk of skin tumors, and the same result was seen when Cox regression analysis was used. Subgroup analyses by sex, educational level, calendar period, or age at follow-up similarly showed no association. CONCLUSION: This large register-based cohort study showed no evidence of a higher risk of skin tumors in those born during the spring. Thus, this study lends no support to the hypothesis that birth during spring is a major risk factor for later skin tumors.

Melanoma Genomics.

The incidence of cutaneous melanoma continues to increase in pale skinned peoples in Europe and elsewhere. Epidemiological studies identified genetically determined phenotypes such as pale skin, freckles and red hair, and sunburn as risk factors for this cancer. The development of many melanocytic naevi is also genetically determined and a strong melanoma risk phenotype. Not surprisingly then, genome wide association studies have identified pigmentation genes as common risk genes, and to a lesser extent, genes associated with melanocytic naevi. More unexpectedly, genes associated with telomere length have also been identified as risk genes. Higher risk susceptibility genes have been identified, particularly CDKN2A as the most common cause, and very rarely genes such as CDK4, POT1, TERT and other genes in coding for proteins in the shelterin complex are found to be mutated. Familial melanoma genes are associated with an increased number of melanocytic naevi but not invariably and the atypical naevus phenotype is therefore an imperfect marker of gene carrier status. At a somatic level, the most common driver mutation is BRAF, second most common NRAS, third NF1 and increasing numbers of additional rarer mutations are being identified such as in TP53. It is of note that the BRAF and NRAS mutations are not C>T accepted as characteristic of ultraviolet light induced mutations.

Melanoma Epidemiology and Sun Exposure.

The worldwide incidence of melanoma has increased rapidly over the last 50 years. Melanoma is the most common cancer found in the young adult population, and its incidence is very high among geriatric populations. The incidence of melanoma varies by sex, and this factor is also associated with differences in the anatomical site melanoma. Adolescent and young adult women have a higher incidence than men. This may be, in part, due to the greater use of sunbeds, as well as intentional sun exposure among girls and, in general, risky behaviours in seeking to suntan, due to socially-determined aesthetic needs. Indeed, the World Health Organization declared that there is sufficient evidence to classify exposure to ultraviolet radiation (sunbed use and sun exposure) as carcinogenic to humans. Although pigmentation characteristics, such as skin colour, hair and eye colour, freckles and number of common and atypical naevi, do influence susceptibility to melanoma, recommendations regarding prevention should be directed to the entire population and should include avoiding sunbed, covering sun-exposed skin, wearing a hat and sunglasses. Sunscreen use should not be used to prolong intentional sun exposure. Primary prevention should be focused mainly on young adult women, while secondary prevention should be focused mainly on elderly men. In fact, after the age of 40 years, incidence rates reverse, and the incidence of melanoma among men is greater than among women. This is probably due to the fact that men are less likely than women to examine their own skin or present to a dermatologist for skin examination.

Echoes from the past- changing associations between brain tumors and ethnicity.

BACKGROUND: cranial X radiation therapy was the standard of care for treating dermatological conditions until the 1960s, when its association to cancer and particularly high rates of brain tumors was discovered. This study examines associations found between incidence of brain tumor and ethnicity. METHODS: This study analyzed two cohorts who underwent examination at age 17 and were followed by linkage to the national cancer registry. The first cohort included 376,336 participants born in 1948-1959 (when treatment with cranial X radiation was standard care for treating tinea capitis), and the second 474,923 participants born in 1960-1971. RESULTS: In the first cohort, ethnicity was strongly associated with the incidence of brain tumor (BT), with higher incidence observed among patients with origins in North Africa or the Middle East. This effect was ablated in the second cohort, and a significant decrease in the rate of meningiomas was noted. CONCLUSION: The association of brain tumor with ethnicity was present only during the period when treatment with cranial X radiation was the standard of care for TC in Israel, therefore it is most likely that radiation exposure was a confounding factor, and that ethnic susceptibility for brain cancer was not causative in these cohorts.

[Incidence of skin and non-skin cancers in Afro-Caribbean renal transplant recipients: Guadeloupe data from 2004 to 2011]. / Incidence des cancers cutanés et non cutanés chez les transplantés rénaux afro-caribéens : données guadeloupéennes de 2004 à 2011.

BACKGROUND: Cancer is the main complication of transplantation surgery. The literature concerning renal transplant recipients among the Afro-Caribbean population is scant. The aim of this study was to determine the incidence of cancer in these patients, with the secondary objective being to identify predisposing factors for cancer. PATIENTS AND METHODS: This was an epidemiological and retrospective study that included all Guadeloupians of phototype V-VI undergoing renal transplantation from 01/01/2004 to 31/12/2011. Skin cancer screening was performed before transplantation and during an annual dermatological consultation following transplantation. Screening for non-cutaneous cancers was guided by clinical symptoms or by the results of the screening examinations recommended in the current guidelines. At the study time-point (31/12/2011), all patients were examined by a dermatologist. RESULTS: One hundred and two patients were included : 42 women and 60 men (mean age: 52.1±11.6 years at transplantation). Eight cancers were diagnosed. The cumulative incidence of cancer was 7.8% at 3 years. Three factors were associated with more rapid onset of cancer: personal history or familial history of cancer, and genital lesion induced by HPV. CONCLUSION: Our results suggest a low incidence of cancer in Afro-Caribbean renal transplant patients. Personal or family history of cancer and HPV-induced genital lesions would appear to accelerate the onset of cancer in this population.

ETV6-NTRK3 is a common chromosomal rearrangement in radiation-associated thyroid cancer.

BACKGROUND: In their previous analysis of papillary thyroid carcinomas (PTCs) from an Ukrainian-American cohort that was exposed to iodine-131 ((131) I) from the Chernobyl accident, the authors identified RET/PTC rearrangements and other driver mutations in 60% of tumors. METHODS: In this study, the remaining mutation-negative tumors from that cohort were analyzed using RNA sequencing (RNA-Seq) and reverse transcriptase-polymerase chain reaction to identify novel chromosomal rearrangements and to characterize their relation with radiation dose. RESULTS: The ETS variant gene 6 (ETV6)-neurotrophin receptor 3 (NTRK3) rearrangement (ETV6-NTRK3) was identified by RNA-Seq in a tumor from a patient who received a high (131) I dose. Overall, the rearrangement was detected in 9 of 62 (14.5%) post-Chernobyl PTCs and in 3 of 151 (2%) sporadic PTCs (P = .019). The most common fusion type was between exon 4 of ETV6 and exon 14 of NTRK3. The prevalence of ETV6-NTRK3 rearrangement in post-Chernobyl PTCs was associated with increasing (131) I dose, albeit at borderline significance (P = .126). The group of rearrangement-positive PTCs (ETV6-NTRK3, RET/PTC, PAX8-PPARγ) was associated with significantly higher dose response compared with the group of PTCs with point mutations (BRAF, RAS; P < .001). In vitro exposure of human thyroid cells to 1 gray of (131) I and γ-radiation resulted in the formation of ETV6-NTRK3 rearrangement at a rate of 7.9 × 10(-6) cells and 3.0 × 10(-6) cells, respectively. CONCLUSIONS: The authors report the occurrence of ETV6-NTRK3 rearrangements in thyroid cancer and demonstrate that this rearrangement is significantly more common in tumors associated with exposure to (131) I and has a borderline significant dose response. Moreover, ETV6-NTRK3 rearrangement can be directly induced in thyroid cells by ionizing radiation in vitro and, thus, may represent a novel mechanism of radiation-induced carcinogenesis.

Country of origin, age at migration and risk of cutaneous melanoma: a migrant cohort study of 1,100,000 Israeli men.

Cutaneous melanoma (CM) is a common cancer with increasing incidence in many parts of the world where light-skinned populations live. We conducted a large-scale nationally representative migrant cohort study to assess country of origin and age at migration as predictors of CM, controlling for possible confounders. Data on 1,086,569 Israeli Jewish males, who underwent a general health examination before compulsory military service at ages 16-19 between the years 1967-2005, were linked to Israel National Cancer Registry to obtain incident CM up to 2006. Cox proportional hazards was used to model time to event. Overall, 1562 incident cases were detected during 19.3 million person-years of follow-up. Origin was a strong independent predictor of CM. Incidence was higher for European (hazard ratio [HR] = 4.08, 95% confidence interval [CI]: 3.55-4.67) and Israeli origin (HR = 2.92, 95% CI: 2.25-3.79) compared to N. African/Asian origin, adjusted for year of birth, years of education, residential socio-economic position, rural residence and body surface area (or height). Among those of European origin, the adjusted risk was significantly lower for those who immigrated after the age of 10 years (HR = 0.58, 95% CI: 0.45-0.73) but not for younger ages (HR = 1.02, 95% CI 0.84-1.23) compared to Israeli born. The high rates of CM among men of European origin and the almost twofold lower risk among those immigrating after age 10 provide solid support for the deleterious role of childhood sun exposure as a risk factor for melanoma. These findings will serve in directing public health and research efforts.

[Skin cancer risk factors in childhood: findings of a survey conducted within Italian areas with a different incidence of melanoma]. / Infanzia e fattori di rischio per tumori della cute: risultati di un indagine in aree italiane a diversa incidenza di melanoma cutaneo.

OBJECTIVE: to evaluate the association between phenotype and sun sensitivity factors, sun protection behavior, ethnicity and the area of residence in school-aged children. DESIGN: a cross-sectional study in the framework of a survey of children using a self-administered questionnaire to be filled in by parents. SETTING AND PARTICIPANTS: 56390 children attending primary schools located in the Italian provinces of Brindisi, Rome, Forlì and Genova, in the period between 1998-2002. MAIN OUTCOME MEASURES: Odds Ratios (ORs) and their relative 95% Confidence Intervals (95% CI) are to be computed through univariate and multivariate logistic regression models. RESULTS: "FOTO positive" phenotype, a proxy variable of the fair phenotype, was directly and significantly associated with the tendency to sunburn (OR 4.75; 95% CI 4.54-4.96), the use of sunscreens (OR 1.79; 95% CI 1.63-1.97), the number of grandparents born in the northern areas (OR 1.63; 95% CI 1.45-1.83, for four northern grandparents versus none), the presence of freckles on the face (OR 1.62; 95% CI 1.53-1.72) and of naevi on the left forearm (OR 1.20; 95% CI 1.15-1.26). A positive association was also found for the residence in the northern areas using the area of Brindisi as the reference category, (Rome: OR 1.02; 95% CI 0.95-1.10; Forlì: OR 1.05; 95% CI 0.96-1.15; Genova: OR 1.16; 95% CI 1.08-1.26); the ORs increase with latitude, as does the incidence rate of melanoma in Italy. An inverse association was observed with the male sex (OR 0.92; 95% CI 0.88-0.96), the increase of school-class level (OR 0.65; 95% CI 0.60-0.69, for the highest versus the lowest school-class level) and the ability to tan (OR 0.40; 95% CI 0.36-0.43). CONCLUSION: these findings confirmed that the fairness phenotype is associated with other skin cancer risk factors in children and pointed out that the high-risk phenotype has a geographical distribution consistent with the pattern of melanoma incidence in the Italian areas covered by the study.

Radiation doses from global fallout and cancer incidence among reindeer herders and Sami in Northern Finland.

OBJECTIVES: People in the Arctic regions are one of the most heavily exposed population from the global fallout from atmospheric atomic bomb testing of the 1950s and 1960s due to their diet rich in reindeer meat in which radionuclides accumulate. We estimated the effect of the radioactive fallout and ethnicity on the cancer incidence in Northern Finland. METHODS: A cohort of the Arctic population in Finland (n=34,653) was identified through the Population Register Centre with grouping by reindeer herding status, ethnicity and radiation exposure. Annual average radiation doses, based on (137)Cs whole-body measurements, were assigned by birth year, gender and reindeer herder status. Incident cancer cases of a priori selected cancer types in the study cohort during 1971-2005 were identified from the Finnish Cancer Registry. RESULTS: A total of 2630 cancer cases were observed versus 3073 expected on the basis of incidence rates in Northern Finland (standardised incidence ratio (SIR) was 0.86 with 95% CI of 0.82 to 0.89). For the indigenous Sami people SIR was even lower, 0.60 (95% CI 0.50 to 0.71). None of the cancer sites was significantly associated with the lifetime cumulative radiation dose. The SIR for the combined group of radiation-related cancer sites increased with the cumulative radiation dose received before 15 years of age (p=0.004). CONCLUSION: Despite the low overall cancer incidence in the Arctic population and ethnic Sami people in Finland and lack of association between the lifetime cumulative radiation exposure from global radioactive fallout and cancer incidence, we found some indication of an increased cancer risk associated with radiation exposure received during childhood. Potential underestimation and misclassification of the radiation dose may affect the results and the findings should be interpreted with caution.

Health disparities among different ethnic and racial middle and high school students in sun exposure beliefs and knowledge.

Racial and ethnic differences may influence sun protection behavior. Adolescent students were administered a sun protection questionnaire and educational program. White people had the greatest pretest knowledge which resulted in the highest score, and blacks and Hispanics scored lower. White people who found tanned individuals attractive had greater score improvements. All groups improved after intervention.

Public health, racial tensions, and body politic: mass ringworm irradiation in Israel, 1949-1960.

In this essay, we analyze the case study of mass ringworm irradiation conducted in Israel during its first years of existence and its consequences. We analyzed the case study of ringworm irradiation in the framework of racial construction of illness and its treatment, showing the elasticity of race and ethnicity as medical and social categories.

Sun exposure and non-Hodgkin lymphoma.

It was initially hypothesized that sun exposure might cause non-Hodgkin lymphoma (NHL) on the following grounds: its incidence was increasing in parallel with that of cutaneous melanoma; its risk was increased in those with a history of melanoma or other skin cancer; sun exposure causes immune suppression; and immunosuppression for other reasons is associated with an increased risk of NHL. The association of NHL with prior skin cancer has been found consistently in subsequent studies, but results of ecological analyses have only partially supported this hypothesis. Contrary to it, three recent studies of NHL in individuals found that risk decreased, generally by 25% to 40%, across categories of increasing total or recreational, but not occupational, sun exposure. One study, thus far reported only in abstract, showed the opposite. Production of vitamin D from sun exposure offers a plausible mechanism for protection against NHL by sun exposure. A recent study has found a reduced risk of NHL in people with a high dietary intake of vitamin D. Results of additional studies in individuals and a planned original-data meta-analysis of case-control studies should help to resolve the present conflicting results on sun exposure and NHL.

Risk of thyroid cancer after childhood exposure to ionizing radiation for tinea capitis.

BACKGROUND: The thyroid gland is known to be sensitive to the carcinogenic effect of ionizing radiation, especially in children. The role of potential modifiers of the risk and latency period effects needs further investigation. We examined the effect of low doses of ionizing radiation (4.5-49.5 cGy) on the risk of developing thyroid cancer after long latent periods of up to 54 yr after childhood exposure. METHODS: The study population included 10,834 individuals irradiated against tinea capitis in the 1950s and two matched nonirradiated groups (general population and siblings) for comparison. Cancer statistics and vital status data were obtained from national registries, updated to December 2002. Excess relative and absolute risks [excess relative risk per gray (ERR/Gy), excess absolute risk (EAR)] were estimated using Poisson regression for survival analysis. RESULTS: Within the study period, 159 cases of thyroid cancer were diagnosed. Total ERR/Gy and excess absolute risk per gray per 10(4) person-years for developing thyroid cancer reached 20.2 (95% confidence interval 11.8-32.3) and 9.9 (95% confidence interval 5.7-14.7), respectively. The risk was positively associated with dose and negatively associated with age at exposure. ERR/Gy was significantly elevated 10-19 yr after exposure, peaking at 20-30 yr, and decreasing dramatically (although still significantly elevated) 40 yr after exposure. CONCLUSIONS: Our findings agree with patterns of risk modification seen in most studies of radiation-induced thyroid cancer, although risk per unit dose seems higher. Our data show that 40 yr after irradiation, ERR decreases dramatically, although remaining significantly elevated. The hypothesis of different genetic susceptibility of the Jewish population deserves further exploration.

Childhood cancer among Alaska Natives.

OBJECTIVE: The primary purpose of this study was to examine the occurrence of cancer in Alaska Native (AN) children (under age 20). Although several studies have compared differences in cancer incidence between white and black children, few have examined cancer among Alaska Natives/American Indians. We know of no published article describing cancer incidence in AN children. We compared our findings with those of American Indian children of New Mexico and of Alaska white children. Data on mortality, survival, and prevalence are also included. Alaska Native is the term used collectively for the inhabitants whose ancestors occupied the area before European contact of what is now the state of Alaska. Alaska Natives include Eskimo, Indian, and Aleut groups. Although the 3 major groups differ in culture, language, and probably genetics, there are similarities in numerous social and economic indicators. The Northern Eskimo of Alaska (Inupiat) are related to Canadian and Greenland Inuit. Indians in Alaska include Athabaskan (in the interior of the state), who share commonalities with Canadian Athabaskan as well as with Navajo and Apache in the southwestern United States. Tlingit, Haida, and Tsimshian groups reside primarily in the southeast panhandle of the state. The panhandle Indian groups are similar to those of British Columbia. METHODS: Data on cancer incidence are from the Alaska Native Tumor Registry, 1969-1996. We studied children under age 20 to make our results comparable to national data as presented in the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) Pediatric Monograph. Population data for AN are based on census data and Indian Health Service intercensal estimates. Data for US whites and New Mexico Indians are from the National Cancer Institute's SEER program. Calculations were made using SEERStat software. Data for Alaska whites are for the years 1996-2000. (The Alaska Cancer Registry has collected data for all Alaskans only since 1996). Odds ratios (ORs) of rates with 95% confidence intervals (CIs) were calculated. RESULTS: The rate among all AN children (both sexes) for all cancers combined is similar to that of US whites (OR: 1.0; 95% CI: 0.8-1.1). Examination of childhood cancer rates by ethnicity, however, reveal that rates are significantly lower for Indian (OR: 0.6; 95% CI: 0.4-0.8) but not significantly different for Eskimo or Aleut children. For most International Classification of Childhood Cancers groups, incidence rates for AN children are also similar to those of US whites. However, AN children are at significantly higher risk for hepatic tumors (OR: 13.1; 95% CI: 7.9-20.5), particularly hepatocellular carcinoma (OR: 43.8; 95% CI:24.4-75.1) and retinoblastoma (OR: 2.8; 95% CI: 1.3-5.3). By ethnic group, rates for hepatocellular carcinoma are significantly high only for Eskimo. Rates for all AN children are lower for neuroblastoma (OR: 0.1; 95% CI: 0.1-0.6) and lymphoma (OR: 0.5; 95% CI: 0.3-0.9), particularly Hodgkin's disease (OR: 0.2; 95% CI: 0.0-0.5). On the basis of 5 years of data, rates for Alaska white children do not seem to differ from those of US white children. Because of our findings of differences between AN and US whites, we reviewed data of other relevant populations, specifically American Indian data from the New Mexico SEER registry. Using SEER data and SEER software, we calculated rates for New Mexican American Indians (NMAI) and compared them with US white rates. Rates for all cancers combined among NMAI are significantly lower than for US white (OR: 0.8). However, similar to AN children, the rate among NMAI for retinoblastoma is higher compared with US whites (OR: 2.5; 95% CI:1.4-4.5). Similar to AN, NMAI also seem to be at low risk for neuroblastoma (OR: 0.2; 95% CI: 0.1-0.7), lymphoma as a group (OR: 0.1; 95% CI: 0.0-0.3), and, specifically, Hodgkin's disease (OR: 0.1; 95% CI: 0.0-0.4). Rates among NMAI children are low for central nervous system tumors (OR: 0.5; 95% CI: 0.3-0.7). The average annual age-adjusted cancer mortality rate among AN children is lower but not significantly lower than that of US white children (28.6 vs 37.3 per million). CONCLUSIONS: Comparison of AN rates for all cancers combined are similar to those of US and Alaska white children but seem higher than those of NMAI. Differences between AN and US whites exist for select International Classification of Childhood Cancers groups. The most striking rate differences are found in hepatic tumors, largely because of elevated rates of hepatitis B-associated hepatocellular carcinoma. All children in our study with hepatocellular carcinoma were hepatitis B antigen positive. A statewide hepatitis B virus immunization program was begun in late 1982. Although 16 children who were born before 1983 developed hepatocellular carcinoma, no children who were born in the 20 years since hepatitis B immunization was instituted among infants have received a diagnosis of hepatocellular carcinoma, a significant difference. Comparing AN and US white childhood cancer rates after removing hepatocellular carcinoma cases from both populations results in an OR of 0.8 (95% CI: 0.7-1.0). Thus, if no increase in other childhood cancers occurs in the coming generations, then rates for childhood cancer may soon be significantly lower than those in US white children. Rates are low for all lymphomas, largely because of very low rates of Hodgkin's disease. Rates are also low for neuroblastoma. It is reassuring that rates for AN children are not in excess and do not seem to be increasing. There is concern among the population regarding environmental exposure, including ionizing radiation. Our data do not show excess childhood leukemia or thyroid cancers, malignancies for which radiation is known to increase risk.

The history of uranium mining and the Navajo people.

From World War II until 1971, the government was the sole purchaser of uranium ore in the United States. Uranium mining occurred mostly in the southwestern United States and drew many Native Americans and others into work in the mines and mills. Despite a long and well-developed understanding, based on the European experience earlier in the century, that uranium mining led to high rates of lung cancer, few protections were provided for US miners before 1962 and their adoption after that time was slow and incomplete. The resulting high rates of illness among miners led in 1990 to passage of the Radiation Exposure Compensation Act.

Risk factors for basal cell carcinoma in a Mediterranean population: role of recreational sun exposure early in life.

OBJECTIVE: To investigate the role of pigmentary traits, different patterns of sun exposure, artificial sources of UV radiation, and lifestyle-related factors on the risk of basal cell carcinoma (BCC) in a Mediterranean population from central-southern Italy. DESIGN: Hospital-based case-control study. SETTING: A referral dermatological hospital in Rome, Italy. PATIENTS: A convenience sample of 166 case patients with histologically confirmed BCC and 158 cancer-free control subjects with minor dermatological conditions observed between March 1995 and June 1997. RESULTS: In the multivariate analysis, the mean number of weeks per year spent at the beach before the age of 20 years was significantly associated with BCC. A dose-response trend was found for subjects who had spent 3 to 4 (odds ratio, 1.8; 95% confidence interval, 0.8-4.4), 5 to 8 (odds ratio, 3.7; 95% confidence interval, 1.5-9.0), or more than 8 (odds ratio, 4.5; 95% confidence interval, 1.9-10.5) weeks per year at the beach (P =.01 for trend). There was a significant association with the presence of actinic keratoses or solar lentigines, whereas no effect was found for skin type, history of sunburns, exposure to nonsolar UV radiation, and lifestyle-related habits such as cigarette smoking, alcohol consumption, and coffee drinking. Subjects reporting a family history of skin cancer had an extremely increased risk of BCC. CONCLUSION: The definite association with recreational sun exposure during childhood and adolescence and the strong relation with family history of skin cancer suggest that genetic predisposition and peculiar exposure patterns to UV radiation are key independent risk factors for the development of BCC in a southern European population.