Showing papers by "Margaret R. Karagas published in 2002"

Use of Tanning Devices and Risk of Basal Cell and Squamous Cell Skin Cancers

Abstract: Use of artificial tanning devices that emit UV radiation, such as tanning lamps and tanning beds, has become increasingly popular in the United States. Although an excess risk of nonmelanoma skin cancers might be predicted from this exposure, little epidemiologic data exist. We conducted a population-based, case-control study that included 603 basal cell carcinoma (BCC) case patients, 293 squamous cell carcinoma (SCC) case patients, and 540 control subjects. Study participants were interviewed in person to obtain information on tanning device use, sun exposure history, sun sensitivity, and other risk factors for skin cancer. Overall, any use of tanning devices was associated with odds ratios of 2.5 (95% confidence interval [CI] = 1.7 to 3.8) for SCC and 1.5 (95% CI = 1.1 to 2.1) for BCC. Adjustment for history of sunburns, sunbathing, and sun exposure did not affect our results. Our findings suggest that the use of tanning devices may contribute to the incidence of nonmelanoma skin cancers. They highlight the need to further evaluate the potential risks of BCC and SCC that are associated with tanning lamp exposure and the appropriate public health response.

The XRCC1 Arg399Gln polymorphism, sunburn, and non-melanoma skin cancer: evidence of gene-environment interaction.

Abstract: XRCC1, a protein directly involved in the repair of DNA base damage, contains at least three common polymorphisms. One of these, the codon 399 arg→gln variant, has been associated with several cancer-related biomarkers, suggesting it may have functional significance in exposure-induced cancers. However, results from case-control studies have yielded conflicting results. We investigated the XRCC1 arg399gln polymorphism and its interaction with carcinogen exposure in a large, population-based case-control study of non-melanoma skin cancer. Cases were derived from an incident survey of all newly diagnosed non-melanoma skin cancer in New Hampshire, and controls were population based and frequency matched to cases on age and sex ( n = 1176). Exposure information was derived from a detailed interviewer-administered questionnaire, and XRCC1 genotype was determined from blood-derived DNA using a PCR-RFLP method. Overall, the XRCC1 homozygous variant gln399gln genotype was related to a significantly reduced risk of both basal cell [BCC; odds ratio (OR) 0.7, 95% confidence interval 0.4–1.0] and squamous cell carcinoma (SCC; OR 0.6, 95% confidence interval 0.3–0.9). There was no significant gene-environment interaction of the variant XRCC1 genotype and a history of therapeutic X-ray exposure. However, there was a statistically significant multiplicative interaction of XRCC1 genotype and lifetime number of sunburns in SCC [likelihood ratio test (2 d.f.), P XRCC1 variant (gln399gln) is associated with a lower risk of non-melanoma skin cancer and suggest that the etiology of sunburn-related SCC may be significantly different by XRCC1 genotype. These data, using the classic skin carcinogenesis model, provide new insight on the role of the XRCC1 399 polymorphism in neoplasia and may help explain the conflicting results relating this polymorphism to cancer risk at various sites.

A pooled analysis of 10 case-control studies of melanoma and oral contraceptive use.

Abstract: Data regarding the effects of oral contraceptive use on women's risk of melanoma have been difficult to resolve. We undertook a pooled analysis of all case–control studies of melanoma in women completed as of July 1994 for which electronic data were available on oral contraceptive use along with other melanoma risk factors such as hair colour, sun sensitivity, family history of melanoma and sun exposure. Using the original data from each investigation (a total of 2391 cases and 3199 controls), we combined the study-specific odds ratios and standard errors to obtain a pooled estimate that incorporates inter-study heterogeneity. Overall, we observed no excess risk associated with oral contraceptive use for 1 year or longer compared to never use or use for less than 1 year (pooled odds ratio (pOR)=0.86; 95% CI=0.74–1.01), and there was no evidence of heterogeneity between studies. We found no relation between melanoma incidence and duration of oral contraceptive use, age began, year of use, years since first use or last use, or specifically current oral contraceptive use. In aggregate, our findings do not suggest a major role of oral contraceptive use on women's risk of melanoma. British Journal of Cancer (2002) 86, 1085–1092. DOI: 10.1038/sj/bjc/6600196 www.bjcancer.com © 2002 Cancer Research UK

Microsatellite instability at tetranucleotide repeats in skin and bladder cancer.

Abstract: Recently, a novel form of MSI has been described that occurs only at tetranucleotide repeat markers. This has been termed elevated microsatellite instability at selected tetranucleotide repeats (EMAST). EMAST has been related to alterations of the p53 gene, and to the nature of the repeat sequence. We initially tested whether loss of heterozygosity (LOH) at the p53 and the patched (ptch) genes was related to EMAST in a series of 61 non-melanoma skin cancer (NMSC) tumors. We then analysed a series of 57 primary bladder cancers for the presence of EMAST, testing whether this was related to mutation or expression of the p53 gene. In both NMSC and bladder tumors we found a high prevalence of EMAST (75.4 and 43.9%). In NMSC the prevalence of EMAST was higher in tumors that had either p53 or ptch LOH, although the difference was not statistically significant. There was a significant association of extensive EMAST (three or more loci) with mutations in p53 among the bladder cancer tumors, but no indication of elevated EMAST in tumors with abnormal p53 staining without mutation. The association of EMAST with p53 mutation was confined to non-invasive disease. Hence, EMAST likely reflects a particular pattern of somatic events that are interactive with p53 mutation, particularly common in skin cancer and limited to non-invasive disease in bladder cancer.

Sampling private wells at past homes to estimate arsenic exposure: a methodologic study in New England.

Abstract: We are conducting a collaborative, population-based case-control study in Maine, New Hampshire, and Vermont to investigate the reasons for the elevated bladder cancer mortality in northern New England. Arsenic in drinking water is one of the primary exposures under investigation. To estimate subjects' lifetime exposure to waterborne arsenic, it will be necessary to obtain water samples from private wells that subjects used in the past. We conducted a methodologic study to assess the feasibility of locating and sampling from private wells at subjects' past residences. Ninety-eight New Hampshire residents (mean age 67 years) completed a questionnaire requesting the complete address, dates of occupancy, and drinking water sources for each home lived in since birth. An interviewer then asked subjects for more detailed information about each home to assist in a field search of past homes in the three-state study area of Maine, New Hampshire, and Vermont. Fifty-eight of the 98 subjects indicated that they had used a total of 103 private wells in 95 previous homes located in these three states. We conducted a field search to locate these 95 homes, visited town offices to find the properties on tax maps and obtain the current owners' names and addresses, attempted to obtain permission from the current owners to sample the wells, and collected water samples. In all, 48 (47%) of the 103 past wells in the study area were sampled successfully. The remaining wells were not sampled because the homes were not located (22%) or had been demolished (2%), permission to sample the wells was not obtained (17%), the wells had been destroyed (7%) or could not be found on the grounds of the residence (3%), or for other reasons (2%). Various approaches for improving the success rates for sampling water from private wells are discussed, as is the use of predictive modeling to impute exposures when sampling is not feasible.