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Amy Berrington de Gonzalez,
Patricia Hartge,
James R Cerhan,
Alan J Flint,
Lindsay Hannan,
Robert J MacInnis,
Steven C Moore,
Geoffrey S Tobias,
Hoda Anton-Culver,
Laura Beane Freeman, [......],
Yikyung Park,
Gaia Pocobelli,
Arthur Schatzkin,
Howard D Sesso,
Elisabete Weiderpass,
Bradley J Willcox,
Alicja Wolk,
Anne Zeleniuch-Jacquotte,
Walter C Willett,
Michael J Thun
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Timothy J Jorgensen,
Ingo Ruczinski,
Yin Yao Shugart,
Lee Wheless,
Yvette Berthier Schaad,
Bailey Kessing, Judith Hoffman-Bolton,
Kathy J Helzlsouer,
W H Linda Kao,
Lesley Francis,
Rhoda M Alani,
Paul T Strickland,
Michael W Smith,
Anthony J Alberg
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ABSTRACT: Introduction: A personal history of basal cell carcinoma (BCC) is associated with increased risk of other malignancies, but the reason is unknown. The hedgehog pathway is critical to the etiology of BCC, and is also believed to contribute to susceptibility to other cancers. This study tested the hypothesis that hedgehog pathway and pathway-related gene variants contribute to the increased risk of subsequent cancers among those with a history of BCC. Methods: The study was nested within the ongoing CLUE II cohort study, established in 1989 in Washington County, Maryland, USA. The study consisted of a cancer-free control group (n=2296) compared to three different groups of cancer cases ascertained through 2007, those diagnosed with: (1) Other (non-BCC) cancer only (n=2349); (2) BCC only (n=534); and (3) BCC plus other cancer (n=446). The frequencies of variant alleles were compared among these four groups for 20 single nucleotide polymorphisms (SNPs) in 6 hedgehog pathway genes (SHH, IHH, PTCH2, SMO, GLI1, SUFU), and also 22 SNPs in VDR and 8 SNPs in FAS, which have cross-talk with the hedgehog pathway. Results: Comparing those with both BCC and other cancer versus those with no cancer, no significant associations were observed for any of the hedgehog pathway SNPs, or for the FAS SNPs. One VDR SNP was nominally significantly associated with the BCC cancer-prone phenotype, rs11574085 [per minor allele odds ratio (OR) 1.38, 95% confidence interval (CI) 1.05-1.82; p-value=0.02]. Conclusion: The hedgehog pathway gene SNPs studied, along with the VDR and FAS SNPs studied, are not strongly associated with the BCC cancer-prone phenotype.
Cancer epidemiology. 06/2012; 36(5):e288-93.
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Lee Wheless,
Emily Kistner-Griffin,
Timothy J Jorgensen,
Ingo Ruczinski,
Yvette Berthier-Schaad,
Bailey Kessing, Judith Hoffman-Bolton,
Lesley Francis,
Yin Yao Shugart,
Paul T Strickland,
W H Linda Kao,
Rhoda M Alani,
Michael W Smith,
Anthony J Alberg
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ABSTRACT: Nucleotide excision repair (NER) is responsible for protecting DNA in skin cells against UVR-induced damage. Using a candidate pathway approach, a matched case-control study nested within a prospective, community-based cohort was carried out to test the hypothesis that single-nucleotide polymorphisms (SNPs) in NER genes are associated with susceptibility to non-melanoma skin cancer (NMSC). Histologically confirmed cases of NMSC (n=900) were matched to controls (n=900) on the basis of age, gender, and skin type. Associations were measured between NMSC and 221 SNPs in 26 NER genes. Using the additive model, two tightly linked functional SNPs in ERCC6 were significantly associated with increased risk of NMSC: rs2228527 (odds ratio (OR) 1.57, 95% confidence interval (CI) 1.20-2.05) and rs2228529 (OR 1.57, 95% CI 1.20-2.05). These associations were confined to basal cell carcinoma (BCC) of the skin (rs2228529, OR 1.78, 95% CI 1.30-2.44; rs2228527, OR 1.78, 95% CI 1.31-2.43). These hypothesis-generating findings suggest that functional variants in ERCC6 may be associated with an increased risk of NMSC that may be specific to BCC.
Journal of Investigative Dermatology 02/2012; 132(5):1354-62. · 6.31 Impact Factor
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Amy Berrington de Gonzalez,
Patricia Hartge,
James R Cerhan,
Alan J Flint,
Lindsay Hannan,
Robert J MacInnis,
Steven C Moore,
Geoffrey S Tobias,
Hoda Anton-Culver,
Laura Beane Freeman, [......],
Yikyung Park,
Gaia Pocobelli,
Arthur Schatzkin,
Howard D Sesso,
Elisabete Weiderpass,
Bradley J Willcox,
Alicja Wolk,
Anne Zeleniuch-Jacquotte,
Walter C Willett,
Michael J Thun
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ABSTRACT: A high body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) is associated with increased mortality from cardiovascular disease and certain cancers, but the precise relationship between BMI and all-cause mortality remains uncertain.
We used Cox regression to estimate hazard ratios and 95% confidence intervals for an association between BMI and all-cause mortality, adjusting for age, study, physical activity, alcohol consumption, education, and marital status in pooled data from 19 prospective studies encompassing 1.46 million white adults, 19 to 84 years of age (median, 58).
The median baseline BMI was 26.2. During a median follow-up period of 10 years (range, 5 to 28), 160,087 deaths were identified. Among healthy participants who never smoked, there was a J-shaped relationship between BMI and all-cause mortality. With a BMI of 22.5 to 24.9 as the reference category, hazard ratios among women were 1.47 (95 percent confidence interval [CI], 1.33 to 1.62) for a BMI of 15.0 to 18.4; 1.14 (95% CI, 1.07 to 1.22) for a BMI of 18.5 to 19.9; 1.00 (95% CI, 0.96 to 1.04) for a BMI of 20.0 to 22.4; 1.13 (95% CI, 1.09 to 1.17) for a BMI of 25.0 to 29.9; 1.44 (95% CI, 1.38 to 1.50) for a BMI of 30.0 to 34.9; 1.88 (95% CI, 1.77 to 2.00) for a BMI of 35.0 to 39.9; and 2.51 (95% CI, 2.30 to 2.73) for a BMI of 40.0 to 49.9. In general, the hazard ratios for the men were similar. Hazard ratios for a BMI below 20.0 were attenuated with longer-term follow-up.
In white adults, overweight and obesity (and possibly underweight) are associated with increased all-cause mortality. All-cause mortality is generally lowest with a BMI of 20.0 to 24.9.
New England Journal of Medicine 12/2010; 363(23):2211-9. · 53.30 Impact Factor
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Mark P Purdue,
D Michal Freedman,
Susan M Gapstur,
Kathy J Helzlsouer,
Francine Laden,
Unhee Lim,
Gertraud Maskarinec,
Nathaniel Rothman,
Xiao-Ou Shu,
Victoria L Stevens, [......], Judith Hoffman-Bolton,
Edward L Giovannucci,
Laurence N Kolonel,
Kirk Snyder,
Walter Willett,
Alan A Arslan,
Richard B Hayes,
Wei Zheng,
Yong-Bing Xiang,
Patricia Hartge
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ABSTRACT: Case-control studies generally suggesting an inverse association between sun exposure and non-Hodgkin lymphoma (NHL) have led to speculation that vitamin D may protect against lymphomagenesis. To examine this hypothesis, the authors conducted a pooled investigation of circulating 25-hydroxyvitamin D (25(OH)D) and subsequent NHL risk within 10 cohorts participating in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. The authors analyzed measurements from 1,353 cases and 1,778 controls using conditional logistic regression and other methods to estimate the association of 25(OH)D with NHL. No clear evidence of association between categories of 25(OH)D concentration and NHL was observed overall (P(trend) = 0.68) or by sex (men, P(trend) = 0.50; women, P(trend) = 0.16). Findings for other measures (continuous log(25(OH)D), categories of 25(OH)D using sex-/cohort-/season-specific quartiles as cutpoints, categories of season-adjusted residuals of predicted 25(OH)D using quartiles as cutpoints) were generally null, although some measures of increasing 25(OH)D were suggestive of an increased risk for women. Results from stratified analyses and investigations of histologic subtypes of NHL were also null. These findings do not support the hypothesis that elevated circulating 25(OH)D concentration is associated with a reduced risk of NHL. Future research investigating the biologic basis for the sunlight-NHL association should consider alternative mechanisms, such as immunologic effects.
American journal of epidemiology 07/2010; 172(1):58-69. · 5.59 Impact Factor
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ABSTRACT: Several previous studies have reported inverse associations between cigarette smoking and melanoma. Often these studies have not adjusted for ultraviolet (UV) exposure history, skin type, or number of blistering sunburns, which could confound the observed associations between cigarette smoking and melanoma.
We sought to assess whether this reported inverse association persists after adjusting for UV exposure, skin type, and number of blistering sunburns.
We conducted a population-based case-control study (82 patients with melanoma, 164 control subjects). Two control subjects were matched to each patient by age, sex, race, and skin type. Conditional logistic regression models were fit to assess the association between cigarette smoking history and melanoma, with additional adjustments for UV exposure and sunburns.
Compared with never smoking, both former (odds ratio 0.43, 95% confidence interval 0.18-1.04) and current (odds ratio 0.65, 95% confidence interval 0.19-2.24) smoking were inversely associated with melanoma, but the associations were not statistically significant.
The number of cutaneous nevi was not assessed in this study. In addition, the relatively small number of patients limits the statistical precision of the observed associations.
After matching for age, sex, race, and skin type, and further adjusting for UV exposure and number of sunburns, cigarette smoking was not statistically significantly associated with melanoma risk, but the results were consistent with previous observations of an inverse association.
Journal of the American Academy of Dermatology 03/2010; 64(1):84-90. · 3.99 Impact Factor
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ABSTRACT: Metabolic syndrome components have been associated with colorectal cancer in several studies; however, evidence for colorectal adenomas is limited. Thus, we evaluated the association between markers of the metabolic syndrome with colorectal adenoma development in a nested case-control study.
Colorectal adenoma cases (n = 132) and matched controls, who had a negative sigmoidoscopy or a colonoscopy (n = 260), were identified between baseline in 1989 and 2000 among participants in the CLUE II cohort of Washington County, Maryland. Concentrations of C-peptide, insulin-like growth factor binding protein-1, glycosylated hemoglobin, total cholesterol, high-density lipoprotein cholesterol, and triglycerides were measured in baseline blood specimens. Body mass index was calculated using baseline height and weight. Use of medications to treat diabetes mellitus was self-reported at baseline. Blood pressure was measured at baseline. Distributional cutpoints of the latter markers were used to define the metabolic syndrome components (hyperinsulinemia, hyperglycemia, obesity, dyslipidemia, and hypertension) present at baseline.
No statistically significant associations with adenomas were observed for the markers of the metabolic syndrome, with the exception of a strong positive association for use of diabetes medications (OR, 8.00; 95% CI, 1.70-37.67), albeit based on small numbers.
Our findings do not support that components of the metabolic syndrome influence risk of colorectal adenomas, except possibly for severe diabetes mellitus warranting medical treatment.
Cancer Causes and Control 09/2009; 21(1):1-10. · 2.88 Impact Factor
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ABSTRACT: Behaviors such as sunscreen use and wearing sun-protective clothing are thought to prevent certain types of skin cancer and precancerous lesions, but few studies have examined differences in these prevention behaviors by skin type.
We carried out a cross-sectional study (n = 6,858) nested within a community-based prospective cohort in Washington County, Maryland. We measured the associations between skin type, complexion, freckling, and eye color, and sunscreen and sun-protective clothing use.
The prevalence of regular sunscreen use was 23% and regular sun-protective clothing use was 21%. There were consistent trends indicating those with the most sun-sensitive skin type were most likely to engage in prevention behaviors. For example, compared with those who tan without burning, those who develop blistering sunburns were more likely to use sunscreen [odds ratio (OR), 6.04; 95% confidence interval (95% CI), 2.82-12.95 men; OR, 4.89; 95% CI, 3.34-7.16 women] and sun-protective clothing (OR, 2.87; 95% CI, 1.71-4.80 men; OR, 4.44; 95% CI, 2.88-6.85 women). Health-related characteristics such as body mass index and cigarette smoking were also significantly inversely associated with prevention behaviors.
The overall prevalence of prevention behaviors was low. Those with phenotypic risk factors for skin cancer were most likely to use sunscreen and sun-protective clothing. Those with high-risk skin cancer phenotypes may also be those who are most receptive to skin cancer prevention educational interventions.
Cancer Epidemiology Biomarkers & Prevention 09/2009; 18(10):2613-9. · 4.12 Impact Factor
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ABSTRACT: The association of 17 candidate single nucleotide polymorphisms (SNPs) in IL10 and other immune response genes (CRP, TLR4, IL6, IL1B, IL8, TNF, RNASEL) and genes related to obesity (PPARG, TCF7L2, ADIPOQ, LEP) with colorectal cancer was investigated. Haplotype tagging SNPs were chosen for IL10, CRP, and TLR4. Incident colorectal cancer cases (n = 208) and matched controls (n = 381) were identified between baseline in 1989 and 2003 among participants in the CLUE II cohort. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using conditional logistic regression.
Compared with the AA genotype at the candidate IL10-1082 locus (rs1800896), carrying one (OR, 0.79; 95% CI, 0.53-1.18) or two (OR, 0.58; 95% CI, 0.35-0.95) G alleles, a known higher producer of the anti-inflammatory cytokine IL-10, was associated with lower risk of colorectal cancer (p trend = 0.03). Statistically significant associations with colorectal cancer were observed for three tagSNPs in IL10 (rs1800890, rs3024496, rs3024498) and one common haplotype, but these associations were due to high linkage disequilibrium with IL10-1082. Two CRP haplotypes (global p = 0.04) and TLR4 tagSNPs (rs7873784, rs11536891), but not TLR4 haplotypes, were associated with colorectal cancer.
Our study suggests that polymorphisms in IL10, and also possibly in CRP and other genes related to immune response or obesity may be associated with colorectal cancer.
Cancer Causes and Control 09/2009; 20(9):1739-51. · 2.88 Impact Factor
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Jiping Chen,
Ingo Ruczinski,
Timothy J Jorgensen,
Gayane Yenokyan,
Yin Yao,
Rhoda Alani,
Nanette J Liégeois,
Sandra C Hoffman, Judith Hoffman-Bolton,
Paul T Strickland,
Kathy J Helzlsouer,
Anthony J Alberg
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ABSTRACT: Individuals with a personal history of nonmelanoma skin cancer (NMSC) may have an increased risk of subsequent noncutaneous malignancies. To test this hypothesis, we carried out a community-based, prospective cohort study.
In the CLUE (Give Us a Clue to Cancer and Heart Disease) II cohort, which was established in Washington County, MD, in 1989, the risk of new malignancies was compared among individuals with (n = 769) and without (n = 18,405) a personal history of NMSC (total n = 19,174) during a 16-year follow-up period. Pathologically confirmed NMSC (and other malignancies) were ascertained from the Washington County Cancer Registry. Cox regression analysis with time-dependent covariates was used to determine the hazard ratios (presented as multivariable-adjusted relative risks [RRs]) and 95% confidence intervals (CIs) of second primary malignancies associated with a previously confirmed NMSC diagnosis. All statistical tests were two-sided.
The crude incidence rate (per 10,000 person-years) of subsequent cancers other than NMSC among participants with a positive personal history of NMSC was 293.5 and with a negative history was 77.8. Compared with persons with no personal history of NMSC, those with such a history had a statistically significantly increased risk of being diagnosed with a subsequent cancer other than NMSC (RR = 1.99, 95% CI = 1.70 to 2.33) after adjusting for age, sex, body mass index, smoking status, and educational level. The association was observed for both basal cell carcinoma (multivariable-adjusted RR = 2.03, 95% CI = 1.70 to 2.42) and squamous cell carcinoma (multivariable-adjusted RR = 1.97, 95% CI = 1.50 to 2.59) of the skin. NMSC was a statistically significantly stronger cancer risk factor in younger age groups than in older age groups (P for interaction = .022).
This community-based, prospective cohort study provides evidence for an association between an NMSC diagnosis and an increased risk of subsequent cancer, even after adjusting for individual-level risk factors.
CancerSpectrum Knowledge Environment 10/2008; 100(17):1215-22. · 14.07 Impact Factor
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ABSTRACT: The public has long been encouraged to engage in sun-safe practices to minimize exposure to sunlight, the major cause of nonmelanoma skin cancer. More recently, some have advocated unprotected sun exposure to increase cutaneous synthesis of vitamin D as a way to promote health. We assessed the net result of these conflicting messages.
In a cross-sectional survey in 2007, questionnaires were mailed to participants of an ongoing cohort study in Washington County, Maryland. The study population consisted of 8,027 adults (55% response rate).
Thirty percent of respondents were aware that unprotected sun exposure increased endogenous vitamin D levels. Among those who were aware of this benefit, 42% reported going out into the sun to increase vitamin D levels. Sun-seeking to increase vitamin D production did not significantly differ according to self-reported personal history of skin cancer, but was significantly higher among women, older age groups, those with less education, and vitamin D supplement users.
A substantial proportion of respondents reported sun-seeking behavior expressly to increase endogenous vitamin D levels. The message about sun exposure and vitamin D is reaching the general public; however, this finding poses challenges to skin cancer prevention efforts.
Public Health Reports 126(4):533-9. · 1.27 Impact Factor
