Dietary acrylamide and the risk of pancreatic cancer in the International Pancreatic Cancer Case-Control Consortium (PanC4).

Background: Occupational exposure to acrylamide was associated with excess mortality from pancreatic cancer, though in the absence of dose-risk relationship. Few epidemiological studies have examined the association between acrylamide from diet and pancreatic cancer risk. Patients and methods: We considered this issue in a combined set of 1975 cases of pancreatic cancer and 4239 controls enrolled in six studies of the Pancreatic Cancer Case-Control Consortium (PanC4). We calculated pooled odds ratios (ORs) and their 95% confidence intervals (CI) by estimating study-specific ORs through multivariate unconditional logistic regression models and pooling the obtained estimates using random-effects models. Results: Compared with the lowest level of estimated dietary acrylamide intake, the pooled ORs were 0.97 (95% CI, 0.79-1.19) for the second, 0.91 (95% CI, 0.71-1.16) for the third, and 0.92 (95% CI, 0.66-1.28) for the fourth (highest) quartile of intake. For an increase of 10 µg/day of acrylamide intake, the pooled OR was 0.96 (95% CI, 0.87-1.06), with heterogeneity between estimates (I2 = 67%). Results were similar across various subgroups, and were confirmed when using a one-stage modelling approach. Conclusions: This PanC4 pooled-analysis found no association between dietary acrylamide and pancreatic cancer.

Diabetes, antidiabetic medications, and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium.

BACKGROUND: Type 2 diabetes mellitus has been associated with an excess risk of pancreatic cancer, but the magnitude of the risk and the time-risk relationship are unclear, and there is limited information on the role of antidiabetic medications. PATIENTS AND METHODS: We analyzed individual-level data from 15 case-control studies within the Pancreatic Cancer Case-Control Consortium, including 8305 cases and 13 987 controls. Pooled odds ratios (ORs) were estimated from multiple logistic regression models, adjusted for relevant covariates. RESULTS: Overall, 1155 (15%) cases and 1087 (8%) controls reported a diagnosis of diabetes 2 or more years before cancer diagnosis (or interview, for controls), corresponding to an OR of 1.90 (95% confidence interval, CI, 1.72-2.09). Consistent risk estimates were observed across strata of selected covariates, including body mass index and tobacco smoking. Pancreatic cancer risk decreased with duration of diabetes, but a significant excess risk was still evident 20 or more years after diabetes diagnosis (OR 1.30, 95% CI 1.03-1.63). Among diabetics, long duration of oral antidiabetic use was associated with a decreased pancreatic cancer risk (OR 0.31, 95% CI 0.14-0.69, for ≥15 years). Conversely, insulin use was associated with a pancreatic cancer risk in the short term (OR 5.60, 95% CI 3.75-8.35, for <5 years), but not for longer duration of use (OR 0.95, 95% CI 0.53-1.70, for ≥15 years). CONCLUSION: This study provides the most definitive quantification to date of an excess risk of pancreatic cancer among diabetics. It also shows that a 30% excess risk persists for more than two decades after diabetes diagnosis, thus supporting a causal role of diabetes in pancreatic cancer. Oral antidiabetics may decrease the risk of pancreatic cancer, whereas insulin showed an inconsistent duration-risk relationship.

Postmenopausal hormone therapy and non-Hodgkin lymphoma: a pooled analysis of InterLymph case-control studies.

BACKGROUND: Non-Hodgkin lymphoma (NHL) subtypes, diffuse large B-cell (DLBCL) and follicular lymphoma (FL) have different sex ratios and are diagnosed at ages over 60 years; DLBCL is more common in men and diagnosed at older ages than FL, which occurs more among women. This analysis of postmenopausal women examines the relationship between postmenopausal hormone therapy and NHL. DESIGN: Self-reported use of postmenopausal hormone therapy from 2094 postmenopausal women with NHL and 2731 without were pooled across nine case-control studies (1983-2005) from North America, Europe and Japan. Study-specific odds ratios (OR) and 95% confidence intervals (CI) estimated using logistic regression were pooled using random-effects meta-analyses. RESULTS: Postmenopausal women who used hormone therapy were at decreased risk of NHL (pooled OR = 0.79, 95% CI 0.69-0.90). Risks were reduced when the age of starting was 50 years or older. There was no clear trend with number of years of use. Current users were at decreased risk while those stopping over 2 years before diagnosis were not. Having a hysterectomy or not did not affect the risk. Favourable effects were present for DLBCL (pooled OR = 0.66, 95% CI 0.54-0.80) and FL (pooled OR = 0.82, 95% CI 0.66-1.01). CONCLUSION: Postmenopausal hormone therapy, particularly used close to menopause, is associated with a decreased risk of NHL.

Ulcer, gastric surgery and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium (PanC4).

BACKGROUND: Peptic ulcer and its treatments have been associated to pancreatic cancer risk, although the evidence is inconsistent. METHODS: We pooled 10 case-control studies within the Pancreatic Cancer Case-control Consortium (PanC4), including 4717 pancreatic cancer cases and 9374 controls, and estimated summary odds ratios (OR) using multivariable logistic regression models. RESULTS: The OR for pancreatic cancer was 1.10 [95% confidence interval (CI) 0.98-1.23] for history of ulcer (OR = 1.08 for gastric and 0.97 for duodenal ulcer). The association was stronger for a diagnosis within 2 years before cancer diagnosis (OR = 2.43 for peptic, 1.75 for gastric, and 1.98 for duodenal ulcer). The OR was 1.53 (95% CI 1.15-2.03) for history of gastrectomy; however, the excess risk was limited to a gastrectomy within 2 years before cancer diagnosis (OR = 6.18, 95% CI 1.82-20.96), while no significant increased risk was observed for longer time since gastrectomy. No associations were observed for pharmacological treatments for ulcer, such as antacids, H2-receptor antagonists, or proton-pump inhibitors. CONCLUSIONS: This uniquely large collaborative study does not support the hypothesis that peptic ulcer and its treatment materially affect pancreatic cancer risk. The increased risk for short-term history of ulcer and gastrectomy suggests that any such association is due to increased cancer surveillance.

Menstrual and reproductive factors, and hormonal contraception use: associations with non-Hodgkin lymphoma in a pooled analysis of InterLymph case-control studies.

BACKGROUND: The two most common forms of non-Hodgkin lymphoma (NHL) exhibit different sex ratios: diffuse large B-cell lymphoma (DLBCL) occurs more frequently in men and follicular lymphoma (FL) more frequently in women. Looking among women alone, this pooled analysis explores the relationship between reproductive histories and these cancers. MATERIALS AND METHODS: Self-reported reproductive histories from 4263 women with NHL and 5971 women without NHL were pooled across 18 case-control studies (1983-2005) from North America, Europe and Japan. Study-specific odd ratios (ORs) and confidence intervals (CIs) were estimated using logistic regression and pooled using random-effects meta-analyses. RESULTS: Associations with reproductive factors were found for FL rather than NHL overall and DLBCL. In particular, the risk of FL decreased with increasing number of pregnancies (pooled OR(trend) = 0.88, 95% CI 0.81-0.96). FL was associated with hormonal contraception (pooled OR = 1.30, 95% CI 1.04-1.63), and risks were increased when use started after the age of 21, was used for <5 years or stopped for >20 years before diagnosis. DLBCL, on the other hand, was not associated with hormonal contraception (pooled OR = 0.87, 95% CI 0.65-1.16). CONCLUSIONS: Hormonal contraception is associated with an increased risk of FL but not of DLBCL or NHL overall.

Pancreatitis and pancreatic cancer risk: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4).

BACKGROUND: Pancreatitis is a known risk factor for pancreatic cancer; however, an unknown fraction of the disease is thought to be a consequence of tumor-related duct obstruction. PATIENTS AND METHODS: A pooled analysis of a history of pancreatitis and risk of pancreatic cancer was carried out considering the time interval between diagnoses and potential modification by covariates. Adjusted pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from 10 case-control studies (5048 cases of ductal pancreatic adenocarcinoma and 10,947 controls) taking part in the International Pancreatic Cancer Case-Control Consortium (PanC4). RESULTS: The association between pancreatitis and pancreatic cancer was nearly three-fold at intervals of >2 years between diagnoses (OR: 2.71, 95% CI: 1.96-3.74) and much stronger at intervals of ≤2 years (OR: 13.56, 95% CI: 8.72-21.90) probably reflecting a combination of reverse causation and antecedent misdiagnosis of pancreas cancer as pancreatitis. The younger (<65 years) pancreatic cancer cases showed stronger associations with previous (>2 years) pancreatitis (OR: 3.91, 95% CI: 2.53-6.04) than the older (≥65 years) cases (OR: 1.68, 95% CI: 1.02-2.76; P value for interaction: 0.006). CONCLUSIONS: Despite a moderately strong association between pancreatitis (diagnosed before >2 years) and pancreatic cancer, the population attributable fraction was estimated at 1.34% (95% CI: 0.612-2.07%), suggesting that a relatively small proportion of pancreatic cancer might be avoided if pancreatitis could be prevented.

Alcohol consumption and pancreatic cancer: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4).

BACKGROUND: Heavy alcohol drinking has been related to pancreatic cancer, but the issue is still unsolved. METHODS: To evaluate the role of alcohol consumption in relation to pancreatic cancer, we conducted a pooled analysis of 10 case-control studies (5585 cases and 11,827 controls) participating in the International Pancreatic Cancer Case-Control Consortium. We computed pooled odds ratios (ORs) by estimating study-specific ORs adjusted for selected covariates and pooling them using random effects models. RESULTS: Compared with abstainers and occasional drinkers (< 1 drink per day), we observed no association for light-to-moderate alcohol consumption (≤ 4 drinks per day) and pancreatic cancer risk; however, associations were above unity for higher consumption levels (OR = 1.6, 95% confidence interval 1.2-2.2 for subjects drinking ≥ 9 drinks per day). Results did not change substantially when we evaluated associations by tobacco smoking status, or when we excluded participants who reported a history of pancreatitis, or participants whose data were based upon proxy responses. Further, no notable differences in pooled risk estimates emerged across strata of sex, age, race, study type, and study area. CONCLUSION: This collaborative-pooled analysis provides additional evidence for a positive association between heavy alcohol consumption and the risk of pancreatic cancer.

Cigarette smoking and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (Panc4).

BACKGROUND: To evaluate the dose-response relationship between cigarette smoking and pancreatic cancer and to examine the effects of temporal variables. METHODS: We analyzed data from 12 case-control studies within the International Pancreatic Cancer Case-Control Consortium (PanC4), including 6507 pancreatic cases and 12 890 controls. We estimated summary odds ratios (ORs) by pooling study-specific ORs using random-effects models. RESULTS: Compared with never smokers, the OR was 1.2 (95% confidence interval [CI] 1.0-1.3) for former smokers and 2.2 (95% CI 1.7-2.8) for current cigarette smokers, with a significant increasing trend in risk with increasing number of cigarettes among current smokers (OR=3.4 for ≥35 cigarettes per day, P for trend<0.0001). Risk increased in relation to duration of cigarette smoking up to 40 years of smoking (OR=2.4). No trend in risk was observed for age at starting cigarette smoking, whereas risk decreased with increasing time since cigarette cessation, the OR being 0.98 after 20 years. CONCLUSIONS: This uniquely large pooled analysis confirms that current cigarette smoking is associated with a twofold increased risk of pancreatic cancer and that the risk increases with the number of cigarettes smoked and duration of smoking. Risk of pancreatic cancer reaches the level of never smokers ∼20 years after quitting.

Cigar and pipe smoking, smokeless tobacco use and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (PanC4).

BACKGROUND: Cigarette smoking is the best-characterized risk factor for pancreatic cancer. However, data are limited for other tobacco smoking products and smokeless tobacco. MATERIALS AND METHODS: We conducted a pooled analysis of cigar and pipe smoking and smokeless tobacco use and risk of pancreatic cancer using data from 11 case-control studies (6056 cases and 11,338 controls) within the International Pancreatic Cancer Case-Control Consortium (PanC4). Pooled odds ratios (OR) and the corresponding 95% confidence intervals (CI) were estimated by unconditional multiple logistic regression models adjusted for study center and selected covariates. RESULTS: Compared with never tobacco users, the OR for cigar-only smokers was 1.6 (95% CI: 1.2-2.3), i.e. comparable to that of cigarette-only smokers (OR 1.5; 95% CI 1.4-1.6). The OR was 1.1 (95% CI 0.69-1.6) for pipe-only smokers. There was some evidence of increasing risk with increasing amount of cigar smoked per day (OR 1.82 for ≥ 10 grams of tobacco), although not with duration. The OR for ever smokeless tobacco users as compared with never tobacco users was 0.98 (95% CI 0.75-1.3). CONCLUSION: This collaborative analysis provides evidence that cigar smoking is associated with an excess risk of pancreatic cancer, while no significant association emerged for pipe smoking and smokeless tobacco use.

Highly elevated PSA and dietary PhIP intake in a prospective clinic-based study among African Americans.

African-American men die from prostate cancer (PC) nearly twice as often as white US men and consume about twice as much of the predominant US dietary heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a genotoxic rat-prostate carcinogen found primarily in well-cooked chicken and beef. To investigate the hypothesis that PhIP exposure increases PC risk, an ongoing prospective clinic-based study compared PC screening outcomes with survey-based estimates of dietary PhIP intake among 40-70-year-old African-American men with no prior PC in Oakland, CA. They completed food-frequency and meat-cooking/consumption questionnaires and had a prostate-specific antigen (PSA) test and digital-rectal exam. Results for 392 men indicated a 17 (+/-17) ng/kg day mean (+/-1 s.d.) daily intake of PhIP, about twice that of white US men of similar age. PhIP intake was attributable mostly to chicken (61%) and positively associated (R(2)=0.32, P<0.0001) with saturated fat intake. An odds ratio (95% confidence interval) of 31 (3.1-690) for highly elevated PSA > or =20 ng/ml was observed in the highest 15% vs lowest 50% of estimated daily PhIP intake (> or =30 vs < or =10 ng/kg day) among men 50+ years old (P=0.0002 for trend) and remained significant after adjustment for self-reported family history of (brother or father) PC, saturated fat intake and total energy intake. PSA measures were higher in African-American men with positive family history (P=0.007 all men, P<0.0001 highest PSA quartile). These preliminary results are consistent with a positive association between PhIP intake and highly elevated PSA, supporting the hypothesis that dietary intervention may help reduce PC risk.

Cutaneous melanoma in relation to exogenous hormones and reproductive factors.

Eighty-seven women of ages 37-74, who resided in King County, Wash., and who had been diagnosed between July 1976 and November 1979 as having cutaneous malignant melanoma, were interviewed regarding prior use of estrogen-containing preparations and reproductive history. The responses were compared with those of a random sample of 863 women from the same county. Among the 61 women with superficial spreading melanoma (SSM), use of oral contraceptives for 5 years or more was more common than among controls. The estimated relative risks for users of 5-9 and 10 years or more were 2.4 and 3.6, respectively. No differences between cases and controls were noted for oral contraceptive use of 4 years or less. Giving birth to a first child after age 30 was also associated with an increased relative risk of SSM. Although the positive findings regarding oral contraceptive use and age at birth of first child must be interpreted cautiously pending results of other studies, they suggest that hormonal factors can play a role in the etiology of SSM.

PIP: 87 women ages 37-74 who resided in King County, Washington, and who had been diagnosed between July 1976-November 1979 as having cutaneous malignant melanoma, were interviewed regarding prior use of estrogen-containing preparations and reproductive history. The responses were compared with those of a random sample of 863 women from the same county. Among the 61 women with superficial spreading melanoma (SSM), use of oral contraceptives (OCs) for 5 years or more was more common than among controls. The estimated relative risks for users of 5-9 and 10 years or more were 2.4 and 3.6, respectively. No differences between cases and controls were noted for OC use of 4 or fewer years. Giving birth to a 1st child after age 30 was also associated with an increased relative risk of SSM. Although the positive findings regarding OC use and age at birth of 1st child must be interpreted cautiously pending results of other studies, they suggest that hormonal factors can play a role in SSM etiology.

Major histologic types of cancers of the gum and mouth, esophagus, larynx, and lung by sex and by income level.

Incidence rates by income level were computed for squamous cell carcinomas of the gum and mouth, larynx, and esophagus and for squamous cell carcinoma, small cell carcinoma, and adenocarcinoma of the lung in white males and females aged 35--64 years, with the use of data for the nine geographic areas of the Third National Cancer Survey and the 1970 U.S. census. Within sex, age, and geographic area groups, patterns of cancer incidence by income level were analyzed by use of a nonparametric statistical method. Higher rates for males than for females were found for every histologic type studied, and the ratio of male-to-female rates increased with age (especially for squamous cell carcinomas of the larynx and lung). A strong inverse relation to income level was found for all of the histologic types studied in males and for squamous cell carcinomas of the gum and mouth and esophagus and small cell carcinoma of the lung in females. These findings are discussed with reference to patterns of smoking and alcohol use by sex and social class.

Prevalence and risk factors for anal squamous intraepithelial lesions in women.

BACKGROUND: Anal cancers are thought to arise from squamous intraepithelial lesions in the anal canal, and women infected with human immunodeficiency virus-1 (HIV) may be at higher risk of anal cancer. Our aim was to determine the prevalence of human papillomavirus (HPV)-related abnormalities of the anal canal in women and to characterize risk factors for these lesions. METHODS: We evaluated HPV-related abnormalities in 251 HIV-positive and in 68 HIV-negative women. We completed physical examinations and obtained questionnaire data on medical history and relevant sexual practices. Univariate and adjusted relative risks (RRs) and 95% confidence intervals (CIs) were computed using the Mantel-Haenszel procedure and regression techniques. All statistical tests were two-sided. RESULTS: Abnormal anal cytology, including atypical squamous cells of undetermined significance, low-grade squamous intraepithelial lesions, or high-grade squamous intraepithelial lesions (HSILs), was diagnosed in 26% of HIV-positive and in 8% of HIV-negative women. HSILs were detected by histology or cytology in 6% of HIV-positive and in 2% of HIV-negative women. HIV-positive women showed increased risk of anal disease as the CD4 count decreased (P<.0001) and as the plasma HIV RNA viral load increased (P =.02). HIV-positive women with abnormal cervical cytology had an increased risk of abnormal anal cytology at the same visit (RR = 2.2; 95% CI = 1.4 to 3.3). Abnormal anal cytology in HIV-positive women was associated with anal HPV RNA detected by the polymerase chain reaction and by a nonamplification-based test (RR = 4.3; 95% CI = 1.6 to 11). In a multivariate analysis, the history of anal intercourse and concurrent abnormal cervical cytology also were statistically significantly (P =.05) associated with abnormal anal cytology. CONCLUSIONS: HIV-positive women had a higher risk of abnormal anal cytology than did HIV-negative women with high-risk lifestyle factors. These data provide strong support for anoscopic and histologic assessment and careful follow-up of women with abnormal anal lesions.

Anal cancer incidence: genital warts, anal fissure or fistula, hemorrhoids, and smoking.

We conducted a study of 126 patients with anal and rectal squamous cell carcinoma and 372 randomly selected control subjects in the San Francisco Bay Area (CA) to test the hypothesis that these tumors are related to a history of anal intercourse, the presence of sexually transmitted diseases and other conditions of the anal area, treatment of these diseases or conditions, and history of use of cigarettes or other substances. The relative risk (RR) of cancer was elevated for men with a history of homosexual activity (RR = 12.4, P less than .001). However, after adjustment for other risk factors, this risk was reduced to 2.7 (P = .28). Risk was elevated for homosexual male patients who reported a history of genital warts (RR = 12.6, P = .03), anal fissure or fistula (RR = 9.1, P = .05), and cigarette smoking (RR = 1.9 for 20 pack-yr, P less than .001; RR = 5.2 for 50 pack-yr, P less than .001). (Pack-year is a unit of cigarette use equal to 365 packs.) There was also elevated risk for heterosexual male and female patients who reported a history of genital warts (RR = 4.4, P = .003), anal fissure or fistula (RR = 2.4, P = .03), and more than 12 episodes of hemorrhoids (RR = 2.6, P less than .001). These findings suggest that anal cancer risk is etiologically related to human papillomaviruses that cause genital warts. In addition, constant irritation, chronic inflammatory changes, and repeated epithelial regeneration that accompany noninfectious conditions may be related to risk of anal cancer. The higher risk among homosexual men is related to the higher prevalence of anal cancer risk factors for this group.

Mycosis fungoides in relation to environmental exposures and immune response: a case-control study.

Mycosis fungoides is a cutaneous T-cell lymphoma of unknown etiology, thought to be a rare sequela of chronic antigenic stimulation that may occur, for example, with exposure to contact allergens. To explore this possibility, we interviewed 174 patients with mycosis fungoides and 294 randomly selected control subjects in the San Francisco, Los Angeles, and Seattle areas concerning their lifetime histories of employment, chemical exposures, allergy, atopy, and certain medical conditions. Patients reported higher prevalence of cancers other than the non-Hodgkin's lymphomas and skin cancers (relative risk = 3.3, P less than .001) and were more likely than controls to burn when exposed to the sun (for nonblacks, relative risk = 1.7, P = .01). The latter difference may reflect a manifestation rather than a precursor of the disease. We found no consistent or biologically plausible differences between patients and controls with respect to types of jobs held, or to occupational or vocational exposures to chemicals. These findings do not support the hypothesis that persistent antigenic stimulation by contact allergens is etiologically important in the pathogenesis of mycosis fungoides.

Mutagenic mucus in the cervix of smokers.

A pilot study was conducted to determine whether any relationship exists between mutagenicity of a women's uterine cervical mucus and her current smoking status. Cervical fluids obtained from 78 premenopausal women seen between July 1983 and March 1984 at the University of California, San Francisco Dysplasia (and diethylstilbestrol) Clinic or in a private practice were tested for mutagenicity by means of the Ames-Salmonella microsomal test. Of 36 current smokers, 14 (39%) had positive tests as compared to 5 of 42 nonsmokers (12%). The odds ratio (OR) estimate was 4.7 with 95% confidence limits (CL) of 1.6-14.2. Secretions from 14 of 32 (44%) women who had smoked during the day of the sample collection--within the previous 7 hours--were positive on the laboratory test, whereas none of the 4 women was positive who had smoked 8 hours or more before the specimens were obtained. Fluids from women with dysplasia or carcinoma in situ were more likely to be mutagenic than were those from other women, although this finding may be due to chance (OR = 2.0 with 95% CL of .70-5.9). This relationship between smoking and mutagenic cervical fluids offers evidence that might help to explain the association between cervical cancer and cigarette smoking noted in previous epidemiologic studies.

Uveal melanoma, hormonal and reproductive factors in women.

In a case-control study, we explored a potential association between uveal melanoma and reproductive factors in women. Responses from telephone interviews of 186 women diagnosed with uveal melanoma were compared with responses of 423 women without this disease. All women resided in 11 U.S. western states. We observed a decreased risk of uveal melanoma for women who had ever been pregnant [relative risk (RR) = 0.60, 95% confidence interval (CI) = 0.37 -0.95], with an increase in this protective effect with more live births after adjustment for age, menopausal status, eye color, and skin sensitivity to the sun (1-2 births, RR = 0.47,95% CI 0.29-0.78; 3-4 births, RR = 0.38, 95% CI = 0.22-0.64; 5 or more births, RR = 0.33, 95% CI = 0.15-0.71). The largest effect was observed between nulliparous and parous women. No other reproductive factors, including use of oral contraceptives or postmenopausal estrogens, were shown to be related to risk for uveal melanoma. We conclude that most reproductive factors in this population play little or no role in the etiology of uveal melanoma. The association with number of live births must be confirmed in other studies to assure that it is unrelated to confounding factors not measured in this study.

Uveal melanoma in relation to ultraviolet light exposure and host factors.

We conducted a case-control interview study among 1277 subjects (407 patients, 870 controls selected by using random digit dial) in 11 western United States to determine whether uveal melanoma and cutaneous melanoma shared common risk factors. After adjustment for other factors, the risk of uveal melanoma was increased for those with green, gray, or hazel eyes [relative risk (RR) = 2.5, P less than 0.001] or blue eyes (RR = 2.2, P less than 0.001) when compared to brown. A tendency to sunburn after 0.5 h midday summer sun exposure increased risk for uveal melanoma (burn with tanning RR = 1.5, P = 0.02; burn with little tanning RR = 1.8, P less than 0.001; burn with no tanning RR = 1.7, P = 0.002); as did exposure to UV or black lights (RR = 3.7, P = 0.003); and welding burn, sunburn of the eye, or snow blindness (RR = 7.2, P less than 0.001). An association with uveal melanoma was also noted with an increasing number of large nevi (P = 0.04 for trend), although the individual risk estimates were not remarkable. These data suggest that host factors and exposure to UV light are risk factors for uveal melanoma.

Detection of human papillomavirus DNA in anal intraepithelial neoplasia and anal cancer.

Forty anal paraffin-embedded tissue specimens from 24 subjects were studied for the presence of human papillomavirus (HPV) types 6, 11, 16, 18, 31, and 33, herpes simplex virus (HSV), Epstein-Barr virus, and cytomegalovirus DNA by using the polymerase chain reaction. These tissues ranged from histologically normal to invasive squamous cell carcinoma. HPV DNA was detected in the invasive anal cancer tissues of 11 of 13 subjects. HPV types were segregated by histopathological severity, with HPV 16 associated exclusively with high grade anal intraepithelial neoplasia and invasive cancer. HPV types 6 and 11 were associated with condyloma and low grade anal intraepithelial neoplasia. HPV DNA in situ hybridization studies confirmed the presence of HPV DNA in the invasive cancer tissues of 6 of 12 subjects. HPV DNA in these tissues was highly focal and primarily associated with invasive cell nests that demonstrated the greatest degree of squamous differentiation. HSV DNA was detected only in association with advanced disease, being found in the cancer tissues of 5 of 13 subjects, and in 3 of 4 subjects with high grade anal intraepithelial neoplasia, but was not detected by in situ hybridization. Epstein-Barr virus and cytomegalovirus DNA were not detected in the 40 tissue specimens. We conclude that HPV infection may play an important role in the pathogenesis of anal cancer. The association between HSV infection and high grade anal disease suggests that HSV infection may also play a role in disease progression.