Relationship between human papillomavirus infection and tumours of anogenital sites other than the cervix.

Although tissues in the case series of anal, penile, vaginal and vulvar neoplasms that have looked for evidence of HPV infection by probing for HPV DNA have been selected for convenience, they support the view that HPV, especially type 16, is associated with approximately 50% of these tumours. A higher percentage of the anal, vaginal and vulvar tumours are associated with HPV 16 than are penile tumours. This discrepancy may be due to the low number of penile tumours studied or to a true difference in the proportion of penile cancer cases related to HPV. HPV 6/11 and 18 are found less frequently at all anatomic sites. About 10% of tumours that are probed for these viruses are positive, although there are some notable exceptions such as a study that found 39% of penile tumours positive for type 18 and a study that found approximately two thirds of vulvar tumours positive for HPV 18 using Southern blot hybridization. For all of these tumours, there is likely to be a subset of the cases who develop their cancer through mechanisms that do not involve HPV. The case-control studies found a strong association with genital warts, number of sexual partners and, with the exception of vaginal cancer, smoking and/or heavy smoking at the time of diagnosis of the disease. A history of genital warts, smoking at diagnosis, and seropositivity to HSV2 are exposures that have also been found to be associated with cervical cancer. A population-based case-control study in western Washington and Vancouver, British Columbia that studied all anogenital cancers found that a history of genital warts was stronger among patients with vulvar, anal, vaginal and penile cancer than among those with cervical cancer. This was also true of smoking at diagnosis, with the exception of vaginal cancer, where there was little excess risk. This study and other supporting data indicate that these anogenital tumours share many of the same risk factors as cervical cancer.     

Chronic lymphocytic leukemia in relation to chemical exposures

As part of a population-based case-control study carried out in four areas of the United States, 427 cases of chronic lymphocytic leukemia diagnosed between July 1, 1977, and December 31, 1981, and 1,683 controls were interviewed regarding their history of chemical exposure. Respondents were asked if they had ever been "highly exposed" at home, at work, or elsewhere to one or more of a list of chemicals or to any other such substances not on the list. These chemicals were categorized into 20 exposure groups based on chemical composition. Odds ratios were calculated adjusting for age, sex, race, education level, and geographic location by means of unconditional logistic regression. Increased risks were associated with reported past exposure to acid-containing chemicals, "other caustic substances," aliphatic hydrocarbons, and chlorinated hydrocarbons. Because of the large number of exposures investigated in this study, and because of the relatively imprecise means the authors had to assess exposure, further research is needed to verify these findings.     

Maternal smoking and Down syndrome: the confounding effect of maternal age

Inconsistent results have been reported from studies evaluating the association of maternal smoking with birth of a Down syndrome child. Control of known risk factors, particularly maternal age, has also varied across studies. By using a population-based case-control design (775 Down syndrome cases and 7,750 normal controls) and Washington State birth record data for 1984-1994, the authors examined this hypothesized association and found a crude odds ratio of 0.80 (95% confidence interval 0.65-0.98). Controlling for broad categories of maternal age (<35 years, > or =35 years), as described in prior studies, resulted in a negative association (odds ratio = 0.87, 95% confidence interval 0.71-1.07). However, controlling for exact year of maternal age in conjunction with race and parity resulted in no association (odds ratio = 1.00, 95% confidence interval 0.82-1.24). In this study, the prevalence of Down syndrome births increased with increasing maternal age, whereas among controls the reported prevalence of smoking during pregnancy decreased with increasing maternal age. There is a substantial potential for residual confounding by maternal age in studies of maternal smoking and Down syndrome. After adequately controlling for maternal age in this study, the authors found no clear relation between maternal smoking and the risk of Down syndrome.     

The relationship of placenta previa and history of induced abortion.

OBJECTIVES: We evaluated the risk of placenta previa being associated with a history of induced abortion by different surgical procedures. METHODS: Cases (n=192) were women who had a singleton delivery complicated by placenta previa at a major obstetric care hospital in western Washington state between April 1, 1990 and December 31, 1992. Controls (n=622) were women with singleton deliveries not complicated by placenta previa or abruption. Odds ratios, determined by logistic regression, approximate the relative risks. RESULTS: Vacuum aspiration abortion was not associated with an increased risk of placenta previa (OR 0.9, 95% CI 0.6-1.5). However, the risk of placenta previa increased with the number of sharp curettage abortions (OR 2.9, 95% CI 1.0-8.5 for > or =3). CONCLUSIONS: Risk of placenta previa may be increased in a dose response fashion by multiple sharp curettage abortions. However, vacuum aspiration does not confer an increased risk, and may be a better alternative.     

Alcohol exposure and breast cancer: results of the women's contraceptive and reproductive experiences study.

OBJECTIVES: To explore associated biological outcomes and clarify the role of timing of exposure in the alcohol-breast cancer relationship.METHODS: In a population-based study of 4,575 women ages 35 to 64 years diagnosed with invasive breast cancer between 1994 and 1998 and 4,682 controls, we collected details of lifetime alcohol use and factors that could confound or modify the alcohol-breast cancer relationship. We used conditional logistic regression to compute the odds of breast cancer among drinkers relative to nondrinkers at all ages and at ages 35 to 49 and 50 to 64 years separately.RESULTS: Recent consumption (at reference age minus two) of >/=7 drinks per week was associated with increased risk [odds ratio (OR), 1.2; 95% CI, 1.01-1.3] and evidence of dose response was observed. Most of the excess was observed among women ages 50-64 years (OR 1.3; 95% CI, 1.1-1.6), although the test for age interaction was not statistically significant. Exposure later in life seemed more important than early exposure. Excess breast cancer associated with recent consumption was restricted to localized disease. When outcome was examined according to tumor hormone receptor status, highest risks were observed for estrogen receptor-positive/progesterone receptor-negative tumors (OR 1.6; 95% CI, 1.2-2.3).CONCLUSIONS: The effect of timing of alcohol exposure on breast cancer risk is complicated and will require additional study focused on this one issue. Further work is needed to explain how alcohol exposure, sex hormones, and tumor receptor status interact.     

Case-control differences in the reliability of reporting a history of induced abortion

The authors investigated the possibility that, in interview-based case-control studies, controls are more likely than cases to underreport a history of induced abortion. A case-control study was conducted in White women under 45 years of age who had given birth in Washington State during 1984-1994. The cases were women in three metropolitan counties of Washington State diagnosed with invasive breast cancer during 1984-1994; controls were selected through random digit dialing. A history of induced abortion among study participants was compared between interview data and information collected on the birth record of the last child to whom they gave birth (225 cases, 303 controls). Among women with a prior induced abortion recorded on the birth record, 14.0% of the 43 cases and 14.9% of the 47 controls did not report an induced abortion at interview (difference = -0.9%, 95% confidence interval of the difference: -15, 14). The authors' data do not suggest that controls are more reluctant to report a history of induced abortion than are women with breast cancer.     

Basophil activation through ASGM1 stimulation triggers PAF release and anaphylaxis‐like shock in mice

Basophils have been shown to contribute to anaphylaxis through either an IgE–FcεRI‐dependent pathway or an IgG–FcγR pathway. However, it remains largely unclear whether basophils can be activated to promote anaphylaxis via a non‐FcR pathway as well. The glycolipid receptor ASGM1 (Asialoganglioside gangliotetraosylceramide), which has an exposed GalNAcβ1–4Gal moiety and serves as a receptor for pathogen associated molecular patterns such as flagellin, was recently found to be expressed on basophils. Here, we demonstrate that stimulation of basophils with anti‐ASGM1 antibodies promotes platelet‐activating factor (PAF) secretion in vitro and in vivo. Moreover, we found that ASGM1 stimulation triggers basophil‐ and PAF‐dependent anaphylactic shock in pertussis toxin (PTX)‐pretreated mice. Thus, ASGM1 has a crucial role in basophil activation and basophil‐mediated anaphylaxis‐like shock in mice, especially when the vascular permeability is increased by PTX treatment. Our findings describe a novel anaphylaxis‐associated pathway that is antigen‐, antibody‐, and FcR‐independent.     

Cervical and vulvar cancer risk in relation to the joint effects of cigarette smoking and genetic variation in interleukin 2

Cigarette smoking is an established cofactor to human papillomavirus (HPV) in the development of cervical and vulvar squamous cell carcinoma (SCC), and may influence risk through an immunosuppressive pathway. Genetic variation in interleukin 2 (IL2), associated in some studies with the inhibition of HPV-targeted immunity, may modify the effect of smoking on the risk of HPV-related anogenital cancers. We conducted a population-based case-only study to measure the departure from a multiplicative joint effect of cigarette smoking and IL2 variation on cervical and vulvar SCC. Genotyping of the four IL2 tagSNPs (rs2069762, rs2069763, rs2069777, and rs2069778) was done in 399 cervical and 486 vulvar SCC cases who had been interviewed regarding their smoking history. Compared with cases carrying the rs2069762 TT genotype, we observed significant departures from multiplicativity for smoking and carriership of the TG or GG genotypes in vulvar SCC risk [interaction odds ratio (IOR), 1.67; 95% confidence interval (CI), 1.16-2.41]. Carriership of one of three diplotypes, together with cigarette smoking, was associated with either a supramultiplicative (TGCT/GGCC; IOR, 2.09; 95% CI, 0.98-4.46) or submultiplicative (TTCC/TGTC; IOR, 0.37; 95% CI, 0.16-0.85 or TGCT/TGCC; IOR, 0.37; 95% CI, 0.15-0.87) joint effect in vulvar cancer risk. For cervical SCC, departure from multiplicativity was observed for smokers homozygous for the rs2069763 variant allele (TT versus GG or GT genotypes; IOR, 1.87; 95% CI, 1.00-3.48), and for carriership of the TTCC/TTCC diplotype (IOR, 2.08; 95% CI, 1.01-4.30). These results suggest that cervical and vulvar SCC risk among cigarette smokers is modified by genetic variation in IL2.     

Functional ovarian cysts in relation to the use of monophasic and triphasic oral contraceptives.

This population-based case-control study assessed the effect of current use of monophasic or triphasic oral contraceptives (OCs) on the risk of functional ovarian cyst development. The cases were all 15-39-year-old enrollees in the Group Health Cooperative of Puget Sound who had either an inpatient primary diagnosis of functional ovarian cyst in 1988 or 1989 (N = 67) or an outpatient primary diagnosis of functional ovarian cyst from March 1988 through August 1989 at one of five Group Health Cooperative primary care clinics (N = 39). Controls were randomly selected enrollees matched to the cases for age, primary care clinic, and enrollment date (N = 255). Subjects with previous hysterectomy or oophorectomy were excluded from this analysis. Pharmacy and medical record review showed that 16% of cases and 19% of controls were currently using monophasic OCs, whereas 11% of cases and 9% of controls were using triphasic OCs. Compared with women not using hormonal contraception, the relative risks of a diagnosed functional ovarian cyst among women currently using OCs were 0.8 (95% confidence interval [CI] 0.4-1.8) for users of monophasic OCs and 1.3 (95% CI 0.5-3.3) for users of triphasic OCs. In contrast to previous studies of monophasic OCs containing higher steroid dosages, the results of this study suggest that current use of low-dose monophasic OCs does not substantially decrease a woman's risk of functional ovarian cyst formation. In addition, our results do not support recent speculation that current use of triphasic OCs appreciably increases the risk of functional ovarian cysts.     

Risk of papillary thyroid cancer in women in relation to smoking and alcohol consumption

Both smoking and alcohol consumption may influence thyroid function, although the nature of these relations is not well understood. We examined the influence of tobacco and alcohol use on risk of papillary thyroid cancer in a population-based case-control study. Of 558 women with thyroid cancer diagnosed during 1988-1994 identified as eligible, 468 (83.9%) were interviewed; this analysis was restricted to women with papillary histology (N = 410). Controls (N = 574) were identified by random digit dialing, with a response proportion of 73.6%. We used logistic regression to calculate odds ratios (OR) and associated confidence intervals (CI) estimating the relative risk of papillary thyroid cancer associated with cigarette smoking and alcohol consumption. A history of ever having smoked more than 100 cigarettes was associated with a reduced risk of disease (OR = 0.7, 95% CI = 0.5-0.9). This reduction in risk was most evident in current smokers (OR = 0.5, 95% CI = 0.4-0.7). Women who reported that they had ever consumed 12 or more alcohol-containing drinks within a year were also at reduced risk (OR 0.7, 95% CI = 0.5-1.0). Similar to the association noted with smoking, the reduction in risk was primarily present among current alcohol consumers. The associations we observed, if not due to chance, may be related to actions of cigarette smoking and alcohol consumption that reduce thyroid cell proliferation through effects on thyroid stimulating hormone, estrogen, or other mechanisms.