Use of Immunosuppression and the Risk of Subsequent Overall or Cancer Mortality.

PURPOSE: To determine the incidence of all-cause and cancer mortality (CM) in association with immunosuppression. DESIGN: Retrospective cohort study at ocular inflammatory disease (OID) subspecialty centers. We harvested exposure and covariate data retrospectively from clinic inception (earliest in 1979) through 2010 inclusive. Then we ascertained overall and cancer-specific mortalities by National Death Index linkage. We constructed separate Cox models to evaluate overall and CM for each class of immunosuppressant and for each individual immunosuppressant compared with person-time unexposed to any immunosuppression. PARTICIPANTS: Patients with noninfectious OID, excluding those with human immunodeficiency infection or preexisting cancer. METHODS: Tumor necrosis factor (TNF) inhibitors (mostly infliximab, adalimumab, and etanercept); antimetabolites (methotrexate, mycophenolate mofetil, azathioprine); calcineurin inhibitors (cyclosporine); and alkylating agents (cyclophosphamide) were given when clinically indicated in this noninterventional cohort study. MAIN OUTCOME MEASURES: Overall mortality and CM. RESULTS: Over 187 151 person-years (median follow-up 10.0 years), during which 15 938 patients were at risk for mortality, we observed 1970 deaths, 435 due to cancer. Both patients unexposed to immunosuppressants (standardized mortality ratio [SMR] = 0.95, 95% confidence interval [CI], 0.90-1.01) and those exposed to immunosuppressants but free of systemic inflammatory diseases (SIDs) (SMR = 1.04, 95% CI, 0.95-1.14) had similar mortality risk to the US population. Comparing patients exposed to TNF inhibitors, antimetabolites, calcineurin inhibitors, and alkylating agents with patients not exposed to any of these, we found that overall mortality (adjusted hazard ratio [aHR] = 0.88, 0.89, 0.90, 1.11) and CM (aHR = 1.25, 0.89, 0.86, 1.23) were not significantly increased. These results were stable in sensitivity analyses whether excluding or including patients with SID, across 0-, 3-, or 5-year lags and across quartiles of immunosuppressant dose and duration. CONCLUSIONS: Our results, in a cohort where the indication for treatment was proven unassociated with mortality risk, found that commonly used immunosuppressants-especially the antimetabolites methotrexate, mycophenolate mofetil, and azathioprine; the TNF inhibitors adalimumab and infliximab, and cyclosporine-were not associated with increased overall and CM over a median cohort follow-up of 10.0 years. These results suggest the safety of these agents with respect to overall and CM for patients treated with immunosuppression for a wide range of inflammatory diseases. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Awareness and use of genetic testing: An analysis of the Health Information National Trends Survey 2020.

PURPOSE: Genetic testing is a tool used in a variety of settings for medical and nonhealth related purposes. The goal of this analysis was to better understand the awareness and use of genetic testing in the United States. METHODS: Data from the 2020 Health Information National Trends Survey 5 cycle 4 were used to assess the awareness and use of genetic testing by demographic characteristics, personal cancer history, and family cancer history. RESULTS: Overall, 75% of participants were aware of genetic testing and 19% of participants had genetic testing. Ancestry testing was the most common type of testing that the participants were aware of and had received. Non-Hispanic Asian, Non-Hispanic Black, and Hispanic respondents and participants with incomes less than $20,000 were less likely to be aware of and have received any type of genetic testing than the Non-Hispanic White participants and participants with higher income, respectively. Participants with a family history of cancer were more likely to be aware of cancer genetic testing than those without, and participants with a personal history of cancer were more likely to have had cancer genetic testing. CONCLUSION: It appears awareness of genetic testing is increasing in the United States, and differences in awareness persist by race/ethnicity and income.

Anti-Müllerian hormone and risk of ovarian cancer in nine cohorts.

Animal and experimental data suggest that anti-Müllerian hormone (AMH) serves as a marker of ovarian reserve and inhibits the growth of ovarian tumors. However, few epidemiologic studies have examined the association between AMH and ovarian cancer risk. We conducted a nested case-control study of 302 ovarian cancer cases and 336 matched controls from nine cohorts. Prediagnostic blood samples of premenopausal women were assayed for AMH using a picoAMH enzyme-linked immunosorbent assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable-adjusted conditional logistic regression. AMH concentration was not associated with overall ovarian cancer risk. The multivariable-adjusted OR (95% CI), comparing the highest to the lowest quartile of AMH, was 0.99 (0.59-1.67) (Ptrend : 0.91). The association did not differ by age at blood draw or oral contraceptive use (all Pheterogeneity : ≥0.26). There also was no evidence for heterogeneity of risk for tumors defined by histologic developmental pathway, stage, and grade, and by age at diagnosis and time between blood draw and diagnosis (all Pheterogeneity : ≥0.39). In conclusion, this analysis of mostly late premenopausal women from nine cohorts does not support the hypothesized inverse association between prediagnostic circulating levels of AMH and risk of ovarian cancer.

Anti-Mullerian hormone and endometrial cancer: a multi-cohort study.

BACKGROUND: The Mullerian ducts are the embryological precursors of the female reproductive tract, including the uterus; anti-Mullerian hormone (AMH) has a key role in the regulation of foetal sexual differentiation. Anti-Mullerian hormone inhibits endometrial tumour growth in experimental models by stimulating apoptosis and cell cycle arrest. To date, there are no prospective epidemiologic data on circulating AMH and endometrial cancer risk. METHODS: We investigated this association among women premenopausal at blood collection in a multicohort study including participants from eight studies located in the United States, Europe, and China. We identified 329 endometrial cancer cases and 339 matched controls. Anti-Mullerian hormone concentrations in blood were quantified using an enzyme-linked immunosorbent assay. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) across tertiles and for a doubling of AMH concentrations (ORlog2). Subgroup analyses were performed by ages at blood donation and diagnosis, oral contraceptive use, and tumour characteristics. RESULTS: Anti-Mullerian hormone was not associated with the risk of endometrial cancer overall (ORlog2: 1.07 (0.99-1.17)), or with any of the examined subgroups. CONCLUSIONS: Although experimental models implicate AMH in endometrial cancer growth inhibition, our findings do not support a role for circulating AMH in the aetiology of endometrial cancer.

Pre-diagnosis insulin-like growth factor-I and risk of epithelial invasive ovarian cancer by histological subtypes: A collaborative re-analysis from the Ovarian Cancer Cohort Consortium.

PURPOSE: Biologic evidence suggests that the Insulin-like growth factor (IGF)-family may be involved in the etiology of epithelial invasive ovarian cancer (EOC). However, prospective studies investigating the role of IGF-I in ovarian carcinogenesis have yielded conflicting results. METHODS: We pooled and harmonized data from 6 case-control studies nested within the Ovarian Cancer Cohort Consortium to investigate the association between pre-diagnosis IGF-I concentrations and subsequent risk of EOC. We evaluated IGF-I concentrations and risk of EOC overall and by tumor subtype (defined by histology, grade, stage) in 1,270 cases and 2,907 matched controls. Multivariable conditional logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Doubling of IGF-I concentration was associated with significantly lower risk of overall EOC [ORlog2 = 0.82; CI 0.72-0.93]. We observed no heterogeneity by tumor characteristics (e.g., histology, p het = 0.62), menopausal status at blood collection (p het = 0.79), or age at diagnosis (p het = 0.60). CONCLUSIONS: These results suggest that IGF-I concentrations are inversely associated with EOC risk, independent of histological phenotype. Future prospective research should consider potential mechanisms for this association, including, considering other members of the IGF-family to better characterize the role of IGF-signaling in the etiology of EOC.

A prospective study of aromatase inhibitor therapy initiation and self-reported side effects.

PURPOSE: The objective of this study was to examine the associations between aromatase inhibitors (AIs) and side effects less frequently reported in the literature, including difficulty concentrating, forgetfulness, hair loss, and numbness in the extremities. METHODS: Data were analyzed from a cohort of 146 breast cancer patients initiating AI therapy and followed for 1 year and a cohort of 144 postmenopausal women without a history of cancer followed for 6 months. At baseline (prior to AI therapy for breast cancer patients), and at 3 months, 6 months, and 1 year (for breast cancer patients only), a comprehensive questionnaire was administered that ascertained data on symptoms. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using logistic regression for new onset of symptoms among the breast cancer patients compared to the women without a history of cancer. RESULTS: Among the breast cancer patients, 34.2% were treated with chemotherapy prior to AI treatment. Over the first 6 months of AI treatment, breast cancer patients had significantly higher odds of reporting new onset of forgetfulness (OR 4.00; 95% CI 1.67, 9.59), difficulty concentrating (OR 2.73; 95% CI 1.29; 5.78), hair loss (OR 4.12; 95% CI 1.86, 9.17), and numbness/tingling in the extremities (OR 2.47; 95% CI 1.09, 5.62) compared to women without a history of cancer. Similar increases in odds were observed for the subgroup of women not treated with chemotherapy versus the comparison group. CONCLUSIONS: AI-related symptoms should be monitored and addressed so that adherence to therapy is maintained.

Cardiovascular Health among Black and White Breast Cancer Patients Initiating Aromatase Inhibitor Therapy.

The purpose of this study was to compare the cardiovascular health of Black and White breast cancer patients undergoing adjuvant treatment. Baseline data from a cohort study of Black (n = 45) and White (n = 101) breast cancer patients initiating aromatase inhibitor treatment were analyzed. Participants had a cardiovascular health assessment, including carotid intimal medial thickness measurement, donated a blood sample, and completed a questionnaire. Atherosclerotic cardiovascular disease (ASCVD) event risk scores were calculated. Compared to their White counterparts, the Black patients had a significantly higher median ASCVD risk score (p = 0.009) and had a higher number of CVD risk factors (p < 0.05). Black patients were also more likely to have hypertension, diabetes, or to be obese than the White participants. The prevalence of cardiovascular disease and cardiovascular disease risk factors among Black and White breast cancer patients is high, and racial disparities exist which may have treatment implications.

Interleukin-6 and risk of colorectal cancer: results from the CLUE II cohort and a meta-analysis of prospective studies.

PURPOSE: The association between prediagnostic interleukin-6 (IL-6) concentrations and risk of colorectal cancer was evaluated in a nested case-control study and a meta-analysis of prospective studies. METHODS: Colorectal cancer cases (n = 173) and matched controls (n = 345) were identified between 1989 and 2000 among participants in the CLUE II cohort of Washington Country, Maryland. Matched odds ratios and the corresponding 95 % confidence intervals (CIs) were estimated using conditional logistic regression models. RESULTS: Participants in the highest third of plasma IL-6 concentration had a 2.48 times higher risk of colon cancer compared to participants in the bottom third (95 % CI 1.26-4.87; p-trend 0.02) after multivariate adjustment. This association did not differ according to the stage of disease, age, sex, or other potential modifying variables and remained statistically significant after adjustment for C-reactive protein concentrations. No statistically significant association was observed for rectal cancer risk. The meta-analysis of six prospective studies yielded an increased but borderline statistically significant risk of colon cancer per 1 U increase in naturally logarithm-transformed IL-6 (summary RR 1.22; 95 % CI 1.00-1.49; I (2) 46 %). An inverse association was noted for rectal cancer (RR 0.69; 95 % CI 0.54-0.88; I (2) 0 %), but there was evidence for small-study effects (p 0.02). CONCLUSION: Our findings provide support for a modest positive association between IL-6 concentrations and colon cancer risk. More work is needed to determine whether IL-6 is a valid marker of colorectal inflammation and whether such inflammation contributes to colon and rectal cancer risk.

Musculoskeletal pain and health-related quality of life among breast cancer patients treated with aromatase inhibitors.

OBJECTIVE: This study aims to examine the associations between musculoskeletal pain and health-related quality of life (HR-QOL) among breast cancer patients on aromatase inhibitors (AIs) and women without a history of breast cancer. METHODS: A cross-sectional study was conducted among 68 breast cancer patients on AIs for an average of 3.5 years and 137 postmenopausal women without a history of cancer. Musculoskeletal pain was assessed using a 10-cm visual analog scale; HR-QOL was examined using the Medical Outcomes Study Short Form (SF-36) health survey. Linear regression was used to estimate the associations between pain and HR-QOL in both groups. RESULTS: Approximately 64 % of the breast cancer patients and women in the comparison group reported musculoskeletal pain. Among women with breast cancer, those with pain had significantly lower HR-QOL scores in the physical (52.2 vs. 42.6; p < 0.001) and mental (52.7 vs. 45.5; p = 0.01) component summary scores compared with those without pain. In the comparison group, pain was associated with significantly lower scores in the physical (55.4 vs. 46.0; p < 0.001), but not the mental, component summary score (52.1 vs. 52.4; p = 0.82). The significant associations between pain and HR-QOL persisted after confounder adjustment in both groups. Among women with similar severity of pain, breast cancer patients reported significantly lower HR-QOL in the mental summary component compared with the women in the comparison group. CONCLUSIONS: Among breast cancer patients, musculoskeletal pain adversely affects both mental and physical components of HR-QOL. Preventing or treating AI-associated musculoskeletal pain may improve overall HR-QOL among breast cancer patients treated with AIs.

Capitalizing on the "teachable moment" to promote healthy dietary changes among cancer survivors: the perspectives of health care providers.

PURPOSE: Although cancer is often thought of as a teachable moment, many cancer survivors do not adhere to behavioral recommendations that might improve their health. This study explored health care providers' perspectives on the importance and feasibility of addressing behavior change, specifically healthy diet, with cancer survivors. METHODS: In-depth interviews were conducted with 33 health care providers who care for posttreatment survivors of breast cancer, prostate cancer, and non-Hodgkin's lymphoma. Interviews were analyzed thematically. RESULTS: Health care providers emphasized the strength of evidence linking diet/obesity to recurrence in their assessment of the importance of promoting dietary change among their survivor patients. Cancer specialists (e.g., oncologists, surgeons) generally brought up dietary change with patients if they considered the evidence to be strong. In contrast, primary care providers viewed health promotion as important for all patients and reported treating cancer survivor patients the same as others when it came to making dietary recommendations. There was a lack of consensus among providers on the best timing to bring up behavior change. Providers described specific subgroups of patients who they saw as more motivated to make behavior changes and patient barriers to making dietary changes. CONCLUSIONS: Health care providers can play an important role in promoting healthy diet among cancer survivors. As the evidence base around diet and cancer recurrence/prognosis grows, it is important that this information is communicated to providers. Strategies such as incorporating behavior change messages into survivor care plans may help standardize recommendations to survivors.

Change in Pain and Quality of Life Among Women Enrolled in a Trial Examining the Use of Narrow Band Imaging During Laparoscopic Surgery for Suspected Endometriosis.

STUDY OBJECTIVE: To examine whether the addition of narrow band imaging (NBI) to traditional white light imaging during laparoscopic surgery impacts pain and quality of life (QOL) at 3 and 6 months after surgery among women with suspected endometriosis and/or infertility. DESIGN: A randomized controlled trial (Canadian Task Force classification level I). SETTING: The trial was conducted in 2 medical centers. PATIENTS: From October 2011 to November 2013, 167 patients undergoing laparoscopic examination for suspected endometriosis and/or infertility were recruited. The analytic study sample includes 148 patients with pain and QOL outcome data. INTERVENTIONS: Patients were randomized in a 3:1 ratio to receive white light imaging followed by NBI (WL/NBI) or white light imaging only (WL/WL). MEASUREMENTS AND MAIN RESULTS: Questionnaires were administered at baseline and at 3- and 6-month follow-up time points. Average and most severe pain at each time point were assessed using a 10-cm visual analog scale. QOL was measured using the Endometriosis Health Profile-30. Baseline characteristics were similar for the study groups. The WL/NBI and WL/WL groups had similar reductions in pain at 3 and 6 months. In addition, QOL improved similarly for both the WL/NBI and WL/WL groups at 3 and 6 months. CONCLUSION: Laparoscopic surgery for suspected endometriosis is associated with a reduction in pain and an improvement in QOL. The differences in pain reduction and QOL improvement, which are noted at 3 months and remain stable at 6 months after surgery, are similar for those undergoing surgery with WL/NBI compared with those undergoing surgery under traditional white light conditions.

Sensitivity of Narrow Band Imaging Compared With White Light Imaging for the Detection of Endometriosis.

STUDY OBJECTIVE: To evaluate the ability of narrow band imaging (NBI) in conjunction with standard white light imaging to improve the detection and diagnosis of endometriosis during laparoscopic evaluation compared with white light imaging alone. Sensitivity of NBI in detecting endometriosis was assessed and compared with white light imaging. DESIGN: Randomized controlled trial. CLASSIFICATION OF STUDY DESIGN: LEVEL I: Evidence obtained from a properly designed, randomized, controlled trial. SETTING: The trial was conducted in 2 medical centers. PATIENTS: One hundred sixty-seven women undergoing laparoscopic evaluation for suspected endometriosis and/or infertility were recruited. Of these, 150 were assessable to determine sensitivity of NBI compared with white light imaging for the detection of endometriotic lesions. INTERVENTIONS: Patients were randomized in a 3:1 ratio to receive white light imaging followed by NBI or white light imaging only. The pelvis was systematically visualized with each assigned imaging modality; lesions were recorded under each visualization and then resected. All patients had white light imaging on the first visualization followed by either a second white light examination (control arm) or NBI examination (intervention arm). MEASUREMENTS: Pathology of resected lesions was the criterion standard for evaluating sensitivity and was conducted at each institution. The method of detection of the lesion (white light or NBI) was masked. Central pathology review was conducted for a randomly selected 10% sample of specimens and for those lesions visualized under only 1 imaging modality among patients assigned to the intervention arm. The sensitivity was assessed for each modality (white light and NBI) and compared using a McNemar's test. MAIN RESULTS: Among the group randomized to receive both white light and NBI, 4 patients had lesions detected with NBI but no lesions detected with white light. Among the 255 lesions confirmed as endometriosis by pathologic review, all were detected by NBI for a sensitivity of 100%; 79% were detected by white light imaging (p < .001). CONCLUSION: The addition of NBI to white light imaging increased the number of endometriotic lesions identified during laparoscopy and the diagnosis of endometriosis compared with the use of white light imaging alone.

Racial differences in depressive symptoms and self-rated health among breast cancer survivors on aromatase inhibitor therapy.

The goal of this survey-based study was to examine whether aromatase inhibitor (AI) therapy was associated with depressive symptoms and self-rated health among Black and White breast cancer survivors (N = 761). Results showed that among Black, but not White, breast cancer survivors current AI therapy was associated with a significant increase in the odds of both depressive symptoms (OR 3.59; 95% CI 1.01, 13.00) and poorer self-rated health (OR 3.16; 95% CI 1.06, 9.46). Presence of pain was significantly associated with increased odds of both outcomes among both groups. The findings underscore the importance of addressing not only physical but mental health among breast cancer survivors on AIs, especially those of Black race.

A Qualitative Description of a Family Intervention for Breast Cancer Survivors Experiencing Fatigue.

Breast cancer survivors commonly experience fatigue, but family-focused interventions as a means to reduce fatigue are understudied. This qualitative study explored the experience of adding a family component to a multimodal group intervention for fatigue. Data were collected from group observations, in-depth interviews, and debriefing sessions with the program social worker. Fourteen survivors completed the family intervention (mean age 57 years) with a family member or close friend. Four themes associated with the family intervention were identified: (a) importance of family inclusion, (b) education of family members about fatigue,

Genome-wide association study of survival in patients with pancreatic adenocarcinoma.

BACKGROUND AND OBJECTIVE: Survival of patients with pancreatic adenocarcinoma is limited and few prognostic factors are known. We conducted a two-stage genome-wide association study (GWAS) to identify germline variants associated with survival in patients with pancreatic adenocarcinoma. METHODS: We analysed overall survival in relation to single nucleotide polymorphisms (SNPs) among 1005 patients from two large GWAS datasets, PanScan I and ChinaPC. Cox proportional hazards regression was used in an additive genetic model with adjustment for age, sex, clinical stage and the top four principal components of population stratification. The first stage included 642 cases of European ancestry (PanScan), from which the top SNPs (p≤10(-5)) were advanced to a joint analysis with 363 additional patients from China (ChinaPC). RESULTS: In the first stage of cases of European descent, the top-ranked loci were at chromosomes 11p15.4, 18p11.21 and 1p36.13, tagged by rs12362504 (p=1.63×10(-7)), rs981621 (p=1.65×10(-7)) and rs16861827 (p=3.75×10(-7)), respectively. 131 SNPs with p≤10(-5) were advanced to a joint analysis with cases from the ChinaPC study. In the joint analysis, the top-ranked SNP was rs10500715 (minor allele frequency, 0.37; p=1.72×10(-7)) on chromosome 11p15.4, which is intronic to the SET binding factor 2 (SBF2) gene. The HR (95% CI) for death was 0.74 (0.66 to 0.84) in PanScan I, 0.79 (0.65 to 0.97) in ChinaPC and 0.76 (0.68 to 0.84) in the joint analysis. CONCLUSIONS: Germline genetic variation in the SBF2 locus was associated with overall survival in patients with pancreatic adenocarcinoma of European and Asian ancestry. This association should be investigated in additional large patient cohorts.

Association between race and physical functioning limitations among breast cancer survivors.

PURPOSE: The goal of this study was to examine differences in physical functioning limitations among African-American and white breast cancer survivors. METHODS: Data were analyzed from 115 African-American and 712 white breast cancer survivors who responded to a hospital registry-based survey. Physical functioning limitations were assessed using a series of eight questions in which individuals were asked about their ability to perform a physical task such as walking a quarter of a mile. A four-category summary score, representing overall severity of limitation, was created using participant responses to the eight questions. Ordinal logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (CI) for the association between race and physical functioning limitation adjusted for potential confounders. RESULTS: In the unadjusted model, the African-American breast cancer survivors were more than twice as likely to have a greater degree of physical functioning limitation compared to their white counterparts (OR 2.31; 95% CI 1.59, 3.38). After adjustment for covariates, including body mass index (BMI), the race OR was attenuated and no longer statistically significant (OR 1.44; 95% CI 0.92, 2.27). CONCLUSIONS: Findings from this study showed that African-American breast cancer survivors were more likely to have worse physical functioning limitations than their white counterparts; however, much of this disparity was due to racial differences in other variables such as BMI. Future research should focus on effective interventions targeting modifiable risk factors of physical functioning limitations among breast cancer survivors with the goal of improving quality of life.

Choosing Wisely: Applying Value-Based Economic Principles to Population Science Research Investment.

Scientific research requires a substantial investment of time, effort, and money by researchers and funders. The funding that would be needed for all meritorious proposals far exceeds available resources. Major funding organizations use a multistep process for allocating research dollars that follows and extends beyond scientific peer review with considerations including mission priority, budget, and potential duplication of past or ongoing research activities. At the level of programmatic review, the process tends to be less proscribed than scientific review, but considerations relate to and are akin to basic value-driven economic principles. We propose a framework that encompasses the elements of programmatic review and provide examples of how the economic principles of opportunity costs, diminishing marginal productivity, sunk costs, economic optimization, return on investment, and option value apply to both research planning and funding decisions. Examples use cancer control population science research, as the nature of observational and interventional research involves large population studies (large sample size, recruitment, and often long-duration follow-up costs) which demand a high level of resource utilization; the same principles can be applied throughout medical and population health research. Awareness of the aspects of programmatic review and context to focus discussion regarding funding decisions may help guide research planning, decision-making, and increase transparency of the overall review process.

DNA repair gene variants in relation to overall cancer risk: a population-based study.

The hypothesis that germ-line polymorphisms in DNA repair genes influence cancer risk has previously been tested primarily on a cancer site-specific basis. The purpose of this study was to test the hypothesis that DNA repair gene allelic variants contribute to globally elevated cancer risk by measuring associations with risk of all cancers that occurred within a population-based cohort. In the CLUE II cohort study established in 1989 in Washington County, MD, this study was comprised of all 3619 cancer cases ascertained through 2007 compared with a sample of 2296 with no cancer. Associations were measured between 759 DNA repair gene single nucleotide polymorphisms (SNPs) and risk of all cancers. A SNP in O(6)-methylguanine-DNA methyltransferase, MGMT, (rs2296675) was significantly associated with overall cancer risk [per minor allele odds ratio (OR) 1.30, 95% confidence interval (CI) 1.19-1.43 and P-value: 4.1 × 10(-8)]. The association between rs2296675 and cancer risk was stronger among those aged ≤54 years old than those who were ≥55 years at baseline (P-for-(interaction) = 0.021). OR were in the direction of increased risk for all 15 categories of malignancies studied (P < 0.0001), ranging from 1.22 (P = 0.42) for ovarian cancer to 2.01 (P = 0.008) for urinary tract cancers; the smallest P-value was for breast cancer (OR 1.45, P = 0.0002). The results indicate that the minor allele of MGMT SNP rs2296675, a common genetic marker with 37% carriers, was significantly associated with increased risk of cancer across multiple tissues. Replication is needed to more definitively determine the scientific and public health significance of this observed association.

Aromatase inhibitor therapy and hair loss among breast cancer survivors.

The objective of this study was to examine the associations between aromatase inhibitor therapy and hair loss or hair thinning among female breast cancer survivors. Data were analyzed from 851 female breast cancer survivors who responded to a hospital registry-based survey. Data on hair loss, hair thinning, demographic characteristics, and health habits were based on self-report; data on aromatase inhibitor therapy were collected on the survey and verified using medical record review. Logistic regression was used to estimate the odds ratios (ORs) and 95 % confidence intervals (CIs) for the associations between aromatase inhibitor therapy and the hair outcome variables adjusted for potential confounders, including age and chemotherapy treatment. The results showed that 22.4 % of the breast cancer survivors reported hair loss and 31.8 % reported hair thinning. In the confounder-adjusted analyses, breast cancer survivors who were within 2 years of starting aromatase inhibitor treatment at the time of survey completion were approximately two and a half times more likely to report reporting hair loss (OR 2.55; 95 % CI 1.19-5.45) or hair thinning (OR 2.33; 95 % CI 1.10-4.93) within the past 4 weeks compared to those who were never treated with an aromatase inhibitor. Current aromatase inhibitor use for two or more years at the time of the survey and prior use were significantly associated with hair thinning (current users, ≥2 years: OR 1.86; prior users: OR 1.62), but not hair loss. Findings from this study suggest that aromatase inhibitor use is associated with an increased risk of hair loss and hair thinning independent of chemotherapy and age; these side effects are likely due to the substantial decrease in estrogen concentrations resulting from treatment with this drug. Future research should focus on examining these associations in a prospective manner using more detailed and objective measures of hair loss and thinning.