Publications by authors named "Polly A Newcomb"

Menopausal users of hormone replacement therapy (HRT) are at increased breast cancer risk and decreased colorectal cancer (CRC) risk compared with individuals who have never used HRT, but these opposing associations may differ by familial risk of breast cancer and CRC. We harmonized data from 3 cohorts and generated separate breast cancer and CRC familial risk scores based on cancer family history. We defined moderate or strong family history as a risk score of 0.

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Advancement of AI has opened new possibility for accurate diagnosis and prognosis using digital histopathology slides which not only saves hours of expert effort but also makes the estimation more standardized and accurate. However, preserving the AI model performance on the external sites is an extremely challenging problem in the histopathology domain which is primarily due to the difference in data acquisition and/or sampling bias. Although, AI models can also learn spurious correlation, they provide unequal performance across validation population.

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  • Colorectal cancer (CRC) is a major health concern, and understanding how genetic and environmental factors interact can help identify at-risk groups.
  • This study analyzed data from over 45,000 CRC cases to assess both multiplicative and additive interactions between genetic risk scores and various environmental factors, finding no multiplicative interactions but significant additive ones for high genetic susceptibility individuals.
  • Results suggest that individuals with high genetic risk could benefit more from lifestyle interventions like reducing alcohol intake or increasing fruit and fiber consumption, emphasizing the need for targeted prevention strategies in CRC care.
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  • The legal environment for cannabis has shifted, with more states allowing its use, particularly among cancer patients for alleviating treatment side effects.
  • A survey conducted across 12 cancer centers found that 32.9% of recently diagnosed cancer patients reported using cannabis, with varying rates based on state laws.
  • Common perceived benefits included relief from pain, sleep issues, and anxiety, though only 21.5% felt comfortable discussing their cannabis use with healthcare providers, despite the majority feeling at ease talking about it overall.
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Medical cannabis with cancer as a qualifying condition has become legalized in more states, but currently there are no standardized measures of perceived benefits and harms of cannabis use in cancer. This study surveyed a population-based sample of cancer survivors (n = 1539) with various types of cancer including breast (25%), prostate (17%), and gastrointestinal (11%) cancers. Item response theory analyses were used to evaluate the items for measuring perceived benefits and harms.

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  • * Researchers analyzed data from 52 studies, including nearly 31,000 CRC cases and over 41,000 controls, to explore the genetic interactions with regular aspirin/NSAID use.
  • * They found significant interactions with genetic variants in two specific regions (6q24.1 and 5p13.1), which could help uncover new targets for understanding how aspirin provides its protective effects against colorectal cancer.
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  • Colorectal cancer (CRC) is a widely increasing disease linked to high body mass index (BMI), but the exact biological processes connecting these two factors are not well understood.
  • The study employed Mendelian randomization to explore various biomarkers and lifestyle factors potentially mediating the impact of BMI on CRC risk, focusing on elements like inflammation, insulin levels, and physical activity.
  • The findings indicated that higher genetically predicted BMI correlates with increased CRC risk, with evidence suggesting that the relationship might be partly mediated by plasma IGF1, while smoking and physical activity appear to complicate the association rather than mediate it.
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Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV.

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  • Menopausal hormone therapy (MHT) may lower the risk of colorectal cancer (CRC), especially in women with a higher genetic predisposition to the disease.
  • In a study of nearly 30,000 postmenopausal women, those in the highest genetic risk quartile saw a significantly greater reduction in CRC risk when using MHT compared to those in the lowest quartile.
  • The findings suggest that integrating genetic risk information could improve CRC risk predictions and inform the assessment of MHT benefits in postmenopausal women.
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Purpose: This study aimed to characterize the prevalence and correlates of cannabis use and the methods and reasons for use among recently diagnosed cancer survivors in a population sample within Washington state.

Methods: We identified individuals diagnosed with invasive cancers in the prior 6 to 17 months from April 2020 to December 2020 using the Seattle-Puget Sound Surveillance, Epidemiology, and End Results (SEER) cancer registry. Participants (n = 1,515) completed a questionnaire, including demographics, medical history, cannabis use, and other substance use.

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  • Obesity is linked to various types of colorectal cancer (CRC), but the strength and cause of these links are not fully understood.
  • By using Mendelian randomization, researchers studied how body size traits like BMI, waist circumference, and body fat percentage affect risks for different CRC subtypes.
  • Results showed that higher BMI and body fat significantly increased the risks for serrated and alternate CRC pathways (Jass types 1, 2, and 3), while associations with the traditional pathway (Jass type 4) were weaker.
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We aimed to evaluate differences in dietary factors between young-onset (diagnosed at ages <50) and older-onset colorectal cancer (CRC). CRC patients diagnosed from 1998 to 2018 reported to the Puget Sound Surveillance, Epidemiology, and End Results registry were recruited using mail and telephone. Consented patients completed questionnaires assessing demographics, medical history, and CRC risk factors, including dietary factors.

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Background: Signs and red flag symptoms in colorectal cancer (CRC) patients who are below the recommended screening age are often overlooked, leading to delayed diagnosis and worse prognosis. This study investigates how patient pre-diagnostic symptoms are associated with anatomic site of their cancer and whether the association varies by age at CRC diagnosis.

Methods: We ascertained CRC patients' experienced symptoms and screening through medical abstractions from an ongoing population-based study of CRC patients identified through a SEER cancer registry (N = 626).

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Background: Tumour-promoting inflammation is a "hallmark" of cancer and conventional epidemiological studies have reported links between various inflammatory markers and cancer risk. The causal nature of these relationships and, thus, the suitability of these markers as intervention targets for cancer prevention is unclear.

Methods: We meta-analysed 6 genome-wide association studies of circulating inflammatory markers comprising 59,969 participants of European ancestry.

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Background: Alcohol is a risk factor for cancer and may pose unique risks for cancer survivors. Population-based studies of confirmed cancer cases are needed to estimate the extent of drinking among cancer survivors and to understand which survivors are most at risk of alcohol-related health problems.

Methods: Cancer survivors who resided in the Puget Sound Surveillance, Epidemiology, and End Results (SEER) region, were ages 21 to 74 years at diagnosis, and were 6 to 17 months post-diagnosis at the start of the recruitment period (April 2020-December 2020) were sent a survey that included demographics, substance use, mental health, and cancer-related items.

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Background: Type 2 diabetes is associated with higher risk of several cancer types. However, the biological intermediates driving this relationship are not fully understood. As novel interventions for treating and managing type 2 diabetes become increasingly available, whether they also disrupt the pathways leading to increased cancer risk is currently unknown.

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  • The genotoxin colibactin is linked to a specific mutation signature in colorectal cancer (SBS88), affecting tumor characteristics and possibly influencing risk and survival outcomes.
  • A study involving over 4,300 tumors found that higher fruit intake lowers the risk of SBS88-positive colorectal cancer, and some epidemiological factors like BMI and alcohol consumption show different associations based on the presence of SBS88.
  • While most risk and survival factors were similar regardless of SBS88 status, higher BMI might lead to worse survival outcomes for those with SBS88, suggesting a need for further research with more comprehensive genetic data.
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  • High consumption of red and processed meats is linked to an increased risk of colorectal cancer, with a study analyzing data from over 29,000 cancer cases and 39,000 control subjects confirming this association.
  • The research identified two significant genetic markers (SNPs) that interact with meat consumption levels, suggesting that certain genetic variants can influence individual cancer risk based on dietary habits.
  • These findings highlight the potential for using genetic information to better understand colorectal cancer risks related to diet, which may lead to personalized dietary recommendations for specific population subgroups.
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Background: The association of fitness with cancer risk is not clear.

Methods: We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of lung, colorectal, endometrial, breast, and prostate cancer in a subset of UK Biobank participants who completed a submaximal fitness test in 2009-12 (N = 72,572). We also investigated relationships using two-sample Mendelian randomisation (MR), odds ratios (ORs) were estimated using the inverse-variance weighted method.

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  • Polygenic risk scores (PRS) can help identify individuals at higher risk for colorectal cancer (CRC), but current models based on European ancestry data don't perform well for non-European populations.
  • A study expands PRS development by adding Asian ancestry data alongside European data, resulting in improved predictive accuracy across diverse racial and ethnic groups in the US.
  • The findings emphasize the need for including more non-European ancestry populations to enhance risk prediction and ensure equitable clinical application of PRS in CRC prevention.
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  • A study is exploring how genetic variations might influence the relationship between folate intake and colorectal cancer risk, focusing on specific genetic interactions.
  • The research analyzed data from over 30,000 colorectal cancer cases and 42,000 controls, examining the effects of dietary folate and folic acid supplements.
  • Results indicated that while higher folate intake is generally linked to lower CRC risk, certain genetic variants (like rs150924902) can modify this effect, with some genotypes showing increased risk with folate supplementation.
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We conducted the first large genome-wide association study to identify novel genetic variants that predict better (or poorer) prognosis in colorectal cancer patients receiving standard first-line oxaliplatin-based chemotherapy vs chemotherapy without oxaliplatin. We used data from two phase III trials, NCCTG N0147 and NCCTG N9741 and a population-based patient cohort, DACHS. Multivariable Cox proportional hazards models were employed, including an interaction term between each SNP and type of treatment for overall survival (OS) and progression-free survival.

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  • Diabetes is linked to a higher risk of colorectal cancer, but the mechanisms behind this link and the influence of genetic variants need further exploration.!* -
  • Researchers conducted a genome-wide analysis using data from over 31,000 colorectal cancer cases and nearly 41,500 controls to investigate gene-environment interactions involving genetics and diabetes.!* -
  • Findings revealed that specific genes on chromosomes 8q24.11 (SLC30A8) and 13q14.13 (LRCH1) may affect how diabetes increases colorectal cancer risk, highlighting potential biological pathways related to insulin signaling and immune functions.!*
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  • This study explores how genetics and body mass index (BMI) interact to influence colorectal cancer risk, analyzing data from over 84,000 participants.
  • The research identifies a significant genetic marker (rs58349661) in the FMN1/GREM1 gene region that shows a strong connection with increased cancer risk in individuals with higher BMI, particularly among those with a specific genotype.
  • Findings suggest that understanding this gene-environment interaction could help develop more tailored prevention strategies for colorectal cancer related to obesity.
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Background: Tumour-promoting inflammation is a "hallmark" of cancer and conventional epidemiological studies have reported links between various inflammatory markers and cancer risk. The causal nature of these relationships and, thus, the suitability of these markers as intervention targets for cancer prevention is unclear.

Methods: We meta-analysed 6 genome-wide association studies of circulating inflammatory markers comprising 59,969 participants of European ancestry.

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