The associations between intake of or circulating fatty acids and risk of colorectal cancer (CRC) are unclear. We examined prospectively the associations between dietary or biomarker fatty acids and ...CRC. For 41,514 men and women, aged 40–69 years, baseline (1990–94) dietary intakes of fatty acids were estimated using a food frequency questionnaire and plasma phospholipid (PPL) fatty acids were measured for 4,205 participants including 395 CRC cases, according to a case‐cohort design. Hazard ratios were computed using Cox regression adjusting for education, alcohol intake, smoking status, physical activity and total energy intake; and stratified for gender, ethnicity and family history of cancer, with age as the time scale. We assessed the heterogeneity of associations with colon and rectal cancers. PPL saturated fatty acids (SFAs) were positively associated with CRC risk, while total n‐3 polyunsaturated fatty acids (PUFA) and long chain marine n‐3 PUFAs showed inverse associations, significant only for 22:5 n‐3. No significant associations were observed for dietary fatty acid intakes but positive associations with CRC of borderline significance were seen for both dietary and PPL linoleic acid. Positive associations with dietary palmitic acid (16:0), MUFAs and n‐6 PUFAs were seen for rectal but not colon cancers. PPL 22:6 n‐3 was inversely associated with rectal cancer. Limiting intakes of SFAs and MUFAs could be assisted by following existing guidelines to limit red and processed meats which are important sources in the Australian diet. Our observations regarding linoleic acid should be examined further.
What's new?
While there is considerable evidence that diet is associated with colorectal cancer (CRC) risk, the associations for specific fatty acids remain unclear. Here, the authors prospectively examine associations between dietary intake estimates or plasma phospholipids (PPL) estimates of fatty acids and incident CRC. PPL saturated fat (SF) is positively associated with incident CRC and dietary SF with rectal cancer, while long chain n‐3 fats are inversely associated with both. Following guidelines to limit red and processed meat would help reduce saturated fatty acids intake; the adverse association with linoleic acid, found in margarines and vegetable oils, requires further confirmation.
Summary
Background
Melanoma aetiology has been proposed to have two pathways, which are determined by naevi and type of sun exposure and related to the anatomical site where melanoma develops.
...Objectives
We examined associations with melanoma by anatomical site for a comprehensive set of risk factors including pigmentary and naevus phenotypes, ultraviolet radiation exposure and polygenic risk.
Methods
We analysed harmonized data from 2617 people with incident first invasive melanoma and 975 healthy controls recruited through two population‐based case–control studies in Australia and the UK. Questionnaire data were collected by interview using a single protocol, and pathway‐specific polygenic risk scores were derived from DNA samples. We estimated adjusted odds ratios using unconditional logistic regression that compared melanoma cases at each anatomical site with all controls.
Results
When cases were compared with control participants, there were stronger associations for many naevi vs. no naevi for melanomas on the trunk, and upper and lower limbs than on the head and neck (P‐heterogeneity < 0·001). Very fair skin (vs. olive/brown skin) was more weakly related to melanoma on the trunk than to melanomas at other sites (P‐heterogeneity = 0·04). There was no significant difference by anatomical site for polygenic risk. Increased weekday sun exposure was positively associated with melanoma on the head and neck but not on other sites.
Conclusions
We found evidence of aetiological heterogeneity for melanoma, supporting the dual pathway hypothesis. These findings enhance understanding of risk factors for melanoma and can guide prevention and skin examination education and practices.
What is already known about this topic?
Two main biological pathways have been proposed for the aetiology of melanoma – determined by naevi and type of sun exposure and related to the anatomical site at which melanoma develops.
Risk factors for melanoma may differ by anatomical site, but analyses are often limited by study sample size and most have focused on sun exposure.
What does this study add?
This study provides an examination of a comprehensive set of risk factors for melanoma by anatomical site, using a harmonized dataset from two population‐based studies with 3592 participants.
The presence of increased numbers of naevi was more strongly associated with melanomas on the trunk and limbs than on the head and neck.
Very fair skin was more weakly related to melanoma on the trunk than on other sites.
The association of pathway‐specific polygenic risk scores with melanoma did not differ by anatomical site.
Linked Comment: Ghiasvand. Br J Dermatol 2021; 184:995–996.
Reported associations between protein intake from different sources and type 2 diabetes (T2D) have been inconsistent.
We prospectively examined the relations of total, animal, and plant protein ...intakes with incident T2D.
We followed 21,523 participants (women: 61.7%) between 1990 and 2007 from the Melbourne Collaborative Cohort Study who were free of diabetes, cardiovascular disease, cancer, and kidney stones at baseline. We also conducted a meta-analysis that included the results from our cohort and from 10 previous prospective studies.
A total of 929 new cases (4.3%) of T2D were documented during a mean of 11.7 y of follow-up. Multivariate-adjusted ORs for incident T2D in the highest compared with lowest quintiles of total and animal protein intakes as percentages of energy were 1.23 (95% CI: 0.96, 1.56; P-trend = 0.029) and 1.29 (95% CI: 0.99, 1.67; P-trend = 0.014), respectively. These associations appeared to be greater in men and in participants with normal baseline plasma glucose, body mass index, or blood pressure. Plant protein intake was inversely associated with incident T2D in women only (OR; 0.60; 95% CI: 0.37, 0.99). In the meta-analysis of 11 prospective cohort studies with 505,624 participants and 37,918 T2D cases (follow-up range: 5-24 y), pooled RRs for the comparison of the highest with lowest categories of total, animal, and plant protein intakes were 1.09 (95% CI: 1.06, 1.13), 1.19 (95% CI: 1.11, 1.28), and 0.95 (95% CI: 0.89, 1.02), respectively. Associations between animal protein intake and T2D were similar across sex, geographic region, length of follow-up, study quality, and method of expressing protein intake. An inverse association between plant protein intake and T2D was observed in women (RR: 0.93; 95% CI: 0.85, 1.00) and in US populations (RR: 0.91; 95% CI: 0.84, 0.97).
Higher intakes of total and animal protein were both associated with increased risks of T2D, whereas higher plant protein intake tended to be associated with lower risk of T2D.
Differences in cancer survival by sex Afshar, Nina; English, Dallas R.; Thursfield, Vicky ...
Cancer causes & control,
11/2018, Volume:
29, Issue:
11
Journal Article
Peer reviewed
Purpose
Few large-scale studies have investigated sex differences in cancer survival and little is known about their temporal and age-related patterns.
Methods
We used cancer registry data for first ...primary cancers diagnosed between 1982 and 2015 in Victoria, Australia. Cases were followed until the end of 2015 through linkage to death registries. Differences in survival were assessed for 25 cancers using the Pohar-Perme estimator of net survival and the excess mortality rate ratio (EMRR) adjusting for age and year of diagnosis.
Results
Five-year net survival for all cancers combined was lower for men (47.1%; 95% CI 46.9–47.4) than women (52.0%; 95% CI 51.7–52.3); EMRR 1.13 (95% CI 1.12–1.14;
p
< 0.001). A survival disadvantage for men was observed for 11 cancers: head and neck, esophagus, colorectum, pancreas, lung, bone, melanoma, mesothelioma, kidney, thyroid, and non-Hodgkin lymphoma. In contrast, women had lower survival from cancers of the bladder, renal pelvis, and ureter. For the majority of cancers with survival differences, the EMRR decreased with increasing age at diagnosis; for colorectal, esophageal, and kidney cancer, the EMRR increased with time since diagnosis.
Conclusion
Identifying the underlying reasons behind sex differences in cancer survival is necessary to address inequalities, which may improve outcomes for men and women.
To examine the risk of total knee arthroplasty (TKA) due to osteoarthritis associated with obesity defined by body mass index (BMI) or waist circumference (WC) and whether there is discordance ...between these measures in assessing this risk.
36,784 participants from the Melbourne Collaborative Cohort Study with BMI and WC measured at 1990-1994 were included. Obesity was defined by BMI (≥30 kg/m2) or WC (men ≥102cm, women ≥88cm). The incidence of TKA between January 2001 and December 2018 was determined by linking participant records to the National Joint Replacement Registry.
Over 15.4±4.8 years, 2,683 participants underwent TKA. There were 20.4% participants with BMI-defined obesity, 20.8% with WC-defined obesity, and 73.6% without obesity defined by either BMI or WC. Obesity was classified as non-obese (misclassified obesity) in 11.7% of participants if BMI or WC alone was used to define obesity. BMI-defined obesity (HR 2.69, 95%CI 2.48-2.92), WC-defined obesity (HR 2.28, 95%CI 2.10-2.48), and obesity defined by either BMI or WC (HR 2.53, 95%CI 2.33-2.74) were associated with an increased risk of TKA. Compared with those without obesity, participants with misclassified obesity had an increased risk of TKA (HR 2.06, 95%CI 1.85-2.30). 22.7% of TKA in the community can be attributable to BMI-defined obesity, and a further 3.3% of TKA can be identified if WC was also used to define obesity.
Both BMI and WC should be used to identify obese individuals who are at risk of TKA for osteoarthritis and should be targeted for prevention and treatment.
The heterogeneity among colorectal tumors is probably due to differences in developmental pathways and might associate with patient survival times. We studied the relationship among markers of ...different subtypes of colorectal tumors and patient survival.
We pooled data from 7 observational studies, comprising 5010 patients with colorectal cancer. All the studies collected information on microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and mutations in KRAS and BRAF in tumors. Tumors with complete marker data were classified as type 1 (MSI-high, CIMP-positive, with pathogenic mutations in BRAF but not KRAS), type 2 (not MSI-high, CIMP-positive, with pathogenic mutations in BRAF but not KRAS), type 3 (not MSI-high or CIMP, with pathogenic mutations in KRAS but not BRAF), type 4 (not MSI-high or CIMP, no pathogenic mutations in BRAF or KRAS), or type 5 (MSI-high, no CIMP, no pathogenic mutations in BRAF or KRAS). We used Cox regression to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for associations of these subtypes and tumor markers with disease-specific survival (DSS) and overall survival times, adjusting for age, sex, stage at diagnosis, and study population.
Patients with type 2 colorectal tumors had significantly shorter time of DSS than patients with type 4 tumors (HRDSS 1.66; 95% CI 1.33–2.07), regardless of sex, age, or stage at diagnosis. Patients without MSI-high tumors had significantly shorter time of DSS compared with patients with MSI-high tumors (HRDSS 0.42; 95% CI 0.27–0.64), regardless of other tumor markers or stage, or patient sex or age.
In a pooled analysis of data from 7 observational studies of patients with colorectal cancer, we found that tumor subtypes, defined by combinations of 4 common tumor markers, were associated with differences in survival time. Colorectal tumor subtypes might therefore be used in determining patients’ prognoses.
Alcohol consumption is an established risk factor for colorectal cancer (CRC). However, while studies have consistently reported elevated risk of CRC among heavy drinkers, associations at moderate ...levels of alcohol consumption are less clear. We conducted a combined analysis of 16 studies of CRC to examine the shape of the alcohol–CRC association, investigate potential effect modifiers of the association, and examine differential effects of alcohol consumption by cancer anatomic site and stage. We collected information on alcohol consumption for 14,276 CRC cases and 15,802 controls from 5 case‐control and 11 nested case‐control studies of CRC. We compared adjusted logistic regression models with linear and restricted cubic splines to select a model that best fit the association between alcohol consumption and CRC. Study‐specific results were pooled using fixed‐effects meta‐analysis. Compared to non‐/occasional drinking (≤1 g/day), light/moderate drinking (up to 2 drinks/day) was associated with a decreased risk of CRC (odds ratio OR: 0.92, 95% confidence interval CI: 0.88–0.98, p = 0.005), heavy drinking (2–3 drinks/day) was not significantly associated with CRC risk (OR: 1.11, 95% CI: 0.99–1.24, p = 0.08) and very heavy drinking (more than 3 drinks/day) was associated with a significant increased risk (OR: 1.25, 95% CI: 1.11–1.40, p < 0.001). We observed no evidence of interactions with lifestyle risk factors or of differences by cancer site or stage. These results provide further evidence that there is a J‐shaped association between alcohol consumption and CRC risk. This overall pattern was not significantly modified by other CRC risk factors and there was no effect heterogeneity by tumor site or stage.
What's new?
Heavy drinking is associated with increased colorectal cancer (CRC) risk, but there's debate about the impact of moderate drinking. Here, the authors conducted a combined analysis of 16 studies comprising 14,276 cases and 15,802 controls. By their analysis, drinking 1‐2 alcoholic beverages per day was associated with a reduced risk of CRC, compared with rare or no alcohol consumption. With 3 or more drinks per day, CRC risk rises. The authors suggest that moderate alcohol consumption may reduce inflammation and DNA damage, although they acknowledge that more research is needed to understand the biochemical mechanism at work.
Reports relating meat intake to prostate cancer risk are inconsistent. Associations between these dietary factors and prostate cancer were examined in a consortium of 15 cohort studies. During ...follow‐up, 52,683 incident prostate cancer cases, including 4,924 advanced cases, were identified among 842,149 men. Cox proportional hazard models were used to calculate study‐specific relative risks (RR) and then pooled using random effects models. Results do not support a substantial effect of total red, unprocessed red and processed meat for all prostate cancer outcomes, except for a modest positive association for tumors identified as advanced stage at diagnosis (advanced(r)). For seafood, no substantial effect was observed for prostate cancer regardless of stage or grade. Poultry intake was inversely associated with risk of advanced and fatal cancers (pooled multivariable RR MVRR, 95% confidence interval, comparing ≥45 vs. <5 g/day: advanced 0.83, 0.70–0.99; trend test p value 0.29), fatal, 0.69, 0.59–0.82, trend test p value 0.16). Participants who ate ≥25 versus <5 g/day of eggs (1 egg ∼ 50 g) had a significant 14% increased risk of advanced and fatal cancers (advanced 1.14, 1.01–1.28, trend test p value 0.01; fatal 1.14, 1.00–1.30, trend test p value 0.01). When associations were analyzed separately by geographical region (North America vs. other continents), positive associations between unprocessed red meat and egg intake, and inverse associations between poultry intake and advanced, advanced(r) and fatal cancers were limited to North American studies. However, differences were only statistically significant for eggs. Observed differences in associations by geographical region warrant further investigation.
What's New?
The debate over red meat consumption and cancer risk is longstanding. In this consortium of 15 cohorts from North America, Europe, Australia and Asia, the authors examined over 50,000 cases of prostate cancer and the associated intake of unprocessed red and processed meat, seafood, eggs and poultry. Overall no substantial risk for unprocessed red and processed meat intake and prostate cancer was found. Interestingly, positive associations between intake of unprocessed red meat as well as eggs and advanced or fatal prostate cancers were detected only in participants living in North America, a finding which warrants further investigation into meat and egg composition, consumption and potential differences in lifestyle and screening practices between continents.
So far, two genes associated with familial melanoma have been identified, accounting for a minority of genetic risk in families. Mutations in CDKN2A account for approximately 40% of familial cases, ...and predisposing mutations in CDK4 have been reported in a very small number of melanoma kindreds. Here we report the whole-genome sequencing of probands from several melanoma families, which we performed in order to identify other genes associated with familial melanoma. We identify one individual carrying a novel germline variant (coding DNA sequence c.G1075A; protein sequence p.E318K; rs149617956) in the melanoma-lineage-specific oncogene microphthalmia-associated transcription factor (MITF). Although the variant co-segregated with melanoma in some but not all cases in the family, linkage analysis of 31 families subsequently identified to carry the variant generated a log of odds (lod) score of 2.7 under a dominant model, indicating E318K as a possible intermediate risk variant. Consistent with this, the E318K variant was significantly associated with melanoma in a large Australian case-control sample. Likewise, it was similarly associated in an independent case-control sample from the United Kingdom. In the Australian sample, the variant allele was significantly over-represented in cases with a family history of melanoma, multiple primary melanomas, or both. The variant allele was also associated with increased naevus count and non-blue eye colour. Functional analysis of E318K showed that MITF encoded by the variant allele had impaired sumoylation and differentially regulated several MITF targets. These data indicate that MITF is a melanoma-predisposition gene and highlight the utility of whole-genome sequencing to identify novel rare variants associated with disease susceptibility.
An improved model for risk stratification can be useful for guiding public health strategies of breast cancer prevention.
To evaluate combined risk stratification utility of common low penetrant ...single nucleotide polymorphisms (SNPs) and epidemiologic risk factors.
Using a total of 17 171 cases and 19 862 controls sampled from the Breast and Prostate Cancer Cohort Consortium (BPC3) and 5879 women participating in the 2010 National Health Interview Survey, a model for predicting absolute risk of breast cancer was developed combining information on individual level data on epidemiologic risk factors and 24 genotyped SNPs from prospective cohort studies, published estimate of odds ratios for 68 additional SNPs, population incidence rate from the National Cancer Institute-Surveillance, Epidemiology, and End Results Program cancer registry and data on risk factor distribution from nationally representative health survey. The model is used to project the distribution of absolute risk for the population of white women in the United States after adjustment for competing cause of mortality.
Single nucleotide polymorphisms, family history, anthropometric factors, menstrual and/or reproductive factors, and lifestyle factors.
Degree of stratification of absolute risk owing to nonmodifiable (SNPs, family history, height, and some components of menstrual and/or reproductive history) and modifiable factors (body mass index BMI; calculated as weight in kilograms divided by height in meters squared, menopausal hormone therapy MHT, alcohol, and smoking).
The average absolute risk for a 30-year-old white woman in the United States developing invasive breast cancer by age 80 years is 11.3%. A model that includes all risk factors provided a range of average absolute risk from 4.4% to 23.5% for women in the bottom and top deciles of the risk distribution, respectively. For women who were at the lowest and highest deciles of nonmodifiable risks, the 5th and 95th percentile range of the risk distribution associated with 4 modifiable factors was 2.9% to 5.0% and 15.5% to 25.0%, respectively. For women in the highest decile of risk owing to nonmodifiable factors, those who had low BMI, did not drink or smoke, and did not use MHT had risks comparable to an average woman in the general population.
This model for absolute risk of breast cancer including SNPs can provide stratification for the population of white women in the United States. The model can also identify subsets of the population at an elevated risk that would benefit most from risk-reduction strategies based on altering modifiable factors. The effectiveness of this model for individual risk communication needs further investigation.
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